Cochrane Database of Systematic Reviews
Mirtazapine versus other antidepressive agents for depression
(Review)
Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA
Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA.
Mirtazapine versus other antidepressive agents for depression.
Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No.: CD006528.
DOI: 10.1002/14651858.CD006528.pub2.
www.cochranelibrary.com
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 1.
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RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Figure 2.
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Figure 3.
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Figure 4.
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Figure 5.
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Figure 6.
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Figure 7.
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Figure 8.
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DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS
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REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 Mirtazapine versus TCAs, Outcome 1 Primary outcome (response) at 2 weeks. . . . .
Analysis 1.2. Comparison 1 Mirtazapine versus TCAs, Outcome 2 Primary outcome (response) at end of the acute-phase
treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.3. Comparison 1 Mirtazapine versus TCAs, Outcome 3 Secondary outcome (remission) at 2 weeks. . .
Analysis 1.4. Comparison 1 Mirtazapine versus TCAs, Outcome 4 Secondary outcome (remission) at end of the acutephase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.5. Comparison 1 Mirtazapine versus TCAs, Outcome 5 Secondary outcome (depression severity) at 2 weeks.
Analysis 1.6. Comparison 1 Mirtazapine versus TCAs, Outcome 6 Secondary outcome (depression severity) at end of the
acute-phase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.7. Comparison 1 Mirtazapine versus TCAs, Outcome 7 Secondary outcome (Social adjustment) at 2 weeks.
Analysis 1.8. Comparison 1 Mirtazapine versus TCAs, Outcome 8 Secondary outcome (Social adjustment) at end of the
acute-phase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.9. Comparison 1 Mirtazapine versus TCAs, Outcome 9 Secondary outcome (withdrawal due to any reason).
Analysis 1.10. Comparison 1 Mirtazapine versus TCAs, Outcome 10 Secondary outcome (withdrawal due to adverse
events). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.11. Comparison 1 Mirtazapine versus TCAs, Outcome 11 Secondary outcome (having some adverse events).
Analysis 1.12. Comparison 1 Mirtazapine versus TCAs, Outcome 12 Hypertension/Tachycardia. . . . . . . .
Analysis 1.13. Comparison 1 Mirtazapine versus TCAs, Outcome 13 Hypotension/Bradycardia. . . . . . . .
Analysis 1.14. Comparison 1 Mirtazapine versus TCAs, Outcome 14 Sweating. . . . . . . . . . . . . .
Analysis 1.15. Comparison 1 Mirtazapine versus TCAs, Outcome 15 Constipation. . . . . . . . . . . . .
Analysis 1.16. Comparison 1 Mirtazapine versus TCAs, Outcome 16 Dry mouth/Decreased salivation. . . . . .
Analysis 1.17. Comparison 1 Mirtazapine versus TCAs, Outcome 17 Nausea/Vomiting/Gastric distress. . . . . .
Analysis 1.18. Comparison 1 Mirtazapine versus TCAs, Outcome 18 Weight gain/Increased appetite. . . . . . .
Analysis 1.19. Comparison 1 Mirtazapine versus TCAs, Outcome 19 Sexual dysfunction. . . . . . . . . . .
Analysis 1.20. Comparison 1 Mirtazapine versus TCAs, Outcome 20 Anxiety/Agitation. . . . . . . . . . .
Analysis 1.21. Comparison 1 Mirtazapine versus TCAs, Outcome 21 Dizziness/Vertigo/Faintness. . . . . . . .
Analysis 1.22. Comparison 1 Mirtazapine versus TCAs, Outcome 22 Fatigue/Tiredness/Asthenia. . . . . . . .
Analysis 1.23. Comparison 1 Mirtazapine versus TCAs, Outcome 23 Headache. . . . . . . . . . . . . .
Analysis 1.24. Comparison 1 Mirtazapine versus TCAs, Outcome 24 Tremor. . . . . . . . . . . . . . .
Analysis 1.25. Comparison 1 Mirtazapine versus TCAs, Outcome 25 Sleep disturbance. . . . . . . . . . .
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Analysis 1.26. Comparison 1 Mirtazapine versus TCAs, Outcome 26 Sleepiness/Drowsiness/Somnolence. . . . .
Analysis 1.27. Comparison 1 Mirtazapine versus TCAs, Outcome 27 Suicide attempt. . . . . . . . . . . .
Analysis 1.28. Comparison 1 Mirtazapine versus TCAs, Outcome 28 Subgroup analysis: Response at 2 weeks: Treatment
settings: Psychiatric inpatients. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.29. Comparison 1 Mirtazapine versus TCAs, Outcome 29 Subgroup analysis: Response at end of the acute-phase
treatment: Treatment settings: Psychiatric inpatients. . . . . . . . . . . . . . . . . . . . .
Analysis 1.30. Comparison 1 Mirtazapine versus TCAs, Outcome 30 Sensitivity analysis: Response at 2 weeks: Studies
without imputation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.31. Comparison 1 Mirtazapine versus TCAs, Outcome 31 Sensitivity analysis: Response at end of the acutephase treatment: Studies without imputation. . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.1. Comparison 2 Mirtazapine versus SSRIs, Outcome 1 Primary outcome (response) at 2 weeks. . . . .
Analysis 2.2. Comparison 2 Mirtazapine versus SSRIs, Outcome 2 Primary outcome (response) at end of the acute-phase
treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.3. Comparison 2 Mirtazapine versus SSRIs, Outcome 3 Primary outcome (response) at end of the continuation
treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.4. Comparison 2 Mirtazapine versus SSRIs, Outcome 4 Secondary outcome (remission) at 2 weeks. . .
Analysis 2.5. Comparison 2 Mirtazapine versus SSRIs, Outcome 5 Secondary outcome (remission) at end of the acutephase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.6. Comparison 2 Mirtazapine versus SSRIs, Outcome 6 Secondary outcome (remission) at end of the
continuation treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.7. Comparison 2 Mirtazapine versus SSRIs, Outcome 7 Secondary outcome (withdrawal due to any reason).
Analysis 2.8. Comparison 2 Mirtazapine versus SSRIs, Outcome 8 Secondary outcome (withdrawal due to adverse
events). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.9. Comparison 2 Mirtazapine versus SSRIs, Outcome 9 Secondary outcome (having some adverse events).
Analysis 2.10. Comparison 2 Mirtazapine versus SSRIs, Outcome 10 Hypotension/Bradycardia. . . . . . . .
Analysis 2.11. Comparison 2 Mirtazapine versus SSRIs, Outcome 11 Sweating. . . . . . . . . . . . . .
Analysis 2.12. Comparison 2 Mirtazapine versus SSRIs, Outcome 12 Constipation. . . . . . . . . . . . .
Analysis 2.13. Comparison 2 Mirtazapine versus SSRIs, Outcome 13 Diarrhoea. . . . . . . . . . . . . .
Analysis 2.14. Comparison 2 Mirtazapine versus SSRIs, Outcome 14 Dry mouth/Decreased salivation. . . . . .
Analysis 2.15. Comparison 2 Mirtazapine versus SSRIs, Outcome 15 Nausea/Vomiting/Gastric distress. . . . . .
Analysis 2.16. Comparison 2 Mirtazapine versus SSRIs, Outcome 16 Weight gain/Increased appetite. . . . . . .
Analysis 2.17. Comparison 2 Mirtazapine versus SSRIs, Outcome 17 Weight loss/Anorexia. . . . . . . . . .
Analysis 2.18. Comparison 2 Mirtazapine versus SSRIs, Outcome 18 Sexual dysfunction. . . . . . . . . . .
Analysis 2.19. Comparison 2 Mirtazapine versus SSRIs, Outcome 19 Anxiety/Agitation. . . . . . . . . . .
Analysis 2.20. Comparison 2 Mirtazapine versus SSRIs, Outcome 20 Dizziness/Vertigo/Faintness. . . . . . . .
Analysis 2.21. Comparison 2 Mirtazapine versus SSRIs, Outcome 21 Fatigue/Tiredness/Asthenia. . . . . . . .
Analysis 2.22. Comparison 2 Mirtazapine versus SSRIs, Outcome 22 Headache. . . . . . . . . . . . . .
Analysis 2.23. Comparison 2 Mirtazapine versus SSRIs, Outcome 23 Tremor. . . . . . . . . . . . . . .
Analysis 2.24. Comparison 2 Mirtazapine versus SSRIs, Outcome 24 Sleep disturbance. . . . . . . . . . .
Analysis 2.25. Comparison 2 Mirtazapine versus SSRIs, Outcome 25 Sleepiness/Drowsiness/Somnolence. . . . .
Analysis 2.26. Comparison 2 Mirtazapine versus SSRIs, Outcome 26 Suicide attempt. . . . . . . . . . . .
Analysis 2.27. Comparison 2 Mirtazapine versus SSRIs, Outcome 27 Subgroup analysis: Response at 2 weeks: Treatment
settings: Outpatients in primary care. . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.28. Comparison 2 Mirtazapine versus SSRIs, Outcome 28 Subgroup analysis: Response at end of the acute-phase
treatment: Treatment settings: Outpatients in primary care. . . . . . . . . . . . . . . . . . .
Analysis 2.29. Comparison 2 Mirtazapine versus SSRIs, Outcome 29 Sensitivity analysis: Response at 2 weeks: Studies
without imputation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 2.30. Comparison 2 Mirtazapine versus SSRIs, Outcome 30 Sensitivity analysis: Response at end of the acutephase treatment: Studies without imputation. . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.1. Comparison 3 Mirtazapine versus SNRIs, Outcome 1 Primary outcome (response) at 2 weeks. . . .
Analysis 3.2. Comparison 3 Mirtazapine versus SNRIs, Outcome 2 Primary outcome (response) at end of the acute-phase
treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.3. Comparison 3 Mirtazapine versus SNRIs, Outcome 3 Secondary outcome (remission) at 2 weeks. . .
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Analysis 3.4. Comparison 3 Mirtazapine versus SNRIs, Outcome 4 Secondary outcome (remission) at end of the acutephase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.5. Comparison 3 Mirtazapine versus SNRIs, Outcome 5 Secondary outcome (withdrawal due to any reason).
Analysis 3.6. Comparison 3 Mirtazapine versus SNRIs, Outcome 6 Secondary outcome (withdrawal due to adverse
events). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 3.7. Comparison 3 Mirtazapine versus SNRIs, Outcome 7 Secondary outcome (having some adverse events).
Analysis 3.8. Comparison 3 Mirtazapine versus SNRIs, Outcome 8 Hypotension/Bradycardia. . . . . . . . .
Analysis 3.9. Comparison 3 Mirtazapine versus SNRIs, Outcome 9 Sweating. . . . . . . . . . . . . . .
Analysis 3.10. Comparison 3 Mirtazapine versus SNRIs, Outcome 10 Constipation.
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Analysis 3.11. Comparison 3 Mirtazapine versus SNRIs, Outcome 11 Dry mouth/Decreased salivation. . . . . .
Analysis 3.12. Comparison 3 Mirtazapine versus SNRIs, Outcome 12 Nausea/Vomiting/Gastric distress. . . . .
Analysis 3.13. Comparison 3 Mirtazapine versus SNRIs, Outcome 13 Anxiety/Agitation. . . . . . . . . . .
Analysis 3.14. Comparison 3 Mirtazapine versus SNRIs, Outcome 14 Fatigue/Tiredness/Asthenia. . . . . . . .
Analysis 3.15. Comparison 3 Mirtazapine versus SNRIs, Outcome 15 Headache. . . . . . . . . . . . . .
Analysis 3.16. Comparison 3 Mirtazapine versus SNRIs, Outcome 16 Sleep disturbance. . . . . . . . . . .
Analysis 3.17. Comparison 3 Mirtazapine versus SNRIs, Outcome 17 Sleepiness/Drowsiness/Somnolence. . . . .
Analysis 3.18. Comparison 3 Mirtazapine versus SNRIs, Outcome 18 Completed suicide. . . . . . . . . . .
Analysis 4.1. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 1 Primary outcome (response) at 2
weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.2. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 2 Primary outcome (response) at
end of the acute-phase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.3. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 3 Secondary outcome (remission) at
2 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.4. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 4 Secondary outcome (remission) at
end of the acute-phase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.5. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 5 Secondary outcome (withdrawal
due to any reason). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.6. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 6 Secondary outcome (withdrawal
due to adverse events). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.7. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 7 Hypertension/Tachycardia.
Analysis 4.8. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 8 Hypotension/Bradycardia. .
Analysis 4.9. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 9 Constipation. . . . . .
Analysis 4.10. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 10 Dry mouth/Decreased
salivation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.11. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 11 Nausea/Vomiting/Gastric
distress. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.12. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 12 Weight gain/Increased
appetite. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.13. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 13 Weight loss/Anorexia. .
Analysis 4.14. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 14 Anxiety/Agitation. . . .
Analysis 4.15. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 15 Dizziness/Vertigo/Faintness.
Analysis 4.16. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 16 Headache. . . . . .
Analysis 4.17. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 17 Sleep disturbance. . . .
Analysis 4.18. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 18 Sleepiness/Drowsiness/Somnolence. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 4.19. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 19 Completed suicide. . .
Analysis 4.20. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 20 Suicide attempt. . . .
Analysis 5.1. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 1 Primary outcome (response) at 2
weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 5.2. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 2 Primary outcome (response) at end of
the acute-phase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 5.3. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 3 Secondary outcome (remission) at 2
weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Mirtazapine versus other antidepressive agents for depression (Review)
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Analysis 5.4. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 4 Secondary outcome (remission) at end
of the acute-phase treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 5.5. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 5 Secondary outcome (depression severity)
at 2 weeks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 5.6. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 6 Secondary outcome (withdrawal due to
any reason). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 5.7. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 7 Secondary outcome (withdrawal due to
adverse events). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 6.1. Comparison 6 Funnel plot analysis: primary outcome (response) at end of the acute-phase treatment, Outcome
1 vs all compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
INDEX TERMS
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[Intervention Review]
Mirtazapine versus other antidepressive agents for depression
Norio Watanabe1 , Ichiro M Omori2 , Atsuo Nakagawa3 , Andrea Cipriani4 , Corrado Barbui4 , Rachel Churchill5 , Toshi A Furukawa6
1 Department
of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya,
Japan. 2 Department of Psychiatry, Toyokawa City Hospital, Aichi, Japan. 3 Department of Psychiatry, Keio University School of
Medicine, Tokyo, Japan. 4 Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology,
University of Verona, Verona, Italy. 5 Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol,
Bristol, UK. 6 Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of
Public Health, Kyoto, Japan
Contact address: Norio Watanabe, Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya City University Graduate
School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan. noriow@med.nagoya-cu.ac.jp.
Editorial group: Cochrane Common Mental Disorders Group.
Publication status and date: New, published in Issue 12, 2011.
Review content assessed as up-to-date: 1 July 2011.
Citation: Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA. Mirtazapine versus
other antidepressive agents for depression. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No.: CD006528. DOI:
10.1002/14651858.CD006528.pub2.
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT
Background
Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice.
Objectives
The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other
antidepressive agents in the acute-phase treatment of major depression in adults.
Search methods
We searched the Cochrane Collaboration Depression, Anxiety and Neurosis review group’s specialised register (CCDANCTR), which
includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to April
2011), EMBASE, (1980 to July 2011) MEDLINE (1950 to July 2011) and PsycINFO (1974 to July 2011). Reference lists of the
reports of relevant studies were checked and experts in the field contacted. The review was not limited to English-language articles.
Selection criteria
Randomised controlled trials (RCTs) allocating participants with major depression to mirtazapine versus any other antidepressive agent.
Data collection and analysis
Two authors independently checked eligibility and extracted data on an intention-to-treat basis. The primary outcome was response
to treatment. The secondary outcomes included dropouts and individual adverse events.
Meta-analyses were conducted using the random-effects model.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Main results
A total of 29 RCTs (n = 4974), mostly following up the participants for six weeks in outpatient clinics and inadequately reporting the
risk of bias, were included. In comparison with tricyclic antidepressants (10 trials, n = 1553) there was no robust evidence to detect a
difference between mirtazapine and tricyclics in terms of response at two weeks (odds ratio (OR) 0.85, 95% confidence interval (CI)
0.64 to 1.13) or at the end of acute-phase treatment (at 6 to 12 weeks) (OR 0.89, 95% CI 0.72 to 1.10). In comparison with selective
serotonin reuptake inhibitors (SSRIs) (12 trials, n = 2626) mirtazapine was significantly more effective at two weeks (OR 1.57, 95% CI
1.30 to 1.88) and at the end of acute-phase treatment (OR 1.19, 95% CI 1.01 to 1.39). Mirtazapine was significantly more effective
than a serotonin-noradrenaline reuptake inhibitor (venlafaxine only, two trials, n = 415) at two weeks (OR 2.29, 95% CI 1.45 to 3.59)
and at the end of acute-phase treatment (OR 1.53, 95% CI 1.03 to 2.25).
In terms of dropouts, there was no robust evidence to detect a difference between mirtazapine and other antidepressants. Mirtazapine
was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and
sexual dysfunction.
Authors’ conclusions
Some statistically significant and possibly clinically meaningful differences between mirtazapine and other antidepressive agents were
found for the acute-phase treatment of major depression. Mirtazapine is likely to have a faster onset of action than SSRIs during the
acute-phase treatment. Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants,
although the adverse event profile of mirtazapine is unique.
PLAIN LANGUAGE SUMMARY
Mirtazapine versus other antidepressive agents for depression
Major depression is characterised by a persistent low mood and loss of interest and pleasure. These symptoms are often accompanied
by loss of appetite, insomnia, fatigue, poor concentration, inappropriate guilty feelings and even suicide. Depression was the third
leading cause of disease burden among all diseases experienced by humankind in 2002. Antidepressants are used in treatment for major
depression. They are the mainstay of treatment. Among them, mirtazapine is known to have a unique pharmacological profile and thus
is supposed to differ in its efficacy and adverse effects profile in comparison with other antidepressants.
The evidence from this review, which included findings from 29 randomised controlled trials (4974 participants in total), suggests
that mirtazapine is likely to have a faster onset of action than the most frequently used type of antidepressants, which are the selective
serotonin reuptake inhibitors (SSRIs). It would appear that mirtazapine is superior to SSRIs at the end of treatment over 6 to 12 weeks.
Mirtazapine causes adverse events that lead to a similar frequency of dropouts as SSRIs and tricyclic antidepressants, although adverse
event profile of mirtazapine is unique. Mirtazapine is likely to cause weight gain or increased appetite and somnolence but is less likely
to cause nausea or vomiting and sexual dysfunction than SSRIs.
BACKGROUND
Description of the condition
Major depression is generally diagnosed in people with a persistent and unreactive low mood and loss of all interest and pleasure accompanied by a range of symptoms including appetite loss,
insomnia, fatigue, loss of energy, poor concentration, psychomo-
tor symptoms, inappropriate guilt and morbid thoughts of death
(APA 1994). It was the third leading cause of burden among all
diseases of humankind, after lower respiratory infections and HIV/
AIDS, in the year 2002 and accounted for 4.5% of total human
suffering (WHO 2006a). Moreover, it is expected to show a rising
trend during the coming 20 years (WHO 2006b). This condition
is associated with marked personal, social and economic morbidity, loss of functioning and productivity, and creates significant
demands on service providers in terms of workload (NICE 2004).
Mirtazapine versus other antidepressive agents for depression (Review)
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Description of the intervention
Although both pharmacological and psychological interventions
are effective for major depression, in primary and secondary
care settings antidepressant drugs remain the mainstay of treatment (APA 2000; Ellis 2004; NICE 2004). Amongst antidepressants many different agents are available, including tricyclics
(TCAs) (for example amitriptyline, amoxapine, clomipramine,
desipramine, dosulepin, doxepin, imipramine, nortriptyline),
monoamine oxidase inhibitors (MAOIs) (for example moclobemide, selegiline, tranylcypromine), selective serotonin reuptake inhibitors (SSRIs) (for example citalopram, escitalopram, fluoxetine,
fluvoxamine, paroxetine, sertraline), serotonin-noradrenaline reuptake inhibitors (SNRIs) (for example venlafaxine, duloxetine,
milnacipran) and other newer agents (mirtazapine, reboxetine,
bupropion).
In many western countries, antidepressant consumption has risen
dramatically during the last 20 years, mainly because of the increasing consumption of SSRIs and newer antidepressants that
have progressively become the most commonly prescribed antidepressants (Ciuna 2004; Guaiana 2005). SSRIs are generally better tolerated than TCAs (Barbui 2000; Hotopf 1997; Steffens
1997), and there is some evidence of similar efficacy (Anderson
2000; Williams 2000). However, head-to-head comparisons provide contrasting findings. Amitriptyline, for example, may have
the edge over SSRIs in terms of efficacy (Guaiana 2003) and individual SSRIs and SNRIs may differ in terms of efficacy and tolerability (Cipriani 2005; Puech 1997; Smith 2002).
Given that the most recently available evidence refers to the SSRIs
as a homogeneous group (Arroll 2005; Hansen 2005), it is still
unclear how each of the SSRIs or newer agents compare with other
antidepressants in terms of effects and side effects.
How the intervention might work
Mirtazapine is a prescription only antidepressant introduced in
1996. It has a unique pharmacological profile, including potent antagonism of central alpha 2-adrenergic autoreceptors and heteroreceptors and antagonism of both serotonin 5-hydroxytryptamine2 (5-HT2) and 5-HT3 receptors (Kent 2000). Unlike venlafaxine
and nefazodone, mirtazapine has minimum effects on monoamine
reuptake and is classified as a NaSSA (noradrenergic and specific
serotonergic antidepressant). Antagonism of alpha 2-adrenergic
receptors leads to blockade of presynaptic autoreceptors and thus
enhances norepinephrine release, while blockade of heteroreceptors on serotonergic neurons increases serotonin release. With 5HT2 and 5-HT3 receptor blockade, enhanced serotonin release
results in a net increase in 5-HT1 mediated neurotransmission (de
Boer 1995), which is considered to be related to the antidepressant
effect of mirtazapine (de Boer 1996).
Mirtazapine is usually prescribed to patients at 15 mg/day as the
starting dose and the maintenance dose is generally not more than
45 mg/day. Because of the unique pharmacology of mirtazapine,
antihistaminergic effects have been thought to predominate at
lower doses (causing drowsiness, sedation), whilst noradrenergic
neurotransmission increases with increasing doses to counteract
some of the antihistaminergic effects. Dry mouth, sedation, and
increases in appetite and body weight have been reported as the
most common adverse effects (Anttila 2001).
Why it is important to do this review
The efficacy of mirtazapine has been investigated through several
meta-analyses, especially compared with a placebo or amitriptyline. A meta-analysis of eight randomised controlled clinical trials (RCTs) showed that mirtazapine is superior to placebo and is
comparable to amitriptyline for the treatment of patients with major depression (Fawcett 1998). However, that review is outdated
because 11 years have elapsed since its publication.
Regarding a comparison with SSRIs, only limited evidence has
been established to date. A Cochrane review for fluoxetine showed
that mirtazapine was more effective than fluoxetine (Cipriani
2005). Several RCTs have examined the efficacy of mirtazapine in
comparison with other newer antidepressants, including paroxetine (Benkert 2000; Schatzberg 2002), sertraline (Behnke 2003),
citalopram (Leinonen 1999) and trazodone (van Moffaert 1995).
In those RCTs, mirtazapine was consistently reported to have a
faster onset of action than the other agents on core symptoms of
depression (Thase 2005; Thase 2006) but, to our knowledge, no
overall systematic quantitative review has been published for these
comparisons.
In addition, the profile of adverse events related to mirtazapine has
been controversial. Mirtazapine was thought to have no association with sexual side effects (Anttila 2001; Kent 2000). However, a
cross-sectional survey has shown that 41% of patients taking mirtazapine in primary care clinics experienced sexual dysfunction,
similar to paroxetine (Clayton 2002). Therefore, the comparative
efficacy and adverse effects of mirtazapine against antidepressants
other than fluoxetine remain uncertain.
A group of researchers agreed to join forces under the rubric of
the Multiple Meta-Analysis of New Generation Antidepressants
Study (MANGA study) to systematically review all available evidence for each specific, newer antidepressant. We have, to date,
completed or planned head-to-head meta-analyses for individual newer antidepressants in comparison with all the other antidepressive agents. The newer antidepressants included bupropion, citalopram (Imperadore 2007), duloxetine (Nose 2007), escitalopram (Cipriani 2009b), fluoxetine (Cipriani 2005), fluvoxamine (Omori 2010), milnacipran (Nakagawa 2009), paroxetine
(Cipriani 2007a), sertraline (Cipriani 2009), venlafaxine (Cipriani
2007b), reboxetine (Churchill 2009) and mirtazapine.
Although the overall efficacy, tolerability and information about
the adverse event profile of mirtazapine in treatment for major depression, in comparison with other antidepressants, has been pub-
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
3
lished elsewhere (Watanabe 2008; Watanabe 2010) the presented
data have been outdated.
This review aims to provide a comprehensive summary of the information about the overall efficacy, tolerability and adverse events
for mirtazapine compared with other antidepressants used in the
treatment of major depression, and will update previously published findings (Watanabe 2008; Watanabe 2010).
OBJECTIVES
1. To determine the efficacy of mirtazapine in comparison
with other antidepressive agents in acute-phase treatment for
major depression
2. To review the acceptability of mirtazapine in comparison
with that of other antidepressive agents in acute-phase treatment
for major depression
3. To investigate the adverse effects of mirtazapine in
comparison with other antidepressive agents in acute-phase
treatment for major depression
METHODS
Criteria for considering studies for this review
Types of studies
Randomised controlled trials, with individual participant or cluster randomisation, were included. Quasi-randomised trials, such
as those allocating participants by using alternate days of the week,
were excluded. For trials which had a crossover design only results
from the first randomisation period were considered.
Studies in which less than 20% of the participants suffered from
bipolar depression were included.
Exclusion criteria
A concurrent primary diagnosis of Axis I or II disorders was an
exclusion criterion. We excluded participants with the subtype:
with psychotic features. Participants with a serious concomitant
medical illness were also excluded.
Types of interventions
Experimental intervention
The experimental intervention was mirtazapine used for acutephase treatment of major depression. No restrictions on dose, frequency, intensity or duration of treatment were applied.
Comparator intervention
All other antidepressive agents in the treatment of acute depression, including:
1) conventional tricyclic ADs (TCAs)
2) SSRIs (e.g. fluoxetine, fluvoxamine, citalopram, escitalopram,
paroxetine, sertraline)
3) SNRIs (e.g. duloxetine, milnacipran, venlafaxine)
4) heterocyclic ADs (e.g. maprotiline)
5) newer antidepressants (MAOIs or newer agents such as bupropion and reboxetine) and non-conventional ADs, such as herbal
products (e.g. hypericum).
No restrictions on dose, frequency, intensity and duration were
applied.
Trials in which mirtazapine was compared to another type of psychopharmacological agent (e.g. anxiolytics, anti-convulsants, antipsychotics or mood-stabilisers) were excluded. Trials in which mirtazapine or the comparator agent was used as an augmentation
strategy were also excluded.
Types of participants
Types of outcome measures
Inclusion criteria
participants aged 18 years or older, of both sexes and with a primary diagnosis of unipolar major depression diagnosed according
to any of the standardised criteria: Feighner criteria, Research Diagnostic Criteria, DSM-III (APA 1980), DSM-III-R (APA 1987),
DSM-IV (APA 1994) or ICD-10 (WHO 1992) were included.
We included the following subtypes: chronic, with catatonic features, with melancholic features, with atypical features, postpartum onset, seasonal pattern. participants with co-morbid mental disorders that were not their primary diagnosis were included.
We decided, a priori, to subdivide the treatment outcome indices
into:
1. at two weeks after commencement of treatment;
2. after the conclusion of the acute-phase treatment (between
6 and 12 weeks);
3. after the conclusion of continuation treatment (between 4
and 6 months).
After the conclusion of the acute-phase treatment was defined as
the primary time point. For each outcome, a risk ratio (RR) of
mirtazapine in comparison with each type of antidepressant class
was examined in the primary analyses (see Data synthesis).
Mirtazapine versus other antidepressive agents for depression (Review)
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Primary outcomes
Response
The primary outcome in our systematic review was defined as a response, after the conclusion of acute-phase treatment, represented
by a reduction of at least 50% in the score on the Hamilton Rating
Scale for Depression (HAM-D) (Hamilton 1960), MontgomeryAsberg Depression Rating Scale (MADRS) (Montgomery 1979),
or ’much or very much improved’ (score 1 or 2) on the CGI-Improvement measure (Guy 1970). We did not employ the original
authors’ definitions of the primary outcomes per se because investigators or journal editors might selectively withhold some of
the measured outcomes because of the poor strength of the result (outcome reporting bias) (Furukawa 2007). Among the three
response criteria, we used the HAM-D for the primary outcome
whenever possible, even when we needed to impute response rates
(see Data synthesis) because the HAM-D has been the gold standard measure of depression severity for clinical trials of antidepressants (Williams 2001).
Secondary outcomes
Efficacy outcomes
Remission
We used remission as the secondary outcome, represented by a
score of 7 or less on the 17-item HAM-D, of 8 or less in all the other
longer versions of HAM-D, and of 11 or less on the MADRS.
Health-related quality of life (HRQoL)
The HRQoL outcomes were included in the analysis when they
were reported in a validated scale such as SF-12 or SF-36 (Ware
1993), HoNOS (Wing 1994) and WHO-QOL (WHOQOL
Group 1998).
With regard to continuous outcomes, when data were provided in
a trial both as endpoint scores and as change scores, change scores
were included in the analysis because change scores were preferable
in meta-analyses (Norman 1989; Wiebe 2003).
Tolerability and acceptability outcomes
1. Number of participants who dropped out during the trial
due to any reason.
2. Number of participants who dropped out during the trial
due to the development of adverse event.
3. Total number of participants experiencing at least some
adverse events during the trial.
4. Number of participants experiencing the following specific
individual adverse events: hypertension or tachycardia;
hypotension or bradycardia; sweating; constipation; diarrhoea;
dry mouth or decreased salivation; nausea, vomiting or gastric
distress; weight gain or increased appetite; weight loss or
anorexia; sexual dysfunction; anxiety or agitation; dizziness,
vertigo, faintness; fatigue, tiredness, asthenia; headache; tremor;
sleep disturbance; sleepiness, drowsiness, somnolence; completed
suicide, and suicide attempt.
To avoid missing any relatively rare or unexpected side effects in the
data extraction phase, we collected all adverse events data reported
in the literature and discussed ways to summarise them post hoc.
Descriptive data regarding adverse event profiles were extracted
from all available studies. Only studies reporting the number of
participants experiencing individual adverse events were retained.
Due to the variety in reporting of adverse events as presented from
the study authors’ descriptions, terms describing similar adverse
events were combined.
Search methods for identification of studies
Depression severity
Group mean scores at the end of the trial on the HAM-D, or
MADRS, or any other depression scale. We applied a looser form
of ITT analyses, whereby all the participants with at least one postbaseline measurement were represented by their last observations
carried forward.
Social adjustment
Social adjustment, social functioning including the Global Assessment of Function (Luborsky 1962) scores.
The Cochrane, Depression, Anxiety and Neurosis Review
Group’s Specialised Register (CCDANCTR)
CCDAN maintain two clinical trials registers at their editorial base
in Bristol, UK, a references register and a studies based register.
The CCDANCTR-References Register contains over 27,500 reports of trials in depression, anxiety and neurosis. Approximately
60% of these reports have been tagged to individual trials. Coded
trial records are held in the CCDANCTR-Studies Register and
records are linked between the two registers through the use of
unique Study ID tags. Reports of trials for inclusion in the Group’s
registers are collated from routine (weekly), generic searches of
MEDLINE (1950- date), EMBASE (1980 - date) and PsycINFO
(1967 - date); quarterly searches of the Cochrane Central Register
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
5
of Controlled Trials (CENTRAL) and review specific searches of
additional databases. Reports of trials are also sourced from international trials registers c/o the World Health Organisation’s trials
portal (ICTRP), drug companies, the hand-searching of key journals, conference proceedings and other (non-Cochrane) systematic reviews and meta-analyses. Details of CCDAN’s generic search
strategies used to identify RCTs can be found on the CCDAN
website.
Electronic searches
The CCDANCTR-Studies Register was searched using the following terms:
DIAGNOSIS = Depress* or Dysthymi* or “Adjustment Disorder*” or “Mood Disorder*” or “Affective Disorder” or “Affective
Symptoms”
And
INTERVENTION = Mirtazapine
The CCDANCTR-References Register was searched using freetext terms to identify any additional untagged references:
((Depress* or Dysthymi* or “Adjustment Disorder*” or “Mood
Disorder*” or “Affective Disorder” or “Affective Symptoms”) and
Mirtazapine)
Both registers were searched up to July 2011.
Searching other resources
Trial databases and trial results registers were searched for additional unpublished or ongoing studies. These included: the World
Health Organisation’s trials portal (ICTRP); ClinicalTrials.gov
and ClinicalStudyResults.org. The FDA database drugs@fda.gov
was also searched in June 2010.
Personal communication
Experts in the field were asked if they knew of any study which
met the inclusion criteria for this review. The pharmaceutical company Organon who market (and developed) Mirtazapine was also
contacted and asked to provide unpublished data (December 8,
2006).
Reference checking
The reference lists of reports of all included studies, previous systematic reviews and major textbooks of affective disorder, written
in English, were checked for published reports and citations of
unpublished research. A citation search was conducted to identify
articles citing any of the included studies.
Data collection and analysis
Selection of studies
Studies relating to mirtazapine were identified by the electronic
search of CCDANCTR-Studies and CCDANCTR-References
and other complementary searches by the Trials Search Coordinator of CCDAN. They were scanned by one author (NW) as overinconclusively as possible, firstly based on the title and abstracts.
Those studies which met the following inclusion criteria constituted the preliminary list and their full texts were retrieved.
1. Randomised trial.
2. Comparing mirtazapine against any other antidepressant.
3. participants with depression, regardless of the diagnostic
criteria used.
All the full text articles were then assessed independently by two
review authors (NW and IMO) to see if they meet the strict inclusion criteria. When the raters disagreed the final rating was made by
consensus, with the involvement of another author (TAF). Considerable care was taken to exclude duplicate publications.
Data extraction and management
Two authors (NW and IMO) independently extracted data from
the included studies concerning participant characteristics (age,
sex, depression diagnosis, comorbidity, depression severity, antidepressant treatment history for the index episode, study setting),
intervention details (intended dosage range, mean daily dosage
actually prescribed, co-intervention if any, mirtazapine as investigational drug or as comparator drug, sponsorship) and outcome
measures of interest. When any discrepancies between the data
extracted by each author occurred, the final decision was made by
consensus through discussion between the authors.
When the trial was a three (or more) armed trial that involved a
placebo arm, the data were extracted from the placebo arm as well.
Data were entered by a review author (NW) with double data
entry to avoid input errors.
Assessment of risk of bias in included studies
The methodological quality of the selected trials was assessed by using criteria based on the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2008).
Each potential risk of bias was assessed by two review authors (NW,
TAF) independently. All the judgements were made as low risk of
bias, high risk of bias or unclear risk of bias (when insufficient information provided to permit judgement) and described for each
trial in a ’Methodological quality summary’ table (Figure 1).
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Figure 1. Methodological quality summary: review authors’ judgements about each methodological quality
item for each included study.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
7
Sequence generation
The method used to generate the allocation sequence was assessed to ascertain whether the sequence was adequately generated.
Judgements were made as low risk of bias when the investigators
described a random component in the sequence generation process, such as referring to a random number table, using a computerised random number generator, coin tossing, shuffling cards or
envelopes, throwing dice, drawing of lots and minimization.
Selective outcome reporting
The completeness of outcome data was assessed to ascertain
whether the primary outcome ’response’ was adequately provided
in the original report and no imputing (see Dealing with missing
data) was required for our analysis at the primary time point, which
was the end of acute-phase treatment.
Other sources of bias
Allocation concealment
Quality of allocation concealment in the randomisation to treatment conditions was assessed to ascertain whether allocation was
adequately concealed. The judgements were made as low risk
of bias when participants and investigators enrolling participants
could not foresee assignment because one of the following, or an
equivalent method, was used to conceal allocation: central allocation (including telephone, web-based and pharmacy-controlled
randomisation); sequentially numbered drug containers of identical appearance; and sequentially numbered, opaque sealed envelopes.
Sponsorship bias was regarded as high risk of bias when the original study was funded by a pharmaceutical company or when other
sources of potential bias were detected. Other sources of bias referred to any bias in certain circumstances, for example, in relation
to trial design or setting.
Measures of treatment effect
See also Data synthesis.
Dichotomous data
Odds ratios (ORs) and their 95% confidence intervals (CIs) were
calculated.
Blinding
Quality of blinding was rated to ascertain whether the outcome
measures were assessed by an independent assessor who was blind
to treatment allocation. A self-report questionnaire can be a ’blind’
measurement if the participants were adequately blinded to their
allocated treatment. The judgements were made as low risk of bias
when any one of the following was done: no blinding, but the review authors judged that the outcome and the outcome measurement were not likely to be influenced by lack of blinding; blinding
of participants and key study personnel ensured, and unlikely that
the blinding could have been broken; either participants or some
key study personnel were not blinded but outcome assessment was
blinded and the non-blinding of others was unlikely to introduce
bias.
Continuous data
Mean differences or standardised mean differences (SMDs) and
their 95% CIs were calculated (See Data synthesis).
Unit of analysis issues
Cluster-randomised trials
The effect size in cluster-randomised trials was estimated using
the intracluster correlation coefficient (ICC), where provided, to
adjust for cluster effects.
Incomplete outcome data
Crossover trials
Adequate addressing of incomplete outcome data was regarded as
low risk of bias both when less than 20% of the allocated participants to each group were assessed and results of the assessment
were reported at the primary time point of the present review in
both intervention groups regardless of the number of participants
who dropped out from the allocated intervention, and when reasons for missing outcome data were unlikely to be related to the
true outcome.
It was planned to use the first active treatment phase in analyses.
Multi-intervention trials
For studies with two active or control arms, the results of both
comparisons were pooled by dividing the opposite arm into two
equal numbers for the purpose of avoiding unit of analysis errors
(Ramsay 2005).
Mirtazapine versus other antidepressive agents for depression (Review)
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Dealing with missing data
Dichotomous data
The analysis was calculated on an intention-to-treat (ITT) basis,
where dropouts were always included in the analysis. Where participants withdrew from the trial before the endpoint, it was assumed that they had not experienced the outcome by the end of
the trial.
When the efficacy dichotomous outcomes of interest were not
reported but baseline and endpoint means and standard deviations (SD) of the HAM-D (or any other depression scale) were
provided, we imputed the number of participants with responses
and remission by using a validated statistical method, for example according to the following formula for the response outcome
(Furukawa 2005):
number of responders at endpoint = number of participants at
endpoint * normal standard distribution corresponding to (50%
of the baseline score - endpoint score)/SD.
When the SD was not reported, its value was imputed by pooling the SDs reported in the other included trials (Altman 1996;
Furukawa 2006), although using both of these imputing methods
at the same time has not yet been empirically supported.
Data synthesis
All the analyses were conducted by NW using RevMan 5.0.
A random-effects model was used to pool the results of single
studies because we anticipated this model was likely to provide the
best fit to the data given the heterogeneity (Furukawa 2002). In
addition, the model is more conservative than a fixed-effect model
and incorporates both within-study and between-study variance.
Dichotomous data
A random-effects model using the odds ratio (OR) was used for
the primary analysis rather than a random-effects model using risk
ratio (RR) because it has been shown to have the highest generalisability in our empirical examination of summary effect measures
for meta-analyses (Furukawa 2002). The 95% confidence interval
(CI) was presented along with its precise P value. The robustness
of this summary measure was routinely examined by checking the
fixed-effect model using ORs, and the random-effects model using
RRs. Fixed-effect analyses were done routinely for the continuous
outcomes as well, to investigate the effect of the choice of method
on the estimates. Material differences between the models were
reported.
Continuous data
Continuous data
When there were missing data and the method of ’last observation
carried forward’ (LOCF) had been used to do an ITT analysis, then
the LOCF data were used with due consideration of the potential
bias and uncertainty introduced.
Only data reported with a point estimate, SDs and number of participants at the time point were included in the analysis. The above
imputation method for SDs was not used because we could not
assess the skewness of the data without SDs (See Data synthesis).
Assessment of heterogeneity
Heterogeneity between the studies was assessed by using the Chi2
test, the I2 statistic and by visual inspection of the results. A P value
of less than 0.1 for the Chi2 test or an I2 value of greater than 50%
were considered to be suggestive of heterogeneity, although these
definitions as recommended in the Cochrane Handbook might be
arbitrary because they depends on the number of studies included
in the analysis, the direction and magnitude of the treatment effects and the strength of evidence against the null hypothesis of
homogeneity. Where significant heterogeneity was detected and
was unexplained by subgroup analysis, other potential sources of
the heterogeneity were investigated.
Assessment of reporting biases
Funnel plot analysis was performed to check for existence of small
study effects including publication bias.
Continuous data were analysed using mean differences or standardised mean differences (where different measurement scales
were used) and the random-effects model. The 95% CI was presented along with its precise P value. Skewed data were presented
descriptively and were not included in the meta-analyses. Outcomes were considered skewed when the mean was smaller than
twice the SD.
P values and statistical significance
We did not set any alpha level for ’statistical significance’ in the
outcomes. Instead, the effect estimate, its 95% CI and the precise P
value were always presented because the conventional significance
threshold at P value of 0.05 is an arbitrary one, as P values are
smaller in a larger study than in a smaller study (Higgins 2008).
Subgroup analysis and investigation of heterogeneity
Subgroup analyses should be performed and interpreted with caution because multiple analyses could lead to false positive conclusions (Oxman 1992). We planned to perform the following subgroup analyses for the primary outcome.
1. For individual comparator drugs.
2. For the treatment settings (e.g. psychiatric inpatients or
outpatients in primary care), because the treatment setting is
thought to reflect the severity of depression.
3. Elderly participants (aged 65 years or older) separately from
other adult participants.
Mirtazapine versus other antidepressive agents for depression (Review)
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9
The subgroup analyses have been amended from the published
protocol, in which there are five subgroup analyses (Mirtazapine
dosing, Comparator dosing, Depression severity, Treatment settings, Elderly participants), because adequate numbers of studies
were not available for these analyses.
Where significant heterogeneity was unexplained by subgroup
analysis other potential sources, such as depression severity at baseline, focusing on refractory depression and inclusion of bipolar
participants, were investigated.
than 20%, performing the worst case/best case scenario ITT, excluding trials for which the response rates had to be calculated
based on the imputation method/borrowed from other trials, examination of “wish bias” by comparing mirtazapine as investigational drug vs mirtazapine as comparator, excluding studies funded
by the pharmaceutical company marketing mirtazapine), because
adequate numbers of studies were not available for these analyses.
RESULTS
Sensitivity analysis
Sensitivity analyses were also planned. By limiting the studies to
those with higher quality we examined if the results changed and
we meant to check for the robustness of the observed findings for
the primary outcome by:
1. excluding trials for which the response rate at the end of the
acute-phase treatment had to be calculated based on the above
imputation method;
2. excluding trials funded by or with at least one author
affiliated to a pharmaceutical company marketing mirtazapine.
This latter sensitivity analysis is particularly important in view of
the recent repeated findings that funding strongly affects outcomes
of research studies (Als-Nielsen 2003; Bhandari 2004; Lexchin
2003; Montgomery 2004; Perlis 2005; Procyshyn 2004) and because industry sponsorship and authorship of clinical trials have
been increasing over the last 20 years (Buchkowsky 2004).
The sensitivity analyses have been amended from the published
protocol, in which there are six sensitivity analyses (excluding trials with unclear concealment of random allocation and/or unclear
double blinding, excluding trials whose drop out rate is greater
Description of studies
Results of the search
Our initial search strategy yielded 94 trials including 135 references (Figure 2). After examining their titles and abstracts, 82 trials appeared to meet the inclusion criteria and their full texts were
obtained. Among these, 45 studies were written in Chinese. We
commissioned a professional translator for the full translation of
these papers. The translation process is still ongoing, so in the
present review we considered all Chinese studies as awaiting assessment. Through a contact with authors of the trials, experts in
the area and the manufacturer of mirtazapine, we also obtained information on unpublished data not yet available in the published
information (Hoyberg 1996; Schoemaker 2002; Thase 2000) and
unpublished data from the manufacturer (Organon 85146). Eight
studies were finally excluded. Twenty-nine studies with a total enrolment of 4974 participants were identified as satisfying our inclusion criteria and were included in our final analyses.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Figure 2.
Included studies
See: Characteristics of included studies.
Design
All the included trials employed randomisation for individual participants. Neither cluster nor crossover trials were identified. The
participants were followed up for six weeks (range: 2 to 24 weeks)
in a majority of the trials (15 trials). Only one trial reported data
after the end of the continuation treatment (at 24 weeks) (Wade
2003).
Participants
In all but one trial (Marttila 1995) the participants were diagnosed
to have depression based on the DSM. Elderly participants (over
65 years of age) were included in 16 trials, two trials focused
only on older adults or elderly participants. One trial limited the
participants to those aged 60 years or older (Hoyberg 1996) and
the other limited participants to those aged 65 years or older (
Schatzberg 2002). The participants with psychiatric or physical
disorders as co-morbidities with depression were excluded in a
great majority of the trials (25 trials). Female participants who
were potentially or actually pregnant or breastfeeding on entry
into the trials were also excluded in 20 trials and the other trials
did not state whether such participants were included or excluded.
Two trials focused on refractory or treatment-resistant depression
(Fava 2006; Thase 2000).
Setting
Seven trials enrolled psychiatric inpatients only (Brunnauer 2008;
Guelfi 2000; Organon 85146; Richou 1995; Schule 2006; van
Moffaert 1995; Zivkov 1995), the focus was placed on participants
in primary care in one study (Wade 2003) and both psychiatric
inpatients and outpatients were included in the other trials.
Interventions
All but four trials (Amini 2005; Benkert 2006; Schule 2006;
Winokur 2003) employed flexible dosing regimens for both the
mirtazapine and comparator arms. No trials examined different
doses or schedules of the same therapy.
Mirtazapine versus other antidepressive agents for depression (Review)
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In terms of the comparator drug, in ten trials a TCA (amitriptyline
in seven; clomipramine, doxepin and nortriptyline each in one)
was used as the comparator drug; in 13 trials an SSRI (citalopram
in one, fluoxetine in five, fluvoxamine in one, paroxetine in four
and sertraline in two) was used; in two an SNRI (venlafaxine)
was used; in two an heterocyclic AD (trazodone) was used; and in
two a newer AD (reboxetine) was used. No trials using any other
SNRIs as the comparator, such as duloxetine or milnacipran, were
identified.
A placebo pill was used as a comparator intervention in three trials
(Bremner 1995; Halikas 1995; Smith 1990).
See: Characteristics of excluded studies. Eight studies were excluded for the following reasons: not a relevant diagnostic status
(Kremer 1995; Peyron 1996; Tulen 1996), a review of other studies (Bruijin 1996; Kasper 1997a; Kasper 1997b), not employing
random allocation (Zourkova 2001), and combined therapy of
mirtazapine and another antidepressant (Blier 2004).
Ongoing studies
No ongoing studies were identified.
Studies awaiting classification
Outcomes
In all but two trials (Fava 2006; Leinonen 1999) the 17- or 21item HAM-D was used for reporting the response. With regard
to the acceptability outcomes, 23 trials provided the number of
dropouts due to any reason and 23 trials reported the number
of dropouts due to the development of adverse event during the
trials; these trial results did not always overlap.
Excluded studies
Forty-six studies written in Chinese are awaiting classification.
One study (Catterson 1996a) needs further data for checking if the
study meets the strict eligibility criteria. Seven studies (Blier 2009;
Fang 2010; Kang 2009; Kim 2011; Paslakis 2010; Sarginson 2010;
Scharnholz 2010) identified after the completion of the review are
classified in this category.
Risk of bias in included studies
Two of the three review authors (NW, IMO, TAF) independently
assessed study quality. Any discrepancy between two authors was
dissolved upon discussion (see: Figure 1; Figure 3).
Figure 3. Methodological quality graph: review authors’ judgements about each methodological quality
item presented as percentages across all included studies.
Sequence generation
None of the trials described the sequence generation process.
Allocation
None of the trials reported whether allocation concealment was
adequately performed.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Blinding
No other potential sources of bias were identified.
All trials but one (Fava 2006) were undertaken on a double-blind
basis, but none of the trials reported information to judge whether
it was likely or unlikely that the blinding had been broken.
Effects of interventions
Incomplete outcome data
Only three trials (Amini 2005; Bremner 1995; Leinonen 1999)
were rated as adequate in terms of addressing incomplete outcome
data.
ORs for the efficacy data that were larger than one (falling to the
right of the midline in a graph) and those for the acceptability and
tolerability data that were smaller than one indicate a difference
in favour of mirtazapine.
1. Mirtazapine versus tricyclic antidepressants (TCAs)
Selective reporting
Outcomes in terms of the primary outcome (response) at the primary time point (at the end of acute-phase treatment) were obtained in all but two trials (Hoyberg 1996; Winokur 2003) without using the imputation method.
Other potential sources of bias
One study (Fava 2006) was funded by the National Institute of
Mental Health (NIMH), and one study (Amini 2005) was unclear
in terms of sponsorship bias. The other studies were sponsored by,
or had at least one author affiliated to, a pharmaceutical company.
Primary analysis
1.1 Primary outcome: response
There was no robust evidence to detect a difference between mirtazapine and TCAs in terms of the response outcome at two weeks
(8 studies; OR 0.85, 95% CI 0.64 to 1.13, P = 0.27) (Analysis
1.1; Figure 4) and at end of the acute-phase treatment (9 studies;
OR 0.89, 95% CI 0.72 to 1.10, P = 0.29) (Analysis 1.2; Figure
5). No substantial heterogeneity was observed.
Mirtazapine versus other antidepressive agents for depression (Review)
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Figure 4. Forest plot of comparison: 1 MIRTAZAPINE vs TCAs, outcome: 1.1 Primary outcome (response)
at 2 weeks.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Figure 5. Forest plot of comparison: 1 MIRTAZAPINE vs TCAs, outcome: 1.2 Primary outcome (response)
at end of the acute-phase treatment.
1.2 Secondary outcomes
There was robust evidence to detect any difference between mirtazapine and TCAs in terms of the remission outcome at two weeks
(8 studies; OR 0.85, 95% CI 0.55 to 1.32, P = 0.47) (Analysis
1.3) and at end of the acute-phase treatment (9 studies; OR 0.86,
95% CI 0.69 to 1.08, P = 0.19) (Analysis 1.4).
Two studies (Mullin 1996; Zivkov 1995) contributed to the metaanalysis at two weeks and one study (Organon 85146) did so
at the end of acute-phase treatment. Information from studies
with skewed data were not included in the meta-analysis but were
included in a descriptive table (Analysis 1.32; Analysis 1.33). From
the results of the meta-analysis, there was no robust evidence to
detect a difference between mirtazapine and TCAs in terms of
depression severity on a continuous scale at two weeks (2 studies;
Analysis 1.5) and at the end of the acute-phase treatment (1 study;
Analysis 1.6).
1.2.2 Depression severity
1.2.3 Social adjustment
1.2.1 Remission
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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One study (Mullin 1996) contributed to the meta-analysis at two
weeks and three studies (Marttila 1995; Mullin 1996; Richou
1995) did so at the end of the acute-phase treatment. There was
no robust evidence to detect a difference between mirtazapine and
TCAs in terms of social adjustment at two weeks (1 study; Analysis
1.7) and at end of the acute-phase treatment (3 studies; Analysis
1.8).
1.3.1 Individual comparator drugs
There was no robust evidence to detect a difference between mirtazapine and any specific type of TCA comparator in terms of the
response outcome during the acute-phase treatment (8 studies at
2 weeks: Analysis 1.1, 9 studies at end of acute-phase treatment:
Analysis 1.2).
1.3.2 Treatment settings
1.2.4 Health-related quality of life (HRQoL)
No data were available.
1.2.5 Withdrawal due to any reason
No studies focused on participants in primary care clinics only.
Limiting findings to studies focusing on psychiatric inpatients,
there was no robust evidence to detect a difference between mirtazapine and TCAs in terms of the response to acute-phase treatment (2 studies at 2 weeks: Analysis 1.28, 3 studies at end of the
acute-phase treatment: Analysis 1.29).
There was no robust evidence to detect a difference between mirtazapine and TCAs in terms of withdrawal due to any reason during the acute-phase treatment (7 studies; Analysis 1.9).
1.3.3 Elderly participants
No studies focused on elderly participants only.
1.2.6 Withdrawal due to the development of an adverse event
There was no robust evidence to detect a difference between mirtazapine and TCAs in terms of withdrawal due to the development
of an adverse event during the acute-phase treatment (8 studies;
Analysis 1.10).
1.4 Sensitivity analysis
1.4.1 Studies without imputation
1.2.7 Having some adverse events
There was no robust evidence to detect a difference between mirtazapine and TCAs in terms of developing adverse events during
the acute-phase treatment (2 studies; Analysis 1.11).
All but one study (Hoyberg 1996) did not need any imputation
method for the primary outcome at the end of the acute-phase
treatment. Limiting findings to these studies, there was no robust
evidence to detect a difference between mirtazapine and TCAs
in terms of the response to acute-phase treatment (7 studies at 2
weeks: Analysis 1.30, 8 studies at end of the acute-phase treatment:
Analysis 1.31).
1.2.8 Individual adverse events
No data were available with regard to diarrhoea, weight loss and
completed suicide. Mirtazapine was less likely than TCAs to bring
on hypertension or tachycardia (4 studies; OR 0.44, 95% CI 0.24
to 0.81, P = 0.008) (Analysis 1.12) and tremor (7 studies; OR
0.36, 95% CI 0.22 to 0.57, P < 0.0001) (Analysis 1.24). There
was no robust evidence to detect a difference between mirtazapine
and TCAs in terms of developing other types of individual adverse
events.
1.4.2 Studies without sponsorship bias
Secondary analysis
Primary analysis
1.3 Subgroup analysis and investigation of heterogeneity
2.1 Primary outcome: response
From one study (Fava 2006), there was no robust evidence to
detect a difference between mirtazapine and TCAs in the response
to acute-phase treatment.
2. Mirtazapine versus selective serotonin reuptake
inhibitors (SSRIs)
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
16
In comparison with SSRIs, mirtazapine was shown to be significantly more effective in terms of response at two weeks (12 studies;
OR 1.57, 95% CI 1.30 to 1.88, P < 0.00001) (Analysis 2.1; Figure
6) and at the end of acute-phase treatment (12 studies; OR 1.19,
95% CI 1.01 to 1.39, P = 0.04) (Analysis 2.2; Figure 7). There
was no robust evidence to detect a difference between mirtazapine
and SSRIs at the end of the continuation treatment (at 24 weeks)
based on one study (Wade 2003) (1 study; OR 1.60, 95% CI 0.91
to 2.81, P = 0.10) (Analysis 2.3). No substantial heterogeneity was
observed at any of the three time points.
Mirtazapine versus other antidepressive agents for depression (Review)
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Figure 6. Forest plot of comparison: 2 MIRTAZAPINE vs SSRIs, outcome: 2.1 Primary outcome (response)
at 2 weeks.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Figure 7. Forest plot of comparison: 2 MIRTAZAPINE vs SSRIs, outcome: 2.2 Primary outcome (response)
at end of the acute-phase treatment.
2.2 Secondary outcomes
2.2.1 Remission
Mirtazapine was shown to be significantly more effective than
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
19
SSRIs in terms of the remission outcome at two weeks (12 studies;
OR 1.82, 95% CI 1.36 to 2.44, P < 0.0001) (Analysis 2.4). At the
end of the acute-phase treatment, there was no robust evidence
to detect a difference between mirtazapine and SSRIs (12 studies;
OR 1.17, 95% CI 0.98 to 1.40, P = 0.08) (Analysis 2.5). There
was no robust evidence to detect a difference between mirtazapine
and SSRIs at the end of the continuation treatment (1 study; OR
1.89, 95% CI 1.01 to 3.54, P = 0.05) (Analysis 2.6).
2.2.2 Depression severity
No data were available for the meta-analysis. Information from
studies with skewed data were not included in the meta-analysis
but in a descriptive table (2 studies at 2 weeks: Analysis 2.31, 3
studies at end of the acute-phase treatment: Analysis 2.32).
2.2.3 Social adjustment
2.2.8 Individual adverse events
No data were available with regard to hypertension or tachycardia
and completed suicide. In comparison with SSRIs, mirtazapine
was more likely to cause dry mouth (10 studies; OR 1.80, 95% CI
1.37 to 2.36, P < 0.0001) (Analysis 2.14), weight gain or increased
appetite (11 studies; OR 4.23, 95% CI 2.93 to 6.11, P < 0.00001)
(Analysis 2.16), fatigue (8 studies; OR 1.53, 95% CI 1.08 to 2.15,
P = 0.02) (Analysis 2.21) and somnolence (11 studies; OR 1.81,
95% CI 1.39 to 2.37, P < 0.0001) (Analysis 2.25) but less likely
to cause sweating (5 studies; OR 0.25, 95% CI 0.15 to 0.44, P <
0.00001) (Analysis 2.11), diarrhoea (8 studies; OR 0.57, 95% CI
0.41 to 0.80, P = 0.001) (Analysis 2.13), nausea or vomiting (11
studies; OR 0.33, 95% CI 0.26 to 0.43, P < 0.00001) (Analysis
2.15), sexual dysfunction (4 studies; OR 0.31, 95% CI 0.13 to
0.74, P = 0.009) (Analysis 2.18), headache (11 studies; OR 0.69,
95% CI 0.56 to 0.86, P = 0.0008) (Analysis 2.22), tremor (5
studies; OR 0.34, 95% CI 0.18 to 0.66, P = 0.001) (Analysis 2.23)
or sleep disturbance (5 studies; OR 0.52, 95% CI 0.31 to 0.86, P
= 0.01) (Analysis 2.24). There was no robust evidence to detect a
difference between mirtazapine and SSRIs in terms of developing
other types of individual adverse events.
No data were available.
Secondary analysis
2.2.4 Health-related quality of life (HRQoL)
2.3 Subgroup analysis and investigation of heterogeneity
No data were available.
2.3.1 Individual comparator drugs
2.2.5 Withdrawal due to any reason
There was no robust evidence to detect a difference between mirtazapine and SSRIs in terms of withdrawal due to any reason during the acute-phase treatment (11 studies; Analysis 2.7).
2.2.6 Withdrawal due to the development of an adverse event
In terms of response at two weeks, mirtazapine was shown to be
significantly more effective than paroxetine (3 studies; OR 2.39,
95% CI 1.42 to 4.02, P = 0.001) and sertraline (2 studies; OR
1.45, 95% CI 1.04 to 2.02, P = 0.03) (Analysis 2.1). Mirtazapine
was shown to be significantly more effective than fluoxetine at
the end of the acute-phase treatment (5 studies; OR 1.55, 95%
CI 1.07 to 2.23, P = 0.02) (Analysis 2.2). There was no robust
evidence to detect a difference between mirtazapine and the other
individual comparator drugs.
There was no robust evidence to detect a difference between mirtazapine and SSRIs in terms of withdrawal due to the development
of an adverse event during the acute-phase treatment (11 studies;
Analysis 2.8).
2.3.2 Treatment settings
2.2.7 Having some adverse events
2.3.3 Elderly participants
There was no robust evidence to detect a difference between mirtazapine and SSRIs in terms of developing any adverse events during the acute-phase treatment (7 studies; Analysis 2.9).
Based on one study (Schatzberg 2002), mirtazapine was shown to
be significantly more effective than paroxetine at two weeks (OR
2.59, 95% CI 1.35 to 4.97, P = 0.004) (Analysis 2.1). There was
No studies focused on psychiatric inpatients or participants in
primary care clinics only.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
20
no robust evidence to detect a difference between mirtazapine and
paroxetine at the end of the acute-phase treatment (OR 1.41, 95%
CI 0.86 to 2.32, P = 0.17) (Analysis 2.2).
3.2.2 Depression severity
2.4 Sensitivity analysis
3.2.3 Social adjustment
No data were available for the meta-analysis.
No data were available.
2.4.1 Studies without imputation
All but one study (Winokur 2003) did not need any imputation method for the primary outcome at the end of the acutephase treatment. Limiting findings to these studies, mirtazapine
was shown to be significantly more effective than SSRIs in terms
of response at two weeks (11 studies; OR 1.58, 95% CI 1.31 to
1.90, P < 0.00001) (Analysis 2.29). There was no robust evidence
to detect a difference between mirtazapine and SSRIs at the end
of the acute-phase treatment (11 studies; OR 1.17, 95% CI 1.00
to 1.38, P = 0.05) (Analysis 2.30).
3.2.4 Health-related quality of life (HRQoL)
No data were available.
3.2.5 Withdrawal due to any reason
Mirtazapine was shown to be significantly more effective than
venlafaxine in terms of withdrawal due to any reason (2 studies;
OR 0.65, 95% CI 0.43 to 0.99, P = 0.04) during the acute-phase
treatment (Analysis 3.5).
2.4.2 Studies without sponsorship bias
All studies were funded by a pharmaceutical company.
3. Mirtazapine versus serotonin-noradrenaline
reuptake inhibitors (SNRIs)
3.2.6 Withdrawal due to the development of adverse event
There was no robust evidence to detect a difference between mirtazapine and venlafaxine in terms of withdrawal due to the development of adverse event during the acute-phase treatment (2
studies; Analysis 3.6).
Primary analysis
3.2.7 Having some adverse events
3.1 Primary outcome: response
Mirtazapine was shown to be significantly more effective than
venlafaxine at two weeks (2 studies; OR 2.29, 95% CI 1.45 to
3.59, P = 0.0003) (Analysis 3.1) and at the end of the acute-phase
treatment (2 studies; OR 1.53, 95% CI 1.03 to 2.25, P = 0.03)
(Analysis 3.2). No substantial heterogeneity was observed.
3.2 Secondary outcomes
3.2.1 Remission
Mirtazapine was shown to be significantly more effective than venlafaxine in terms of the remission outcome at two weeks (2 studies;
OR 2.34, 95% CI 1.07 to 5.13, P = 0.03) (Analysis 3.3). At the
end of the acute-phase treatment, there was no robust evidence to
detect a difference between mirtazapine and venlafaxine (2 studies; OR 1.55, 95% CI 0.98 to 2.47, P = 0.06) (Analysis 3.4).
There was no robust evidence to detect a difference between mirtazapine and venlafaxine in terms of developing any adverse events
during the acute-phase treatment (1 study; Analysis 3.7).
3.2.8 Individual adverse events
No data were available with regard to hypertension or tachycardia, diarrhoea, weight gain or increased appetite, weight loss or
anorexia, sexual dysfunction, dizziness or vertigo, tremor and attempted suicide. In comparison with venlafaxine, mirtazapine was
more likely to cause fatigue (1 study; OR 2.43, 95% CI 1.30 to
4.55, P = 0.006) (Analysis 3.14) but less likely to cause sweating
(1 study; OR 0.03, 95% CI 0.00 to 0.45, P = 0.01) (Analysis 3.9),
constipation (1 study; OR 0.22, 95% CI 0.06 to 0.83, P = 0.02)
(Analysis 3.10) or sleep disturbance (1 study; OR 0.02, 95% CI
0.00 to 0.41, P = 0.01) (Analysis 3.16). There was no robust evidence to detect a difference between mirtazapine and venlafaxine
in terms of developing other types of individual adverse events.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
21
Secondary analysis
(Analysis 4.1) or at the end of the acute-phase treatment (2 studies; OR 1.50, 95% CI 0.95 to 2.37, P = 0.08) (Analysis 4.2). No
substantial heterogeneity was observed.
3.3 Subgroup analysis and investigation of heterogeneity
4.2 Secondary outcomes
3.3.1 Individual comparator drugs
No studies focusing on SNRIs other than venlafaxine were identified.
3.3.2 Treatment settings
No studies focused on participants in primary care clinics only. In
terms of inpatients, based on one study (Guelfi 2000) no robust
evidence was observed to detect a difference between mirtazapine
and venlafaxine at two weeks (OR 1.88, 95% CI 0.97 to 3.64, P
= 0.06) (Analysis 3.1) or at the end of the acute-phase treatment
(OR 1.64, 95% CI 0.87 to 3.10, P = 0.13) (Analysis 3.2).
4.2.1 Remission
There was no robust evidence to detect a difference between mirtazapine and trazodone at two weeks (2 studies; OR 1.00, 95%
CI 0.36 to 2.80, P = 1.00) (Analysis 4.3) and at the end of the
acute-phase treatment (2 studies; OR 1.38, 95% CI 0.76 to 2.52,
P = 0.29) (Analysis 4.4).
4.2.2 Depression severity
No data were available for the meta-analysis.
3.3.3 Elderly participants
No studies focused on elderly participants only.
4.2.3 Social adjustment
No data were available.
3.4 Sensitivity analysis
4.2.4 Health-related quality of life (HRQoL)
3.4.1 Studies without imputation
The two studies did not need any imputation method for the
primary outcome at the end of the acute-phase treatment and the
results of the analysis were the same as those from the primary
analyses (Analysis 3.1; Analysis 3.2).
3.4.2 Studies without sponsorship bias
No data were available.
4.2.5 Withdrawal due to any reason
There was no robust evidence to detect a difference between mirtazapine and trazodone in terms of withdrawal due to any reason
during the acute-phase treatment (2 studies; OR 0.90, 95% CI
0.47 to 1.72, P = 0.76) (Analysis 4.5).
All studies were funded by a pharmaceutical company.
4. Mirtazapine versus heterocyclic antidepressants
Primary analysis
4.2.6 Withdrawal due to the development of an adverse event
There was no robust evidence to detect a difference between mirtazapine and trazodone in terms of withdrawal due to the development of an adverse event during the acute-phase treatment (2
studies; OR 0.61, 95% CI 0.25 to 1.51, P = 0.29) (Analysis 4.6).
4.1 Primary outcome: response
There was no robust evidence to detect a difference between mirtazapine and an heterocyclic antidepressant (trazodone only) at
two weeks (2 studies; OR 1.14, 95% CI 0.64 to 2.04, P = 0.66)
4.2.7 Having some adverse events
No data were available.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
22
4.2.8 Individual adverse events
No data were available with regard to sweating, diarrhoea, nausea,
anxiety or agitation, fatigue, tremor and somnolence. In comparison with trazodone, mirtazapine was less likely to cause hypotension or bradycardia (OR 0.17, 95% CI 0.03 to 1.00, P = 0.05)
(Analysis 4.8). There was no robust evidence to detect a difference
between mirtazapine and trazodone in terms of developing other
types of individual adverse events.
Secondary analysis
4.3 Subgroup analysis and investigation of heterogeneity
5. Mirtazapine versus newer antidepressants
Primary analysis
5.1 Primary outcome: response
There was no robust evidence to detect a difference between mirtazapine and a newer antidepressant (reboxetine only) in terms of
the response outcome at two weeks (1 study; OR 1.00, 95% CI
0.18 to 5.67, P = 1.00) (Analysis 5.1) and at end of the acutephase treatment (1 study; OR 1.00, 95% CI 0.27 to 3.67, P =
1.00) (Analysis 5.2).
5.2 Secondary outcomes
4.3.1 Individual comparator drugs
No studies focusing on antidepressants other than trazodone were
identified.
4.3.2 Treatment settings
No studies focused on participants in primary care clinics only.
In terms of inpatients, based on one study (van Moffaert 1995)
no robust evidence was identified to detect a difference between
mirtazapine and trazodone in terms of the response at two weeks
(OR 1.16, 95% CI 0.54 to 2.48, P = 0.70) (Analysis 4.1) or at
the end of the acute-phase treatment (OR 1.50, 95% CI 0.86 to
2.63, P = 0.16) (Analysis 4.2).
4.3.3 Elderly participants
No studies focused on elderly participants only.
5.2.1 Remission
There was no robust evidence to detect a difference between mirtazapine and reboxetine in terms of the remission outcome at
two weeks (1 study; OR 1.00, 95% CI 0.06 to 17.18, P = 1.00)
(Analysis 5.3) and at the end of the acute-phase treatment (1 study;
OR 1.26, 95% CI 0.33 to 4.73, P = 0.74) (Analysis 5.4).
5.2.2 Depression severity
There was no robust evidence to detect a difference between mirtazapine and reboxetine in terms of the severity of depression at
two weeks (1 study; SMD -0.37, 95% CI -1.00 to 0.25, P = 0.24)
(Analysis 5.5). At the end of the acute-phase treatment the data
were skewed and presented in a descriptive table (1 study; Analysis
5.8).
4.4 Sensitivity analysis
5.2.3 Social adjustment
No data were available.
4.4.1 Studies without imputation
The two studies did not need any imputation method for the
primary outcome at the end of the acute-phase treatment and the
results of the analysis were the same as those from the primary
analysis (Analysis 4.1; Analysis 4.2).
5.2.4 Health-related quality of life (HRQoL)
No data were available.
5.2.5 Withdrawal due to any reason
4.4.2 Studies without sponsorship bias
All studies were funded by a pharmaceutical company.
Not estimable because no participant in either group withdrew
due to any reason (2 studies; Analysis 5.6).
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
23
5.2.6 Withdrawal due to the development of an adverse event
5.3.2 Treatment settings
Not estimable, because no participant in either group withdrew
due to the development of an adverse event (2 studies; Analysis
5.7).
The two studies focused on inpatients.
5.3.3 Elderly participants
No studies focused on elderly participants only.
5.2.7 Having some adverse events
No data were available.
5.4 Sensitivity analysis
5.2.8 Individual adverse events
5.4.1 Studies without imputation
No data were available with regard to any individual adverse event.
One study needed the imputation method for the primary outcome at two weeks. The other provided no usable data for the
primary outcome.
Secondary analysis
5.4.2 Studies without sponsorship bias
5.3 Subgroup analysis and investigation of heterogeneity
The two studies were funded by a pharmaceutical company.
6. Funnel plot analysis
5.3.1 Individual comparator drugs
No studies focusing on antidepressants other than reboxetine were
identified.
There was no robust evidence of publication bias or other small
study effects based on visual inspections of the funnel plot with
regard to the primary outcome (response) at the primary time
point (at the end of the acute-phase treatment) (Figure 8).
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
24
Figure 8. Funnel plot of comparison: 6 Funnel plot analysis: Primary outcome (response) at end of the
acute-phase treatment, outcome: 6.1 vs all compounds.
DISCUSSION
Summary of main results
This systematic review and meta-analysis examined the efficacy,
acceptability and tolerability of mirtazapine for the acute-phase
treatment for depression, in comparison with other antidepressive
agents.
In terms of the primary outcome, overall a response was achieved
at two weeks in 616 (26.6%) of the 2316 participants treated
with mirtazapine, and in 1413 (61.0%) out of the 2316 participants treated with mirtazapine at the end of the acute-phase treatment. In terms of one of the secondary outcomes, a remission
was achieved in 222 (9.6%) of the 2316 participants treated with
mirtazapine at two weeks, and in 847 (36.6%) out of the 2316
participants treated with mirtazapine at the end of acute-phase
treatment. In terms of acceptability, 512 (25.2%) out of the 2030
participants treated with mirtazapine withdrew from treatment at
some time point during the course of treatment.
We concluded from the results that there was no robust evidence
to detect a difference between mirtazapine and other types of antidepressants in terms of the response outcome at the end of the
acute-phase treatment, at approximately six weeks. At two weeks,
mirtazapine is likely to be more effective than either SSRIs or
SNRIs, especially paroxetine and venlafaxine. These results were
confirmed even after an additional sensitivity analysis was conducted that excluded the two trials (Fava 2006; Thase 2000) that
focused on treatment-resistant depression. In terms of tolerability,
mirtazapine was not statistically significantly superior or inferior
to other antidepressants.
Due to the unique pharmacological profile of mirtazapine, some
anti-histaminergic effects have been thought to bring about
drowsiness, sedation, dry mouth and an increase in appetite and
body weight (Kent 2000). These side effects might result in a
dropout of participants treated with mirtazapine. Approximately
70% of the participants treated with mirtazapine experienced at
least one adverse event during the trials; and dry mouth, somnolence, weight or appetite increase, fatigue and headache were the
most frequently observed. In comparison with SSRIs, treatment
with mirtazapine was significantly more likely to lead to the development of dry mouth, weight gain or increased appetite, fa-
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
25
tigue and somnolence but was significantly less likely to lead to the
development of sweating, diarrhoea, nausea or vomiting, sexual
dysfunction, headache, tremor and sleep disturbance.
Overall completeness and applicability of
evidence
Participants
All but two studies (Fava 2006; Thase 2000) included in this
review were not conducted for refractory depression. Psychiatric
inpatients were included in five studies (Guelfi 2000; Organon
85146; Richou 1995; van Moffaert 1995; Zivkov 1995), participants in primary care were included in one study (Wade 2003)
and the other 19 studies included both psychiatric inpatients and
outpatients. The findings from this review, therefore, may not be
representative of participants with refractory depression nor mildly
affected participants frequently seen in primary care. Moreover,
there was only one trial in which recruitment was wholly conducted for the depressive elderly (Schatzberg 2002. The findings
from this review may therefore not be representative for the depressive elderly.
Interventions
Considering the often chronic and recurrence-prone presentation
of major depression, long-term or follow-up interventions are often required for optimal treatment of this disorder. However, we
could find only one study (Wade 2003) examining the long-term
efficacy of mirtazapine for major depression.
Outcomes
Treatments for major depression should be assessed not only by
psychiatric symptoms but also by general functioning and quality
of life. However, no trials included in this review incorporated
those outcomes. Considering that major depression is associated
with a marked personal, social and economic morbidity, the underinvestigation of these outcomes is a problem.
Quality of the evidence
No trials described methods of random sequence generation, and
no trials reported the method of allocation concealment. It is conceivable that selection bias might have occurred in the trials included in this review. These methodologies should be adequately
reported, as recommended in the CONSORT 2010 statement
(Schulz 2010).
Physician and participant blinding were sought in all but one study
(Fava 2006). However, no test of blinding success was conducted in
any study. As a whole, there was little information on the outcome
assessment process and the extent to which detection bias might
have occurred was uncertain.
At the end of the acute-phase treatment, only four studies (Amini
2005; Bremner 1995; Brunnauer 2008; Leinonen 1999) reported
the outcomes for an 80% or higher proportion of participants
initially allocated to treatment conditions, and the other studies
probably did not due to higher dropout rates. This high attrition
rate could have influenced treatment outcomes.
All but two trials (Amini 2005; Fava 2006) included in our metaanalysis were funded or conducted under the advice of a manufacturer of mirtazapine. On the other hand, it has been repeatedly reported that industry sponsorship could influence trial outcomes in
favour of a drug manufacturer (Als-Nielsen 2003; Lexchin 2003;
Perlis 2005). The present review may suffer from sponsorship bias.
Potential biases in the review process
Some possible strengths and limitations of this review should be
noted.
Strengths
First, we imputed the response and remission outcomes by applying the threshold of the most conventional and prevalent depression severity scales using a validated statistical method; we did
not use the outcomes defined by the authors of the original trials. Although this methodology may appear arbitrary and to have
possibly resulted in the loss of important information from the
original trials, recent evidence has shown that in published RCTs
the statistically significant outcomes for efficacy tend to be more
fully reported than non-significant outcomes do, and that in 62%
of trials at least one primary outcome was changed, introduced or
omitted with reference to the protocols (Chan 2004; Furukawa
2007). For this reason, we decided to adhere to our criteria defined
a priori for the response and remission outcomes and impute them
if they were not unavailable from the original trials. We think that,
as long as the selective reporting of outcomes remains prevalent,
our methodology should be used in future systematic reviews.
Second, in addition to the response rate we took the remission rate
into account as one of the outcomes. Previously reported metaanalyses have generally taken only the response outcome into account. However, a recent series of RCTs on the effectiveness of the
sequential use of antidepressants and cognitive-behavioural therapy for depression, named STAR*D and one of which (Fava 2006)
was included in our systematic review, revealed that the remission
rate was more consistently associated with a better prognosis in
terms of the long-term outcome than the response (Rush 2007).
We, therefore, propose that all future studies on this subject should
report on the remission outcome in addition to the response outcome for depression.
Limitations
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
26
First of all, industry sponsorship can influence trial outcomes in
favour of a drug manufacturer. We were unable to rule out the
possibility that the dosing of either mirtazapine or the comparator
drug might have been designed in such a way as to induce differences in favour of mirtazapine because the doses of the comparator drugs seemed lower than the usual doses in clinical practice in
some of the included trials, especially in some of the trials comparing mirtazapine with fluoxetine or paroxetine (see: Characteristics
of included studies). We initially intended to conduct a sensitivity
analysis by excluding trials sponsored by pharmaceutical companies, but did not because only two out of the 25 trials were free of
industry sponsorship.
The second limitation of the review was the treatment durations in
the included RCTs (see also: Quality of the evidence). Sixteen out
of the 25 included trials followed up the participants for only six
weeks. The STAR*D study revealed that one third of those showing a response to treatment with antidepressants did so only after
six weeks of therapy (and half of those who showed remission did
so after six weeks) (Rush 2007). In addition, the durations of the
RCTs included in our analysis were not sufficiently long to address
the long-term side effects of mirtazapine. Long-term side effects
should be considered as much as those observed in the short term
because they could play a big part in determining the burden and
effective outcome of therapies (Hoyberg 1996; Trivedi 2006); and
rare but otherwise crucial outcomes could occur only in the long
term. Furthermore, some adverse events including nausea tend to
subside rapidly (Mullin 1996), whereas other adverse events including weight gain might be an ongoing problem that has potentially serious health implications in the long term. Future studies
should include long-term adverse events among their outcomes.
Addressing them may require a systematic review of studies dealing with the long-term effects of the drug in study designs other
than RCTs; this review focused only on RCTs.
We are also concerned about the representativeness of the populations recruited in the included trials. Most of the included trials
were carried out to investigate the efficacy of mirtazapine. Generally speaking, efficacy trials tend to include only symptomatic
volunteers with no concomitant medical or psychiatric disease as
opposed to enrolling participants seeking health care in typical
clinical treatment settings (Trivedi 2006). Thus, efficacy trials may
eventually lead to results with only limited ecological validity and
generalisability to clinical practice. Future research on mirtazapine should include effectiveness trials enrolling participants seen
in everyday practice.
Lastly, only one author was involved in the first stage of selecting
studies and in making the preliminary list of potentially eligible
studies, due to shortage of initial human resources in the review
procedure. This might have led to possible human error in selection. However, selecting studies in this stage was conducted as
over-inclusively as possible, and all the full text articles in this preliminary list were assessed by two review authors independently
(NW and IMO). The final rating were made by consensus.
Agreements and disagreements with other
studies or reviews
There have been several other reviews published recently that investigate the efficacy of mirtazapine in comparison with other types
of antidepressants.
Although the faster onset of therapeutic action of mirtazapine in
comparison with that of the SSRIs has been reported previously
from a non head-to-head review of the results from three RCTs
(Quitkin 2001), our systematic review showed that this result on
comparative efficacy was not the same for all SSRIs.
The most recent review compared the remission rates and time to
remission in participants with major depression taking either mirtazapine or an SSRI through a meta-analysis of the individual participant data from 15 RCTs (Thase 2010). This review concluded
that mirtazapine therapy resulted in significantly higher remission
rates than SSRI therapy during six weeks of treatment, particularly within the first 15 days of treatment. Another recently published review compared the benefits and harms of 12 second-generation antidepressants for the treatment of depression in adults
(Gartlehner 2008). It concluded that the clinical response and
remission rates are similar among second-generation antidepressants, including mirtazapine, at the end of the acute-phase treatment. In terms of onset of action, this review concluded that mirtazapine has a significantly faster onset of action than citalopram,
fluoxetine, paroxetine or sertraline.
The results from these reviews appear to be quite similar to those
from the present review, although we have to be cautious to draw a
definitive conclusion given the possibility of sponsorship bias and
the width of confidence intervals of the outcomes.
We have recently published a multiple-treatments meta-analysis
(MTM) in which our data for mirtazapine were merged with
those for 11 other new generation antidepressants and both the
direct and indirect comparisons were statistically pooled (Cipriani
2009a). The MTM offers a clinically meaningful synthesis when
several competing treatments are available for one disease (Lu
2006; Lumley 2002; Salanti 2008), as is the case with major depression, while examining the overall strength and consistency of
the network of evidence. In this MTM, mirtazapine emerged as
one of the top four antidepressants in terms of response but not
in terms of acceptability. The relative merits and drawbacks of direct versus MTM comparisons are still debatable (Bucher 1997;
Ioannidis 2006; Song 2003) and we need to carefully weigh up
and synthesise the direct with indirect comparisons.
AUTHORS’ CONCLUSIONS
Implications for practice
Although mirtazapine is more likely to have a better efficacy profile
than paroxetine or venlafaxine in terms of response at two weeks, in
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
27
view of the similar efficacy of mirtazapine and other antidepressant
agents at the end of the acute-phase treatment (at approximately
six weeks), and of possible sponsorship bias, the results of the
study led us to conclude that clinicians should also focus on other
practically or clinically relevant considerations, such as differences
in the side-effect profiles, to tailor the treatment to best fit an
individual participant’s needs.
should be funded by non-profit organizations. Furthermore, future trials should include appropriate QoL outcome measures and
should adequately report the method of generation of random sequence, allocation concealment, and blinding in accordance with
the CONSORT 2010 statement. Finally, the effectiveness of mirtazapine should be investigated by conducting RCTs recruiting
participants from populations seeking treatment in ordinary clinical practice settings.
Mirtazapine is less likely to cause tremor than TCAs, and nausea
and sexual dysfunction than SSRIs, but is more likely to cause
weight gain and somnolence.
ACKNOWLEDGEMENTS
Implications for research
Since the great majority of trials on the efficacy of mirtazapine are
funded by the manufacturer, and thus might be subject to some
sponsorship bias, future RCTs on the effectiveness of mirtazapine
The authors would like to thank Julian Higgins, Georgia Salanti
and John Geddes for their helpful comments and feedback on
the protocol. We would also like to thank Hugh McGuire for his
assistance with this review.
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Zourkova 2001 {published data only}
∗
Zourkova A. Effect of mirtazapine and paroxetine on
residual symptoms of depressive disorders and their effect
on P450 CYP 2D6 activity. Homeostasis in Health and
Disease 2001;41(6):242–9.
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Blier 2009 {published data only}
Blier P, Gobbi G, Turcotte JE, de Montigny C, Boucher
N, Hebert C, et al. Mirtazapine and paroxetine in
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their combination from treatment initiation. European
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Catterson 1996a {unpublished data only}
Catterson ML, Preskorn SH. Double-blind crossover study
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Chang 2006 {published data only}
Chang FW, Ma YP, Yan F, Wang CH. Comparative study
of mirtazapine vs clomipramine in treatment of dysthymic
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Chen X, Tan L, Zhao J, Li L, Chen Y. Randomized
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Gong 2005 {published data only}
Gong C, Xu H, Xiang D, Zhou X. Comparative study on
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Guo 2005 {published data only}
Guo HR, Ren YM, Li SY. Controlled study of mirtazapine
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Guo 2005a {published data only}
Guo P, Guo H, Jia J. Comparison of mirtazapine versus
clomipramine in maintenance treatment of depression.
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Guo 2006 {published data only}
Guo P. Clinical evaluation of mirtazapine and clomipramine
for the treatment of depressive disorder associated with
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Guo 2006a {published data only}
Guo JH, Cao CA, Liao CP. Effect of Mirtazapine and
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Hang R, Xu P, Wang R. A comparative study of mirtazapine
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Hu 2004 {published data only}
Hu S, Xu Y, Wei N, et al. A comparative study of treatment
of depression: Mirtazapine vs. fluoxetine. Zhejiang Medical
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Huang 2007 {published data only}
Huang X-J, Gong M-E, Tang Z-Y. Comparison of
mirtazapine and paroxetine in patients with first-episode
climacteric depression. Chinese Mental Health Journal 2007;
21(6):428–30.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
31
Kang 2009 {published data only}
Kang E-H, Lee I-S, Chung S-K, Lee S-Y, Kim E-J, Hong
J-P, et al. Mirtazapine versus venlafaxine for the treatment
of somatic symptoms associated with major depressive
disorder: A randomized, open-labelled trial. Psychiatry
Research 2009;169(2):118–23.
Kim 2011 {published data only}
Kim JE, Yoon SJ, Kim J, Jung JY, Jeong HS, Cho HB,
et al. Efficacy and tolerability of mirtazapine in treating
major depressive disorder with anxiety symptoms: An 8week open-label randomised paroxetine-controlled trial.
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Li 2005 {published data only}
Li Jing, Meng Hua-Qing, Deng Wei. Mirtazapine and
fluoxetine in the treatment of cardiovascular neurosis with
depression. Chinese Mental Health Journal 2005;19(9):
637–9.
Liang 2006 {published data only}
Liang K. Comparative study of mirtazapine and sertraline
in treatment of elderly depressive patient. Journal of Heze
Medical College 2006;18(2):5–7.
Lin 2005 {published data only}
Lin Z, Chen Y. A study of mirtazapine and paroxetine in
the treatment of anxiety. Sichuan Medical Journal 2005;26
(11):1229–30.
Liu 2004 {published data only}
Liu P. A study of mirtazapine and venlafaxine in the
treatment of depression. Health Psychology Journal 2004;12
(1):15–6.
Ma 2003 {published data only}
Ma ZW, Li MX, Yang FS, et al. Comparative study on
the efficacy and safety of mirtazapine and amitriptyline in
treatment of depression. Chinese Journal of New Drugs
2003;12(10):858–60.
Ning 2004 {published data only}
Ning J, Lu D. Observation of the clinical efficacy and
safety of mirtazapine on elder depression treatment. Clnical
Pharmaceuticals 2004;13(5):63–4.
Niu 2004 {published data only}
Niu F, Shen X, Sun S. Comparison of efficacy of mirtazapine
and fluoxetine in treatment of depression with generalized
anxiety disorder. Chinese Journal of New Drugs and Clinical
Remedies 2004;23(12):853–5.
Paslakis 2010 {published data only}
Paslakis G, Luppa P, Gilles M, Kopf D, Hamann Weber B,
Lederbogen F, et al. Venlafaxine and mirtazapine treatment
lowers serum concentrations of dehydroepiandrosteronesulfate in depressed patients remitting during the course
of treatment. Journal of Psychiatric Research 2010;44(8):
556–60.
Peng 2004 {published data only}
Peng J, Xu Y, Piao S, et al. A comparative study of
mirtazapine and paroxetine for depressed patients. Medical
Journal of Chinese People Health 2004;16(11):664–5.
Ren 2004 {published data only}
Ren H, Guo Q, Cheng M. A study of mirtazapine and
paroxetine in the treatment of depression. Journal of Clinical
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Sarginson 2010 {published data only}
Sarginson JE, Lazzeroni LC, Ryan HS, Ershoff BD,
Schatzberg AF, Murphy GM Jr. ABCB1 (MDR1)
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Scharnholz 2010 {published data only}
Scharnholz B, Weber-Hamann B, Lederbogen F, Schilling
C, Gilles M, Onken V, et al. Antidepressant treatment
with mirtazapine, but not venlafaxine, lowers cortisol
concentrations in saliva: A randomised open trial. Psychiatry
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Su 2005 {published data only}
Su H, Lei D, Yu H. Comparative study of mirtazapine and
paroxetine in the treatment of depression. Modern Medicine
and Health 2005;21(12):1480–1.
Tang 2005 {published data only}
Tang Z, Li M. Mirtazapine compared with paroxetine in
depressed patients with anxiety symptoms. Chinese Mental
Health Journal 2005;19(9):643–5.
Tao 2004 {published data only}
Tao M, Gao JF, Tang WX, et al. Clinical efficacy and
compliance of mirtazapine in the treatment of depression.
Chinese Mental Health Journal 2004;18(5):360–2.
Wang 2006 {published data only}
Wang A, Zhu W. Efficacy and safety of mirtazapine versus
clomipramine in patients with depression and anxiety.
Shanghai Archives of Psychiatry 2006;18(1):24–6.
Weng 2001 {published data only}
Weng S, Li H, Zhao J, Zhang H, Li T, Shu L, et al.
Mirtazapine vs. fluoxetine in treatment of major depressive
disorder: a multicenter clinical trial. Chinese Journal of New
Drugs and Clinical Remedies 2001;20(5):329–33.
Wu 2006 {published data only}
Wu Y. Controlled study of mirtazapine vs. venlafaxine in the
treatment of depression. Journal of Clinical Psychosomatic
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Xie 2002 {published data only}
Xie K. Venlafaxine vs buspirone in treating depression
associated with anxiety. Health Psychology Journal 2002;10
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Xie 2004 {published data only}
Xie N, Yan Y, Di L, et al. A comparative study of
mirtazapine and efexor XR for depressive patients. Medical
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Xie 2004a {published data only}
Xie N, Zhao H, Di L, et al. A comparative study of
mirtazapine and fluoxetine for depressive patients. Sichuan
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Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
32
Xie 2005 {published data only}
Xie K, Hai Y, Zhang D, et al. A comparative study of
venlafaxine, maprotiline and buspirone in the treatment of
depression. Chinese Journal of Health Psychology 2005;13(1):
71–3.
Xiong 2003 {published data only}
Xiong P, Xuan X, Wang J. A comparative study of
mirtazapine and imipramine for depressive patients.
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Yang 2005 {published data only}
Yang L, Yang K, Li Y. Clinical comparative study on
mirtazapine and venlafaxine used in treating depression.
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Yao 2006 {published data only}
Yao X. Study of the treatment of depression with
mirtazapine, trazodone and maprotiline. Chinese Journal of
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Ye 2005 {published data only}
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Yu 2004 {published data only}
Yu G, Ding G, Li X. Mirtazapine and amitriptyline in the
maintenance treatment of depressed patients: Comparison
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Zhang 2003 {published data only}
Zhang J, Liu T, Zhao J, et al. The control study of
mirtazapine versus fluoxetine in the treatment of depression.
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Zhang 2003a {published data only}
Zhang J, Liu T, Zhao J, Hao W, Xie G, Su L, et al.
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Zhang 2004 {published data only}
Zhang J, Wang Y, Li Z. A controlled study of mirtazapine
and amitriptyline in depression. Journal of Clinical
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Zheng 2005 {published data only}
Zheng H. Control study on clinical effect of mirtazapine in
treatment depression. Chinese Journal of Health Psychology
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Zhu 2003 {published data only}
Zhu H, Yu J, Zheng H. A study of switching to mirtazapine
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Zhu 2005 {published data only}
Zhu J, Jiang X, Zhou D, Zhang F. Comparative study of
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Zhu 2006 {published data only}
Zhu J. Comparative study of mirtazapine and fluoxetine in
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Zou 2006 {published data only}
Zou J, Jing Y, Song K, Hu Y. Comparative study on
mirtazapine and paroxetine in the treatment of depression.
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Psychopharmacology 2010;25(4):189–98.
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References to other published versions of this review
Watanabe 2008
Watanabe N, Omori IM, Nakagawa A, Cipriani A,
Barbui C, McGuire H, et al. Mirtazapine versus other
antidepressants in the acute-phase treatment of adults with
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Watanabe 2010
Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui
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[DOI: 10.2165/11319480-000000000-00000]
∗
Indicates the major publication for the study
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
37
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Amini 2005
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: In- and outpatients
Interventions
1. Mirtazapine: 30 mg/day, N = 18
2. Fluoxetine: 20 mg/day, N = 18
Fixed dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: None
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of concealment is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
Low risk
Less than 20% of the participants dropped
out and missing outcome data are balanced
in numbers across intervention groups, with
similar reasons of missing data across groups
Selective reporting (reporting bias)
Low risk
Both the response and the remission outcomes are reported in the figures with the actual numbers of the participants who achieved
these
Free of Sponsorship bias?
Unclear risk
The funding source is not described.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
38
Behnke 2003
Methods
8 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Unclear
Interventions
1. Mirtazapine: 30-45 mg/day, N = 176
2. Sertraline: 50-150 mg/day, N = 170
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, CGI-Improvement, CGI-Severity
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of concealment is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
Both the response and the remission outcomes are reported in the figures with the actual numbers of the participants who achieved
these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Benkert 2000
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
39
Benkert 2000
(Continued)
Interventions
1. Mirtazapine: 15-45 mg/day, N = 139
2. Paroxetine: 20-40 mg/day, N = 136
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: HAM-A, BDI, Welzil-Kohnen Colored Scales, Short Form-36, CGIImprovement, CGI-severity
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of concealment is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
Both the response and the remission outcomes
at end of the acute-phase treatment are reported with the proportion of the participants
who achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Benkert 2006
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients
Interventions
1. Mirtazapine: 45 mg/day, N = 130
2. Venlafaxine: 225 mg/day, N = 128
Fixed dosing scheduling
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
40
Benkert 2006
(Continued)
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, CGI-Improvement, CGI-Severity
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of concealment is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
Both the response and the remission outcomes
at end of the acute-phase treatment are reported with the proportion of the participants
who achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Bremner 1995
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: Outpatients
Interventions
1. Mirtazapine: 5-35 mg/day, N = 50
2. Amitriptlyline: 40-280 mg/day, N = 50
3. Placebo, N = 50
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, CGI-Improvement, CGI-Severity, Zung Self-Rating Depression Scale
Notes
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
41
Bremner 1995
(Continued)
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of concealment is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
Low risk
Less than 20% of the participants dropped
out and missing outcome data are balanced
in numbers across intervention groups, with
similar reasons of missing data across groups
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Brunnauer 2008
Methods
2 week randomised study
Participants
Diagnosis: DSM-IV major depressive disorder, single episode
Setting: Psychiatric inpatients
Interventions
1. Mirtazapine: mean 38.2 (SD 9.0) mg/day, N = 20
2. Reboxetine: mean 6.6 (SD 1.9) mg/day, N = 20
Flexible dosing scheduling
Outcomes
The measure used for primary outcome: Performance in driving simulator
Other measures: HAM-D, BDI
Notes
Only information about attrition of the participants is available for the present review
Risk of bias
Bias
Authors’ judgement
Support for judgement
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
42
Brunnauer 2008
(Continued)
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Comment: The method of concealment is not described.
Unclear risk
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
Low risk
Less than 20% of the participants dropped out and missing
outcome data are balanced in numbers across intervention
groups, with similar reasons of missing data across groups
Selective reporting (reporting bias)
Unclear risk
No useful information in terms of depression severity at the
end of treatment is provide
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical company of the
comparator drug
Debonnel 2000a
Methods
4 week randomised study
Participants
Diagnosis: DSM-IV major depression
Setting: Unclear
Interventions
1. Mirtazapine: 30-45 mg/day, N = 20
2. Paroxetine: 20-30 mg/day, N = 20
3. Combination of mirtazapine and paroxetine
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: Unclear
Other measures: MADRS
Notes
We were unable to retrieve usable information for the meta-analysis and to contact the
author because the principal author passed away
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Comment: The method of concealment is not described.
Unclear risk
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
43
Debonnel 2000a
(Continued)
Blinding (performance bias and detection Low risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk
No information of attrition to permit judgement is provided.
Selective reporting (reporting bias)
Unclear risk
No information to permit judgement is provided.
Free of Sponsorship bias?
Unclear risk
No information to permit judgement is provided.
Fava 2006
Methods
14 week randomised study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients
Interventions
1. Mirtazapine: 15-60 mg/day, N = 114
2. Nortriptyline: 25-150 mg/day, N = 121
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 16-item Quick Inventory
of Depressive Symptomatology
Other measures: 17-item HAM-D, Short-Form Health Survey, Work Productivity and
Activity Impairment Questionnaire, Work and Social Adjustment Scale, Quality of Life
Enjoyment and Satisfaction Questionnaire
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “random assignment”
Comment: No further information provided.
Allocation concealment (selection bias)
Comment: The method of concealment is not described.
Unclear risk
Blinding (performance bias and detection High risk
bias)
All outcomes
Comment: Both the participants and the clinicians knew
the treatment status
Incomplete outcome data (attrition bias)
All outcomes
No information of attrition to permit judgement is provided.
Unclear risk
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
44
Fava 2006
(Continued)
Selective reporting (reporting bias)
Low risk
Both the response and the remission outcomes are reported
in figures with the proportion of the participants who
achieved these
Free of Sponsorship bias?
Low risk
The funding source is National Institute of Mental Health.
Guelfi 2000
Methods
8 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Inpatients
Interventions
1. Mirtazapine: 45-60 mg/day, N = 78
2. Venlafaxine: 75-375 mg/day, N = 79
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: The Quality of Life, Enjoyment, and Satisfaction Questionnaire and
Quality of Life in Depression Scale, Quality of Life in Depression Scales
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Quote: “participants were randomised to receive treatment with either mirtazapine or
venlafaxine orally for 8 weeks, prepared as indistinguishable capsules, according to a centrally prepared randomization list”
Comment: No further information about actual central randomisation provided
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
High risk
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
45
Guelfi 2000
(Continued)
Selective reporting (reporting bias)
Low risk
Both the response and the remission outcomes
at end of the acute-phase treatment are reported with the proportion of the participants
who achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Halikas 1995
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: Outpatients over 55 years of age
Interventions
1. Mirtazapine: 5-35 mg/day, N = 50
2. Trazodone: 40-280 mg/day, N = 50
3. Placebo, N = 50
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 21-item HAM-D
Other measures: MADRS, CGI-Severity, Zung Self-Rating Scale for Depression
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
46
Halikas 1995
(Continued)
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Hong 2003
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients
Interventions
1. Mirtazapine: 15-40 mg/day, N = 66
2. Fluoxetine: 20-40 mg/day, N = 66
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: CGI-Severity
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response and remission outcomes at the
end of acute-phase treatment are provided
as the proportion of the participants who
achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
47
Hoyberg 1996
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: In- and outpatients
Interventions
1. Mirtazapine: 15-45 mg/day, N = 56
2. Amitriptyline: 30-90 mg/day, N = 59
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 21-item HAM-D
Other measures: MADRS, CGI-Improvement, CGI-Severity, Brief Cognitive Rating
Scale
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to the mirtazapine arm dropped out during
the study
Selective reporting (reporting bias)
High risk
Neither the response or remission outcomes at
the end of acute-phase treatment are provided.
They needed to be imputed in the analysis
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Leinonen 1999
Methods
8 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: In- and outpatients
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
48
Leinonen 1999
(Continued)
Interventions
1. Mirtazapine: 15-40 mg/day, N = 66
2. Fluoxetine: 20-40 mg/day, N = 66
Flexiblie dosing scheduling
Outcomes
The measure used for response and remission in the review: MADRS
Other measures: HAM-A, CGI-Improvement, CGI-Severity, Leeds Sleep Evaluation
Questionnaire -adapted, Quality of Life Enjoyment and Satisfaction Questionnaire
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Quote: “participants were allocated to treatment with either mirtazapine or citalopram,
according to the centrally prepared randomization list”
Comment: No further information about actual central randomisation provided
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
Low risk
Less than 20% of the participants dropped
out and missing outcome data are balanced
in numbers across intervention groups, with
similar reasons of missing data across groups
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Marttila 1995
Methods
6 week randomised double blind study
Participants
Diagnosis: Research Diagnostic criteria major depressive disorder
Setting: In- and outpatients
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
49
Marttila 1995
(Continued)
Interventions
1. Mirtazapine: 20-60 mg/day, N =83
2. Doxepin: 75-300 mg/day, N = 80
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, Brief Psychiatric Rating Scale, Global Assessment Score, Beck
Depression Inventory, Newcastle Endogenous / Reactive Depression Rating Scale
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to the comparator arm dropped out during
the study
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Mullin 1996
Methods
5 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: In- and outpatients
Interventions
1. Mirtazapine: 20-60 mg/day, N = 79
2. Amitriptyline: 75-225 mg/day, N = 77
Flexible dosing scheduling
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
50
Mullin 1996
(Continued)
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, Brief Psychiatric Rating Scale, General Assessment Scale
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to the comparator arm dropped out during
the study
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Organon 85146
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: Inpatients
Interventions
1. Mirtazapine: 20-60 mg/day, N = 103
2. Amitriptyline: 75-225 mg/day, N = 104
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, CGI-Improvement
Notes
Risk of bias
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
51
Organon 85146
(Continued)
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomly allocated”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Richou 1995
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Inpatients
Interventions
1. Mirtazapine: 20-80 mg/day, N = 87
2. Clomipramine: 50-200 mg/day, N = 87
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 21-item HAM-D
Other measures: MADRS, Brief Psychiatric Rating Scale, General Assessment Scale
Notes
Risk of bias
Bias
Authors’ judgement
Random sequence generation (selection Unclear risk
bias)
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Support for judgement
Quote: “randomly allocated”
Comment: No further information provided.
52
Richou 1995
(Continued)
Allocation concealment (selection bias)
Unclear risk
Comment: The method of concealment is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Schatzberg 2002
Methods
8 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients
Interventions
1. Mirtazapine: 15-40 mg/day, N = 128
2. Paroxetine: 20-40 mg/day, N = 126
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: CGI-Severity, CGI-Improvement
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The information of concealment
is not described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
53
Schatzberg 2002
(Continued)
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to the comparator arm dropped out during
the study
Selective reporting (reporting bias)
Low risk
The response and remission outcomes at the
end of acute-phase treatment are provided
as the proportion of the participants who
achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Schoemaker 2002
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients
Interventions
1. Mirtazapine: 15-45 mg/day, N = 205
2. Fluvoxamine: 50-150 mg/day, N = 207
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: 21-item HAM-D
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
More than 20% of the allocated participants
to the comparator arm dropped out during
the study
High risk
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
54
Schoemaker 2002
(Continued)
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Schule 2006
Methods
5 week randomised study
Participants
Diagnosis: DSM-IV major depressive episode (bipolar disorder not included)
Setting: Psychiatric inpatients
Interventions
1. Mirtazapine: 45 mg/day, N = 20
2. Reboxetine: 8 mg/day, N = 20
Fixed dosing scheduling
Outcomes
The measure used for response and remission in the review: 21-item HAM-D
Other measures: Hypothalamic-pituitary-adrenocortical axis activity
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Comment: The method of allocation is not described.
Unclear risk
Blinding (performance bias and detection High risk
bias)
All outcomes
Quote: “We abstained from blinding the medication because the side effect profiles of reboxetine and mirtazapine
markedly differ”
Incomplete outcome data (attrition bias)
All outcomes
Low risk
Less than 20% of the participants dropped out and missing
outcome data are balanced in numbers across intervention
groups, with similar reasons of missing data across groups
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acute-phase treatment
is provided as the numbers of the participants who achieved
this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical company of mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
55
Smith 1990
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: Outpatients
Interventions
1. Mirtazapine: -35 mg/day, N = 50
2. Amitriptyline: -280 mg/day, N = 50
3. Placebo, N = 50
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, CGI-Improvement, CGI-Severity, Zung Self-Rating Depression Scale
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk
The numbers of dropouts in the both arms are
not specified.
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Thase 2000
Methods
8 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
56
Thase 2000
(Continued)
Interventions
1. Mirtazapine: 15-45 mg/day, N = 124
2. Sertraline: 50-200 mg/day, N = 126
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: Inventory of Depressive Symptomatology - Self-Report Scale, Social
Adaptation Self-evaluation Scale, CGI-Severity, CGI-Efficacy
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response and remission outcomes at the
end of acute-phase treatment are provided
as the proportion of the participants who
achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Turan 2000a
Methods
60 day randomised study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Unclear
Interventions
1. Mirtazapine: unclear dose, N = 25
2. Amitriptyline: unclear dose, N = 27
Flexible dosing scheduling
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
57
Turan 2000a
(Continued)
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, CGI-I
Notes
We were unable to retrieve usable information for the meta-analysis and to obtain replies
from the author
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Comment: The method of concealment is not described.
Unclear risk
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
No information to permit judgement is provided.
Incomplete outcome data (attrition bias)
All outcomes
Low risk
Less than 20% of the participants dropped out and missing
outcome data are balanced in numbers across intervention
groups, with similar reasons of missing data across groups
Selective reporting (reporting bias)
Unclear risk
No information to permit judgement is provided.
Free of Sponsorship bias?
Unclear risk
No information to permit judgement is provided.
van Moffaert 1995
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: Inpatients
Interventions
1. Mirtazapine: 24-72 mg/day, N = 100
2. Trazodone: 150-450 mg/day, N = 100
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, Brief Psychiatric Rating Scale, General Psychiatric Impression
Global Assessment Scale, Beck Depression Inventory
Notes
Risk of bias
Bias
Authors’ judgement
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Support for judgement
58
van Moffaert 1995
(Continued)
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Versiani 2005
Methods
8 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: In- and outpatients
Interventions
1. Mirtazapine: 30-60 mg/day, N = 147
2. Fluoxetine: 20-40 mg/day, N = 152
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: MADRS, CGI-Severity, Leeds Sleep Evaluation Questionnaire, Quality of Life, Enjoyment and Satisfaction Questionnaire, Changes in Sezual Functioning
Questionnaire
Notes
Risk of bias
Bias
Authors’ judgement
Random sequence generation (selection Unclear risk
bias)
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Support for judgement
Quote: “randomised”
Comment: No further information provided.
59
Versiani 2005
(Continued)
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk
The numbers of dropouts in the both arms are
not specified.
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided in the figure as the
proportion of the participants who achieved
this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Wade 2003
Methods
24 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Outpatients (in general practitioner clinics)
Interventions
1. Mirtazapine: 30-45 mg/day, N = 99
2. Paroxetine: 20-30 mg/day, N = 98
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: CGI-Improvement, CGI-Severity, CGI-Patient Global Evaluation
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Quote: “Randomization was performed according to centrally prepared randomization
lists”
Comment: No further information about actual central randomization provided
Unclear risk
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
60
Wade 2003
(Continued)
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response and remission outcomes at the
end of acute-phase treatment are provided in
the figures as the proportion of the participants who achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Wheatley 1998
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III-R major depressive disorder
Setting: In- and outpatients
Interventions
1. Mirtazapine: 15-60 mg/day, N = 66
2. Fluoxetine: 20-40 mg/day, N = 67
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 17-item HAM-D
Other measures: CGI-Severity, the Visual Analogue Mood Rating Scale, Quality of Life
Enjoyment and Satisfaction Questionnaire
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Quote: “participants were allocated to treatment with either mirtazapine or fluoxetine,
according to the centrally prepared randomization list”
Comment: No further information about actual central randomization provided
Unclear risk
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
61
Wheatley 1998
(Continued)
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
Selective reporting (reporting bias)
Low risk
The response and remission outcomes at the
end of acute-phase treatment are provided in
the figures as the proportion of the participants who achieved these
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Winokur 2003
Methods
8 week randomised double blind study
Participants
Diagnosis: DSM-IV major depressive disorder
Setting: Unclear
Interventions
1. Mirtazapine: 45 mg/day, N = 9
2. Fluoxetine: 40 mg/day, N = 13
Fixed dosing scheduling
Outcomes
The measure used for response and remission in the review: 21-item HAM-D
Other measures: CGI-Severity, polysomnographic data, multiple sleep latency testing,
performance vigilance testing, Epworth Sleepiness Scale
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomly assigned”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
62
Winokur 2003
(Continued)
Incomplete outcome data (attrition bias)
All outcomes
High risk
More than 20% of the allocated participants
to the comparator arm dropped out during
the study
Selective reporting (reporting bias)
High risk
Neither the response nor remission outcomes
at the end of acute-phase treatment are provided. They needed to be imputed in the analysis
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Zivkov 1995
Methods
6 week randomised double blind study
Participants
Diagnosis: DSM-III major depressive disorder
Setting: Inpatients
Interventions
1. Mirtazapine: 20-60 mg/day, N = 125
2. Amitriptyline: 75-225 mg/day, N = 126
Flexible dosing scheduling
Outcomes
The measure used for response and remission in the review: 21-item HAM-D
Other measures; Brief Psychiatric Rating Scale, General Assessment Scale
Notes
Risk of bias
Bias
Authors’ judgement
Support for judgement
Random sequence generation (selection Unclear risk
bias)
Quote: “randomised”
Comment: No further information provided.
Allocation concealment (selection bias)
Unclear risk
Comment: The method of allocation is not
described.
Blinding (performance bias and detection Unclear risk
bias)
All outcomes
Quote: “double-blind”
Comment: No further information provided.
Incomplete outcome data (attrition bias)
All outcomes
More than 20% of the allocated participants
to both of the intervention arms dropped out
during the study
High risk
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
63
Zivkov 1995
(Continued)
Selective reporting (reporting bias)
Low risk
The response outcome at the end of acutephase treatment is provided as the proportion
of the participants who achieved this
Free of Sponsorship bias?
High risk
The funding source is the pharmaceutical
company of mirtazapine
Abbreviations: CGI = Clinical Global Impression, HAM-D = Hamilton Rating Scale for Depression, MADRS = Montgomery-Asberg
Depression Rating Scale, RDC = Research Diagnostic Criteria
Characteristics of excluded studies [ordered by study ID]
Study
Reason for exclusion
Blier 2004
Mirtazapine was combined with another antidepressant.
Bruijin 1996
A review of other studies.
Kasper 1997a
A review of other studies.
Kasper 1997b
A review of other studies.
Kremer 1995
Not a relevant diagnostic status.
Peyron 1996
Not a relevant diagnostic status.
Tulen 1996
Not a relevant diagnostic status.
Zourkova 2001
Not employing random allocation.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
64
DATA AND ANALYSES
Comparison 1. Mirtazapine versus TCAs
Outcome or subgroup title
1 Primary outcome (response) at 2
weeks
1.1 vs Amitriptyline
1.2 vs Clomipramine
1.3 vs Doxepin
1.4 vs Nortriptyline
2 Primary outcome (response)
at end of the acute-phase
treatment
2.1 vs Amitriptyline
2.2 vs Clomipramine
2.3 vs Doxepin
2.4 vs Nortriptyline
3 Secondary outcome (remission)
at 2 weeks
3.1 vs Amitriptyline
3.2 vs Clomipramine
3.3 vs Doxepin
3.4 vs Nortriptyline
4 Secondary outcome (remission)
at end of the acute-phase
treatment
4.1 vs Amitriptyline
4.2 vs Clomipramine
4.3 vs Doxepin
4.4 vs Nortriptyline
5 Secondary outcome (depression
severity) at 2 weeks
5.1 vs Amitritpyline
6 Secondary outcome (depression
severity) at end of the
acute-phase treatment
6.1 vs Amitritpyline
7 Secondary outcome (Social
adjustment) at 2 weeks
7.1 vs Amitriptyline
8 Secondary outcome (Social
adjustment) at end of the
acute-phase treatment
8.1 vs Amitriptyline
8.2 vs Clomipramine
8.3 vs Doxepin
No. of
studies
No. of
participants
8
1294
Odds Ratio (M-H, Random, 95% CI)
0.85 [0.64, 1.13]
5
1
1
1
9
722
174
163
235
1501
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.77 [0.54, 1.12]
0.89 [0.46, 1.73]
1.11 [0.58, 2.12]
0.84 [0.22, 3.22]
0.89 [0.72, 1.10]
6
1
1
1
8
929
174
163
235
1294
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.90 [0.69, 1.17]
0.90 [0.47, 1.71]
0.85 [0.44, 1.63]
0.91 [0.53, 1.55]
0.85 [0.55, 1.32]
5
1
1
1
9
722
174
163
235
1501
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.67 [0.35, 1.29]
0.89 [0.34, 2.31]
1.27 [0.54, 3.00]
0.70 [0.12, 4.28]
0.86 [0.69, 1.08]
6
1
1
1
2
929
174
163
235
361
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)
0.87 [0.65, 1.16]
0.77 [0.41, 1.45]
0.94 [0.50, 1.74]
0.85 [0.46, 1.56]
0.10 [-0.11, 0.31]
2
1
361
144
Std. Mean Difference (IV, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)
0.10 [-0.11, 0.31]
0.12 [-0.21, 0.45]
1
1
144
138
Std. Mean Difference (IV, Random, 95% CI)
Mean Difference (IV, Random, 95% CI)
0.12 [-0.21, 0.45]
1.60 [-1.98, 5.18]
1
3
138
440
Mean Difference (IV, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)
1.60 [-1.98, 5.18]
0.02 [-0.17, 0.21]
1
1
1
114
163
163
Std. Mean Difference (IV, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)
0.03 [-0.34, 0.40]
0.12 [-0.19, 0.43]
-0.09 [-0.39, 0.22]
Statistical method
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Effect size
65
9 Secondary outcome (withdrawal
due to any reason)
9.1 vs Amitriptyline
9.2 vs Clomipramine
9.3 vs Doxepin
10 Secondary outcome
(withdrawal due to adverse
events)
10.1 vs Amitriptyline
10.2 vs Clomipramine
10.3 vs Doxepin
11 Secondary outcome (having
some adverse events)
11.1 vs Amitriptyline
11.2 vs Nortriptyline
12 Hypertension/Tachycardia
12.1 vs Amitriptyline
13 Hypotension/Bradycardia
13.1 vs Amitriptyline
14 Sweating
14.1 vs Amitriptyline
15 Constipation
15.1 vs Amitriptyline
15.2 vs Clomipramine
16 Dry mouth/Decreased
salivation
16.1 vs Amitriptyline
16.2 vs Clomipramine
16.3 vs Doxepin
17 Nausea/Vomiting/Gastric
distress
17.1 vs Amitriptyline
17.2 vs Clomipramine
18 Weight gain/Increased appetite
18.1 vs Amitriptyline
19 Sexual dysfunction
19.1 vs Amitriptyline
20 Anxiety/Agitation
20.1 vs Amitriptyline
21 Dizziness/Vertigo/Faintness
21.1 vs Amitriptyline
21.2 vs Clomipramine
21.3 vs Doxepin
22 Fatigue/Tiredness/Asthenia
22.1 vs Amitriptyline
23 Headache
23.1 vs Amitriptyline
24 Tremor
24.1 vs Amitriptyline
24.2 vs Clomipramine
25 Sleep disturbance
25.1 vs Amitriptyline
7
1166
Odds Ratio (M-H, Random, 95% CI)
0.83 [0.63, 1.10]
5
1
1
8
829
174
163
1266
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.90 [0.65, 1.25]
0.80 [0.42, 1.54]
0.51 [0.22, 1.19]
0.65 [0.41, 1.03]
6
1
1
2
929
174
163
442
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.60 [0.35, 1.03]
1.14 [0.42, 3.10]
0.30 [0.06, 1.56]
1.06 [0.54, 2.10]
1
1
4
4
2
2
2
2
6
5
1
8
207
235
522
522
215
215
458
458
1003
829
174
1266
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.74 [0.16, 3.37]
1.17 [0.55, 2.49]
0.44 [0.24, 0.81]
0.44 [0.24, 0.81]
0.46 [0.12, 1.81]
0.46 [0.12, 1.81]
0.42 [0.05, 3.24]
0.42 [0.05, 3.24]
0.72 [0.46, 1.12]
0.72 [0.40, 1.29]
0.62 [0.26, 1.48]
0.52 [0.24, 1.14]
6
1
1
4
929
174
163
581
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.36 [0.14, 0.92]
0.81 [0.39, 1.69]
2.86 [1.18, 6.94]
0.29 [0.05, 1.59]
3
1
3
3
2
2
2
2
7
5
1
1
4
4
4
4
7
6
1
1
1
407
174
463
463
351
351
307
307
1166
829
174
163
673
673
522
522
1103
929
174
207
207
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.33 [0.04, 2.59]
0.16 [0.02, 1.33]
1.04 [0.58, 1.86]
1.04 [0.58, 1.86]
0.41 [0.06, 2.61]
0.41 [0.06, 2.61]
0.87 [0.34, 2.19]
0.87 [0.34, 2.19]
0.75 [0.43, 1.28]
0.64 [0.35, 1.17]
0.70 [0.21, 2.29]
3.04 [0.59, 15.53]
1.25 [0.71, 2.21]
1.25 [0.71, 2.21]
0.74 [0.31, 1.74]
0.74 [0.31, 1.74]
0.36 [0.22, 0.57]
0.36 [0.20, 0.62]
0.36 [0.15, 0.88]
1.43 [0.69, 2.98]
1.43 [0.69, 2.98]
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
66
26 Sleepiness/Drowsiness/
Somnolence
26.1 vs Amitriptyline
26.2 vs Doxepin
27 Suicide attempt
27.1 vs Amitriptyline
27.2 vs Clomipramine
27.3 vs Doxepin
27.4 vs Nortriptyline
28 Subgroup analysis: Response at
2 weeks: Treatment settings:
Psychiatric inpatients
28.1 vs Amitriptyline
28.2 vs Clomipramine
29 Subgroup analysis: Response
at end of the acute-phase
treatment: Treatment settings:
Psychiatric inpatients
29.1 vs Amitriptyline
29.2 vs Clomipramine
30 Sensitivity analysis: Response
at 2 weeks: Studies without
imputation
30.1 vs Amitriptyline
30.2 vs Clomipramine
30.3 vs Doxepin
30.4 vs Nortriptyline
31 Sensitivity analysis: Response
at end of the acute-phase
treatment: Studies without
imputation
31.1 vs Amitriptyline
31.2 vs Clomipramine
31.3 vs Doxepin
31.4 vs Nortriptyline
32 Secondary outcome (SKEWED
DATA: depression severity) at
2 weeks
33 Secondary outcome (SKEWED
DATA: depression severity)
at end of the acute-phase
treatment
6
841
Odds Ratio (M-H, Random, 95% CI)
0.92 [0.66, 1.27]
5
1
5
2
1
1
1
2
678
163
935
363
174
163
235
425
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.81 [0.58, 1.14]
1.86 [0.82, 4.21]
1.77 [0.47, 6.58]
2.08 [0.27, 16.29]
1.0 [0.06, 16.25]
0.32 [0.01, 7.91]
9.90 [0.53, 185.90]
0.81 [0.50, 1.32]
1
1
3
251
174
632
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.73 [0.36, 1.48]
0.89 [0.46, 1.73]
0.89 [0.64, 1.23]
2
1
7
458
174
1179
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.88 [0.60, 1.29]
0.90 [0.47, 1.71]
0.85 [0.64, 1.15]
4
1
1
1
8
607
174
163
235
1386
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.76 [0.51, 1.13]
0.89 [0.46, 1.73]
1.11 [0.58, 2.12]
0.84 [0.22, 3.22]
0.93 [0.74, 1.15]
5
1
1
1
814
174
163
235
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Other data
0.95 [0.72, 1.26]
0.90 [0.47, 1.71]
0.85 [0.44, 1.63]
0.91 [0.53, 1.55]
No numeric data
Other data
No numeric data
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
67
Comparison 2. Mirtazapine versus SSRIs
Outcome or subgroup title
1 Primary outcome (response) at 2
weeks
1.1 vs Citalolpram
1.2 vs Fluoxetine
1.3 vs Paroxetine
1.4 vs Sertraline
1.5 vs Fluvoxamine
2 Primary outcome (response)
at end of the acute-phase
treatment
2.1 vs Citalolpram
2.2 vs Fluoxetine
2.3 vs Paroxetine
2.4 vs Sertraline
2.5 vs Fluvoxamine
3 Primary outcome (response)
at end of the continuation
treatment
3.1 vs Paroxetine
4 Secondary outcome (remission)
at 2 weeks
4.1 vs Citalolpram
4.2 vs Fluoxetine
4.3 vs Paroxetine
4.4 vs Sertraline
4.5 vs Fluvoxamine
5 Secondary outcome (remission)
at end of the acute-phase
treatment
5.1 vs Citalolpram
5.2 vs Fluoxetine
5.3 vs Paroxetine
5.4 vs Sertraline
5.5 vs Fluvoxamine
6 Secondary outcome (remission)
at end of the continuation
treatment
6.1 vs Paroxetine
7 Secondary outcome (withdrawal
due to any reason)
7.1 vs Citalolpram
7.2 vs Fluoxetine
7.3 vs Paroxetine
7.4 vs Sertraline
7.5 vs Fluvoxamine
No. of
studies
No. of
participants
12
2626
Odds Ratio (M-H, Random, 95% CI)
1.57 [1.30, 1.88]
1
5
3
2
1
12
270
622
726
596
412
2626
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
2.01 [0.93, 4.35]
1.26 [0.86, 1.85]
2.39 [1.42, 4.02]
1.45 [1.04, 2.02]
1.38 [0.90, 2.13]
1.19 [1.01, 1.39]
1
5
3
2
1
1
270
622
726
596
412
197
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.76 [0.38, 1.52]
1.55 [1.07, 2.23]
1.27 [0.94, 1.70]
0.97 [0.70, 1.35]
1.14 [0.76, 1.70]
1.60 [0.91, 2.81]
1
12
197
2626
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.60 [0.91, 2.81]
1.82 [1.36, 2.44]
1
5
3
2
1
12
270
622
726
596
412
2626
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
2.48 [0.47, 13.02]
1.63 [0.81, 3.27]
2.31 [1.04, 5.11]
1.94 [1.19, 3.15]
1.46 [0.77, 2.76]
1.17 [0.98, 1.40]
1
5
3
2
1
1
270
622
726
596
412
197
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.92 [0.55, 1.52]
1.12 [0.80, 1.57]
1.58 [1.16, 2.15]
1.18 [0.82, 1.71]
0.84 [0.57, 1.23]
1.89 [1.01, 3.54]
1
11
197
2327
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.89 [1.01, 3.54]
1.12 [0.89, 1.40]
1
4
3
2
1
270
323
726
596
412
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
2.36 [0.99, 5.64]
1.09 [0.67, 1.78]
0.80 [0.58, 1.10]
1.47 [1.01, 2.13]
1.20 [0.75, 1.93]
Statistical method
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Effect size
68
8 Secondary outcome (withdrawal
due to adverse events)
8.1 vs Citalolpram
8.2 vs Fluoxetine
8.3 vs Paroxetine
8.4 vs Sertraline
8.5 vs Fluvoxamine
9 Secondary outcome (having
some adverse events)
9.1 vs Citalolpram
9.2 vs Fluoxetine
9.3 vs Paroxetine
9.4 vs Sertraline
10 Hypotension/Bradycardia
10.1 vs Fluoxetine
11 Sweating
11.1 vs Citalolpram
11.2 vs Paroxetine
11.3 vs Sertraline
12 Constipation
12.1 vs Fluoxetine
12.2 vs Paroxetine
12.3 vs Fluvoxamine
13 Diarrhoea
13.1 vs Citalolpram
13.2 vs Fluoxetine
13.3 vs Paroxetine
13.4 vs Sertraline
13.5 vs Fluvoxamine
14 Dry mouth/Decreased
salivation
14.1 vs Citalolpram
14.2 vs Fluoxetine
14.3 vs Paroxetine
14.4 vs Sertraline
14.5 vs Fluvoxamine
15 Nausea/Vomiting/Gastric
distress
15.1 vs Citalolpram
15.2 vs Fluoxetine
15.3 vs Paroxetine
15.4 vs Sertraline
15.5 vs Fluvoxamine
16 Weight gain/Increased appetite
16.1 vs Citalolpram
16.2 vs Fluoxetine
16.3 vs Paroxetine
16.4 vs Sertraline
16.5 vs Fluvoxamine
17 Weight loss/Anorexia
17.1 vs Fluoxetine
17.2 vs Paroxetine
11
2604
Odds Ratio (M-H, Random, 95% CI)
1.26 [0.85, 1.86]
1
4
3
2
1
7
270
600
726
596
412
1773
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
2.0 [0.59, 6.81]
1.05 [0.62, 1.78]
0.74 [0.45, 1.21]
2.88 [1.43, 5.77]
1.66 [0.86, 3.21]
1.01 [0.81, 1.26]
1
2
3
1
1
1
5
1
3
1
5
2
2
1
8
1
1
3
2
1
10
270
431
726
346
133
133
1342
270
726
346
1109
168
529
412
2040
270
36
726
596
412
2305
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.82 [0.49, 1.37]
1.42 [0.97, 2.09]
0.94 [0.66, 1.32]
0.86 [0.55, 1.34]
5.41 [0.61, 47.62]
5.41 [0.61, 47.62]
0.25 [0.15, 0.44]
0.13 [0.04, 0.44]
0.32 [0.17, 0.62]
0.21 [0.04, 0.97]
1.20 [0.79, 1.82]
2.14 [0.81, 5.66]
1.07 [0.59, 1.95]
1.01 [0.48, 2.12]
0.57 [0.41, 0.80]
0.47 [0.14, 1.60]
1.0 [0.06, 17.33]
0.89 [0.55, 1.46]
0.37 [0.21, 0.67]
0.34 [0.13, 0.87]
1.80 [1.37, 2.36]
1
3
3
2
1
11
270
301
726
596
412
2604
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.72 [0.81, 3.68]
3.68 [1.52, 8.91]
1.73 [0.81, 3.70]
1.53 [0.92, 2.55]
1.48 [0.77, 2.85]
0.33 [0.26, 0.43]
1
4
3
2
1
11
1
4
3
2
1
4
3
1
270
600
726
596
412
2604
270
600
726
596
412
576
301
275
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.45 [0.22, 0.90]
0.34 [0.14, 0.81]
0.27 [0.16, 0.44]
0.27 [0.16, 0.48]
0.29 [0.16, 0.53]
4.23 [2.93, 6.11]
3.83 [1.49, 9.82]
5.23 [2.15, 12.76]
3.92 [1.19, 12.92]
6.67 [3.30, 13.49]
2.51 [0.87, 7.26]
0.35 [0.10, 1.18]
0.42 [0.11, 1.62]
0.14 [0.01, 2.67]
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
69
18 Sexual dysfunction
18.1 vs Fluoxetine
18.2 vs Paroxetine
18.3 vs Sertraline
19 Anxiety/Agitation
19.1 vs Paroxetine
19.2 vs Sertraline
19.3 vs Fluvoxamine
20 Dizziness/Vertigo/Faintness
20.1 vs Citalolpram
20.2 vs Fluoxetine
20.3 vs Paroxetine
20.4 vs Sertraline
20.5 vs Fluvoxamine
21 Fatigue/Tiredness/Asthenia
21.1 vs Citalolpram
21.2 vs Fluoxetine
21.3 vs Paroxetine
21.4 vs Sertraline
21.5 vs Fluvoxamine
22 Headache
22.1 vs Citalolpram
22.2 vs Fluoxetine
22.3 vs Paroxetine
22.4 vs Sertraline
22.5 vs Fluvoxamine
23 Tremor
23.1 vs Fluoxetine
23.2 vs Paroxetine
24 Sleep disturbance
24.1 vs Fluoxetine
24.2 vs Paroxetine
24.3 vs Sertraline
25 Sleepiness/Drowsiness/
Somnolence
25.1 vs Citalolpram
25.2 vs Fluoxetine
25.3 vs Paroxetine
25.4 vs Sertraline
25.5 vs Fluvoxamine
26 Suicide attempt
26.1 vs Sertraline
27 Subgroup analysis: Response at
2 weeks: Treatment settings:
Outpatients in primary care
27.1 vs Paroxetine
28 Subgroup analysis: Response
at end of the acute-phase
treatment: Treatment settings:
Outpatients in primary care
28.1 vs Paroxetine
4
1
1
2
4
2
1
1
10
1
3
3
2
1
8
1
1
3
2
1
11
1
4
3
2
1
5
3
2
5
1
2
2
11
907
36
275
596
1134
472
250
412
2568
270
564
726
596
412
2137
270
133
726
596
412
2604
270
600
726
596
412
996
467
529
1346
299
451
596
2604
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.31 [0.13, 0.74]
0.15 [0.02, 1.47]
0.19 [0.06, 0.59]
0.43 [0.10, 1.82]
1.46 [0.59, 3.65]
0.71 [0.32, 1.60]
1.65 [0.69, 3.98]
5.76 [1.65, 20.07]
1.04 [0.77, 1.41]
2.03 [0.74, 5.58]
0.92 [0.54, 1.56]
0.84 [0.47, 1.50]
1.16 [0.36, 3.70]
1.31 [0.69, 2.48]
1.53 [1.08, 2.15]
0.91 [0.44, 1.84]
1.38 [0.30, 6.40]
1.71 [0.94, 3.11]
2.31 [1.32, 4.04]
0.94 [0.44, 2.00]
0.69 [0.56, 0.86]
0.63 [0.30, 1.33]
0.86 [0.54, 1.36]
0.57 [0.36, 0.89]
0.67 [0.44, 1.01]
0.84 [0.46, 1.53]
0.34 [0.18, 0.66]
0.42 [0.17, 1.07]
0.27 [0.11, 0.70]
0.52 [0.31, 0.86]
0.53 [0.21, 1.38]
0.68 [0.25, 1.85]
0.37 [0.16, 0.85]
1.81 [1.39, 2.37]
1
4
3
2
1
1
1
1
270
600
726
596
412
346
346
197
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.36 [0.53, 3.51]
1.59 [0.97, 2.61]
1.24 [0.84, 1.83]
3.07 [1.89, 4.99]
2.34 [1.45, 3.77]
4.89 [0.23, 102.51]
4.89 [0.23, 102.51]
4.38 [1.69, 11.35]
1
1
197
197
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
4.38 [1.69, 11.35]
1.17 [0.66, 2.10]
1
197
Odds Ratio (M-H, Random, 95% CI)
1.17 [0.66, 2.10]
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
70
29 Sensitivity analysis: Response
at 2 weeks: Studies without
imputation
29.1 vs Citalolpram
29.2 vs Fluoxetine
29.3 vs Paroxetine
29.4 vs Sertraline
29.5 vs Fluvoxamine
30 Sensitivity analysis: Response
at end of the acute-phase
treatment: Studies without
imputation
30.1 vs Citalolpram
30.2 vs Fluoxetine
30.3 vs Paroxetine
30.4 vs Sertraline
30.5 vs Fluvoxamine
31 Secondary outcome (SKEWED
DATA: depression severity) at
2 weeks
32 Secondary outcome (SKEWED
DATA: depression severity)
at end of the acute-phase
treatment
11
2604
Odds Ratio (M-H, Random, 95% CI)
1.58 [1.31, 1.90]
1
4
3
2
1
11
270
600
726
596
412
2604
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
2.01 [0.93, 4.35]
1.27 [0.86, 1.88]
2.39 [1.42, 4.02]
1.45 [1.04, 2.02]
1.38 [0.90, 2.13]
1.17 [1.00, 1.38]
1
4
3
2
1
270
600
726
596
412
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Other data
0.76 [0.38, 1.52]
1.46 [1.04, 2.04]
1.27 [0.94, 1.70]
0.97 [0.70, 1.35]
1.14 [0.76, 1.70]
No numeric data
Other data
No numeric data
Comparison 3. Mirtazapine versus SNRIs
Outcome or subgroup title
1 Primary outcome (response) at 2
weeks
1.1 vs Venlafaxine
2 Primary outcome (response)
at end of the acute-phase
treatment
2.1 vs Venlafaxine
3 Secondary outcome (remission)
at 2 weeks
3.1 vs Venlafaxine
4 Secondary outcome (remission)
at end of the acute-phase
treatment
4.1 vs Venlafaxine
5 Secondary outcome (withdrawal
due to any reason)
5.1 vs Venlafaxine
6 Secondary outcome (withdrawal
due to adverse events)
No. of
studies
No. of
participants
2
415
Odds Ratio (M-H, Random, 95% CI)
2.29 [1.45, 3.59]
2
2
415
415
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
2.29 [1.45, 3.59]
1.53 [1.03, 2.25]
2
2
415
415
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.53 [1.03, 2.25]
2.34 [1.07, 5.13]
2
2
415
415
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
2.34 [1.07, 5.13]
1.55 [0.98, 2.47]
2
2
415
415
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.55 [0.98, 2.47]
0.65 [0.43, 0.99]
2
2
415
415
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.65 [0.43, 0.99]
0.55 [0.24, 1.24]
Statistical method
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Effect size
71
6.1 vs Venlafaxine
7 Secondary outcome (having
some adverse events)
7.1 vs Venlafaxine
8 Hypotension/Bradycardia
8.1 vs Venlafaxine
9 Sweating
9.1 vs Venlafaxine
10 Constipation
10.1 vs Venlafaxine
11 Dry mouth/Decreased
salivation
11.1 vs Venlafaxine
12 Nausea/Vomiting/Gastric
distress
12.1 vs Venlafaxine
13 Anxiety/Agitation
13.1 vs Venlafaxine
14 Fatigue/Tiredness/Asthenia
14.1 vs Venlafaxine
15 Headache
15.1 vs Venlafaxine
16 Sleep disturbance
16.1 vs Venlafaxine
17 Sleepiness/Drowsiness/
Somnolence
17.1 vs Venlafaxine
18 Completed suicide
18.1 vs Venlafaxine
2
1
415
157
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.55 [0.24, 1.24]
1.51 [0.76, 3.00]
1
1
1
1
1
1
1
2
157
157
157
157
157
157
157
415
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.51 [0.76, 3.00]
0.19 [0.02, 1.68]
0.19 [0.02, 1.68]
0.03 [0.00, 0.45]
0.03 [0.00, 0.45]
0.22 [0.06, 0.83]
0.22 [0.06, 0.83]
8.61 [0.35, 211.85]
2
2
415
415
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
8.61 [0.35, 211.85]
0.11 [0.00, 9.34]
2
1
1
1
1
2
2
1
1
1
415
157
157
258
258
415
415
258
258
157
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.11 [0.00, 9.34]
1.01 [0.24, 4.20]
1.01 [0.24, 4.20]
2.43 [1.30, 4.55]
2.43 [1.30, 4.55]
0.95 [0.53, 1.72]
0.95 [0.53, 1.72]
0.02 [0.00, 0.41]
0.02 [0.00, 0.41]
1.56 [0.42, 5.77]
1
1
1
157
157
157
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.56 [0.42, 5.77]
0.33 [0.01, 8.31]
0.33 [0.01, 8.31]
Comparison 4. Mirtazapine versus heterocyclic antidepressants
Outcome or subgroup title
1 Primary outcome (response) at 2
weeks
1.1 vs Trazodone
2 Primary outcome (response)
at end of the acute-phase
treatment
2.1 vs Trazodone
3 Secondary outcome (remission)
at 2 weeks
3.1 vs Trazodone
4 Secondary outcome (remission)
at end of the acute-phase
treatment
4.1 vs Trazodone
No. of
studies
No. of
participants
2
300
Odds Ratio (M-H, Random, 95% CI)
1.14 [0.64, 2.04]
2
2
300
300
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.14 [0.64, 2.04]
1.50 [0.95, 2.37]
2
2
300
300
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.50 [0.95, 2.37]
1.0 [0.36, 2.80]
2
2
300
300
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.0 [0.36, 2.80]
1.38 [0.76, 2.52]
2
300
Odds Ratio (M-H, Random, 95% CI)
1.38 [0.76, 2.52]
Statistical method
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Effect size
72
5 Secondary outcome (withdrawal
due to any reason)
5.1 vs Trazodone
6 Secondary outcome (withdrawal
due to adverse events)
6.1 vs Trazodone
7 Hypertension/Tachycardia
7.1 vs Trazodone
8 Hypotension/Bradycardia
8.1 vs Trazodone
9 Constipation
9.1 vs Trazodone
10 Dry mouth/Decreased
salivation
10.1 vs Trazodone
11 Nausea/Vomiting/Gastric
distress
11.1 vs Trazodone
12 Weight gain/Increased appetite
12.1 vs Trazodone
13 Weight loss/Anorexia
13.1 vs Trazodone
14 Anxiety/Agitation
14.1 vs Trazodone
15 Dizziness/Vertigo/Faintness
15.1 vs Trazodone
16 Headache
16.1 vs Trazodone
17 Sleep disturbance
17.1 vs Trazodone
18 Sleepiness/Drowsiness/
Somnolence
18.1 vs Trazodone
19 Completed suicide
19.1 vs Trazodone
20 Suicide attempt
20.1 vs Trazodone
2
300
Odds Ratio (M-H, Random, 95% CI)
0.90 [0.47, 1.72]
2
2
300
300
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.90 [0.47, 1.72]
0.61 [0.25, 1.51]
2
1
1
2
2
1
1
2
300
100
100
300
300
100
100
300
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.61 [0.25, 1.51]
0.31 [0.06, 1.59]
0.31 [0.06, 1.59]
0.17 [0.03, 1.00]
0.17 [0.03, 1.00]
0.70 [0.26, 1.83]
0.70 [0.26, 1.83]
0.39 [0.11, 1.37]
2
1
300
100
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.39 [0.11, 1.37]
0.68 [0.20, 2.32]
1
1
1
1
1
2
2
2
2
1
1
1
1
2
100
100
100
100
100
300
300
300
300
100
100
200
200
300
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.68 [0.20, 2.32]
4.95 [1.30, 18.81]
4.95 [1.30, 18.81]
0.33 [0.01, 8.21]
0.33 [0.01, 8.21]
0.62 [0.19, 1.96]
0.62 [0.19, 1.96]
0.64 [0.30, 1.39]
0.64 [0.30, 1.39]
0.65 [0.23, 1.87]
0.65 [0.23, 1.87]
0.42 [0.13, 1.42]
0.42 [0.13, 1.42]
0.62 [0.29, 1.36]
2
1
1
1
1
300
200
200
200
200
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.62 [0.29, 1.36]
3.03 [0.12, 75.28]
3.03 [0.12, 75.28]
2.02 [0.18, 22.65]
2.02 [0.18, 22.65]
Comparison 5. Mirtazapine versus newer antidepressants
Outcome or subgroup title
1 Primary outcome (response) at 2
weeks
1.1 vs Reboxetine
2 Primary outcome (response)
at end of the acute-phase
treatment
2.1 vs Reboxetine
No. of
studies
No. of
participants
1
40
Odds Ratio (M-H, Random, 95% CI)
1.0 [0.18, 5.67]
1
1
40
40
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.0 [0.18, 5.67]
1.0 [0.27, 3.67]
1
40
Odds Ratio (M-H, Random, 95% CI)
1.0 [0.27, 3.67]
Statistical method
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Effect size
73
3 Secondary outcome (remission)
at 2 weeks
3.1 vs Reboxetine
4 Secondary outcome (remission)
at end of the acute-phase
treatment
4.1 vs Reboxetine
5 Secondary outcome (depression
severity) at 2 weeks
5.1 vs Reboxetine
6 Secondary outcome (withdrawal
due to any reason)
6.1 vs Reboxetine
7 Secondary outcome (withdrawal
due to adverse events)
7.1 vs Reboxetine
8 Secondary outcome (SKEWED
DATA: depression severity)
at end of the acute-phase
treatment
1
40
Odds Ratio (M-H, Random, 95% CI)
1.0 [0.06, 17.18]
1
1
40
40
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
1.0 [0.06, 17.18]
1.26 [0.33, 4.73]
1
1
40
40
Odds Ratio (M-H, Random, 95% CI)
Std. Mean Difference (IV, Random, 95% CI)
1.26 [0.33, 4.73]
-0.37 [-1.00, 0.25]
1
2
40
80
Std. Mean Difference (IV, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
-0.37 [-1.00, 0.25]
0.0 [0.0, 0.0]
2
2
80
80
Odds Ratio (M-H, Random, 95% CI)
Odds Ratio (M-H, Random, 95% CI)
0.0 [0.0, 0.0]
0.0 [0.0, 0.0]
2
80
Odds Ratio (M-H, Random, 95% CI)
Other data
0.0 [0.0, 0.0]
No numeric data
Comparison 6. Funnel plot analysis: primary outcome (response) at end of the acute-phase treatment
Outcome or subgroup title
1 vs all compounds
1.1 vs Amitriptyline
1.2 vs Clomipramine
1.3 vs Doxepin
1.4 vs Nortriptyline
1.5 vs Citalolpram
1.6 vs Fluoxetine
1.7 vs Paroxetine
1.8 vs Sertraline
1.9 vs Fluvoxamine
1.10 vs Venlafaxine
1.11 vs Trazodone
1.12 vs Reboxetine
No. of
studies
No. of
participants
26
6
1
1
1
1
5
3
2
1
2
2
1
4882
929
174
163
235
270
622
726
596
412
415
300
40
Statistical method
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Risk Ratio (M-H, Fixed, 99% CI)
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Effect size
1.05 [0.99, 1.12]
0.95 [0.82, 1.11]
0.97 [0.74, 1.26]
0.95 [0.71, 1.26]
0.94 [0.59, 1.49]
0.96 [0.85, 1.09]
1.18 [1.00, 1.39]
1.13 [0.93, 1.38]
0.99 [0.83, 1.17]
1.05 [0.86, 1.28]
1.24 [0.96, 1.60]
1.21 [0.91, 1.61]
1.0 [0.55, 1.82]
74
Analysis 1.1. Comparison 1 Mirtazapine versus TCAs, Outcome 1 Primary outcome (response) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 1 Primary outcome (response) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
7/50
8/50
6.5 %
0.85 [ 0.28, 2.57 ]
Hoyberg 1996
10/56
12/59
9.1 %
0.85 [ 0.34, 2.16 ]
Mullin 1996
18/79
23/77
15.3 %
0.69 [ 0.34, 1.42 ]
Smith 1990
18/50
20/50
12.1 %
0.84 [ 0.38, 1.89 ]
Zivkov 1995
16/125
21/126
15.9 %
0.73 [ 0.36, 1.48 ]
360
362
58.9 %
0.77 [ 0.54, 1.12 ]
1 vs Amitriptyline
Subtotal (95% CI)
Total events: 69 (Mirtazapine), 84 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.23, df = 4 (P = 0.99); I2 =0.0%
Test for overall effect: Z = 1.37 (P = 0.17)
2 vs Clomipramine
Richou 1995
23/87
25/87
17.8 %
0.89 [ 0.46, 1.73 ]
87
87
17.8 %
0.89 [ 0.46, 1.73 ]
30/83
27/80
19.0 %
1.11 [ 0.58, 2.12 ]
83
80
19.0 %
1.11 [ 0.58, 2.12 ]
4/114
5/121
4.4 %
0.84 [ 0.22, 3.22 ]
114
121
4.4 %
0.84 [ 0.22, 3.22 ]
644
650
100.0 %
0.85 [ 0.64, 1.13 ]
Subtotal (95% CI)
Total events: 23 (Mirtazapine), 25 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.34 (P = 0.73)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 30 (Mirtazapine), 27 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.32 (P = 0.75)
4 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
Total events: 4 (Mirtazapine), 5 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.25 (P = 0.80)
Total (95% CI)
Total events: 126 (Mirtazapine), 141 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.16, df = 7 (P = 0.99); I2 =0.0%
Test for overall effect: Z = 1.11 (P = 0.27)
Test for subgroup differences: Chi2 = 0.93, df = 3 (P = 0.82), I2 =0.0%
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
75
Analysis 1.2. Comparison 1 Mirtazapine versus TCAs, Outcome 2 Primary outcome (response) at end of
the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 2 Primary outcome (response) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
31/50
24/50
6.9 %
1.77 [ 0.80, 3.92 ]
Hoyberg 1996
25/56
34/59
8.0 %
0.59 [ 0.28, 1.24 ]
Mullin 1996
38/79
41/77
11.1 %
0.81 [ 0.43, 1.53 ]
53/103
62/104
14.5 %
0.72 [ 0.41, 1.24 ]
Smith 1990
25/50
26/50
7.1 %
0.92 [ 0.42, 2.02 ]
Zivkov 1995
81/125
80/126
16.4 %
1.06 [ 0.63, 1.77 ]
463
466
64.1 %
0.90 [ 0.69, 1.17 ]
1 vs Amitriptyline
Organon 85146
Subtotal (95% CI)
Total events: 253 (Mirtazapine), 267 (Others)
Heterogeneity: Tau2 = 0.00; Chi2 = 5.12, df = 5 (P = 0.40); I2 =2%
Test for overall effect: Z = 0.80 (P = 0.42)
2 vs Clomipramine
Richou 1995
59/87
61/87
10.6 %
0.90 [ 0.47, 1.71 ]
87
87
10.6 %
0.90 [ 0.47, 1.71 ]
54/83
55/80
10.3 %
0.85 [ 0.44, 1.63 ]
83
80
10.3 %
0.85 [ 0.44, 1.63 ]
38/114
43/121
15.1 %
0.91 [ 0.53, 1.55 ]
114
121
15.1 %
0.91 [ 0.53, 1.55 ]
Subtotal (95% CI)
Total events: 59 (Mirtazapine), 61 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.33 (P = 0.74)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 54 (Mirtazapine), 55 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.50 (P = 0.62)
4 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
76
(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
747
754
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Total events: 38 (Mirtazapine), 43 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.36 (P = 0.72)
Total (95% CI)
100.0 %
0.89 [ 0.72, 1.10 ]
Total events: 404 (Mirtazapine), 426 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 5.15, df = 8 (P = 0.74); I2 =0.0%
Test for overall effect: Z = 1.06 (P = 0.29)
Test for subgroup differences: Chi2 = 0.03, df = 3 (P = 1.00), I2 =0.0%
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 1.3. Comparison 1 Mirtazapine versus TCAs, Outcome 3 Secondary outcome (remission) at 2
weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 3 Secondary outcome (remission) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
1/50
1/50
2.5 %
1.00 [ 0.06, 16.44 ]
Hoyberg 1996
3/56
5/59
8.9 %
0.61 [ 0.14, 2.69 ]
Mullin 1996
5/79
5/77
11.9 %
0.97 [ 0.27, 3.50 ]
Smith 1990
6/50
8/50
15.1 %
0.72 [ 0.23, 2.24 ]
Zivkov 1995
2/125
6/126
7.5 %
0.33 [ 0.06, 1.64 ]
360
362
45.9 %
0.67 [ 0.35, 1.29 ]
1 vs Amitriptyline
Subtotal (95% CI)
Total events: 17 (Mirtazapine), 25 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.20, df = 4 (P = 0.88); I2 =0.0%
Test for overall effect: Z = 1.19 (P = 0.24)
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
77
(. . .
Study or subgroup
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Mirtazapine
Others
n/N
n/N
9/87
10/87
21.5 %
0.89 [ 0.34, 2.31 ]
87
87
21.5 %
0.89 [ 0.34, 2.31 ]
14/83
11/80
26.6 %
1.27 [ 0.54, 3.00 ]
83
80
26.6 %
1.27 [ 0.54, 3.00 ]
2/114
3/121
6.0 %
0.70 [ 0.12, 4.28 ]
114
121
6.0 %
0.70 [ 0.12, 4.28 ]
644
650
100.0 %
0.85 [ 0.55, 1.32 ]
2 vs Clomipramine
Richou 1995
Subtotal (95% CI)
Total events: 9 (Mirtazapine), 10 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.24 (P = 0.81)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 14 (Mirtazapine), 11 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.55 (P = 0.58)
4 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
Total events: 2 (Mirtazapine), 3 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.38 (P = 0.70)
Total (95% CI)
Total events: 42 (Mirtazapine), 49 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.59, df = 7 (P = 0.92); I2 =0.0%
Test for overall effect: Z = 0.73 (P = 0.47)
Test for subgroup differences: Chi2 = 1.39, df = 3 (P = 0.71), I2 =0.0%
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
78
Analysis 1.4. Comparison 1 Mirtazapine versus TCAs, Outcome 4 Secondary outcome (remission) at end
of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 4 Secondary outcome (remission) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
8/50
7/50
4.2 %
1.17 [ 0.39, 3.51 ]
Hoyberg 1996
14/56
19/59
7.7 %
0.70 [ 0.31, 1.59 ]
Mullin 1996
18/79
21/77
9.7 %
0.79 [ 0.38, 1.63 ]
33/103
35/104
15.3 %
0.93 [ 0.52, 1.66 ]
Smith 1990
10/50
13/50
5.8 %
0.71 [ 0.28, 1.82 ]
Zivkov 1995
36/125
38/126
17.4 %
0.94 [ 0.54, 1.61 ]
463
466
60.3 %
0.87 [ 0.65, 1.16 ]
1 vs Amitriptyline
Organon 85146
Subtotal (95% CI)
Total events: 119 (Mirtazapine), 133 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.92, df = 5 (P = 0.97); I2 =0.0%
Test for overall effect: Z = 0.96 (P = 0.34)
2 vs Clomipramine
Richou 1995
26/87
31/87
12.7 %
0.77 [ 0.41, 1.45 ]
87
87
12.7 %
0.77 [ 0.41, 1.45 ]
35/83
35/80
13.4 %
0.94 [ 0.50, 1.74 ]
83
80
13.4 %
0.94 [ 0.50, 1.74 ]
24/114
29/121
13.6 %
0.85 [ 0.46, 1.56 ]
114
121
13.6 %
0.85 [ 0.46, 1.56 ]
754
100.0 %
0.86 [ 0.69, 1.08 ]
Subtotal (95% CI)
Total events: 26 (Mirtazapine), 31 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.81 (P = 0.42)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 35 (Mirtazapine), 35 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.20 (P = 0.84)
4 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
Total events: 24 (Mirtazapine), 29 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.53 (P = 0.59)
Total (95% CI)
747
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
79
(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Total events: 204 (Mirtazapine), 228 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.11, df = 8 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 1.31 (P = 0.19)
Test for subgroup differences: Chi2 = 0.20, df = 3 (P = 0.98), I2 =0.0%
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Analysis 1.5. Comparison 1 Mirtazapine versus TCAs, Outcome 5 Secondary outcome (depression
severity) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 5 Secondary outcome (depression severity) at 2 weeks
Study or subgroup
Mirtazapine
Std.
Mean
Difference
Control
Weight
IV,Random,95% CI
Std.
Mean
Difference
N
Mean(SD)
N
Mean(SD)
IV,Random,95% CI
Mullin 1996
69
15.6 (5.9)
68
14.3 (5.1)
38.1 %
0.23 [ -0.10, 0.57 ]
Zivkov 1995
113
20.9 (6.4)
111
20.8 (7.8)
61.9 %
0.01 [ -0.25, 0.28 ]
100.0 %
0.10 [ -0.11, 0.31 ]
1 vs Amitritpyline
Total (95% CI)
182
179
Heterogeneity: Tau2 = 0.00; Chi2 = 1.03, df = 1 (P = 0.31); I2 =3%
Test for overall effect: Z = 0.92 (P = 0.36)
Test for subgroup differences: Not applicable
-4
-2
Favours mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
0
2
4
Favours control
80
Analysis 1.6. Comparison 1 Mirtazapine versus TCAs, Outcome 6 Secondary outcome (depression
severity) at end of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 6 Secondary outcome (depression severity) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Std.
Mean
Difference
Control
N
Mean(SD)
N
Mean(SD)
71
-17.3 (7.5)
73
-18.2 (7.5)
Weight
IV,Random,95% CI
Std.
Mean
Difference
IV,Random,95% CI
1 vs Amitritpyline
Organon 85146
Total (95% CI)
71
73
100.0 %
0.12 [ -0.21, 0.45 ]
100.0 %
0.12 [ -0.21, 0.45 ]
Heterogeneity: not applicable
Test for overall effect: Z = 0.72 (P = 0.47)
Test for subgroup differences: Not applicable
-4
-2
0
Favours mirtazapine
2
4
Favours control
Analysis 1.7. Comparison 1 Mirtazapine versus TCAs, Outcome 7 Secondary outcome (Social adjustment)
at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 7 Secondary outcome (Social adjustment) at 2 weeks
Study or subgroup
Mirtazapine
Mean
Difference
Control
N
Mean(SD)
N
Mean(SD)
70
-56.8 (11.5)
68
-58.4 (9.9)
Weight
IV,Random,95% CI
Mean
Difference
IV,Random,95% CI
1 vs Amitriptyline
Mullin 1996
Total (95% CI)
70
68
100.0 %
1.60 [ -1.98, 5.18 ]
100.0 %
1.60 [ -1.98, 5.18 ]
Heterogeneity: not applicable
Test for overall effect: Z = 0.88 (P = 0.38)
Test for subgroup differences: Not applicable
-100
-50
Favours experimental
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
0
50
100
Favours control
81
Analysis 1.8. Comparison 1 Mirtazapine versus TCAs, Outcome 8 Secondary outcome (Social adjustment)
at end of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 8 Secondary outcome (Social adjustment) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Std.
Mean
Difference
Control
N
Mean(SD)
N
Mean(SD)
59
-69.5 (15.1)
55
-69.9 (13.5)
Weight
IV,Random,95% CI
Std.
Mean
Difference
IV,Random,95% CI
1 vs Amitriptyline
Mullin 1996
Subtotal (95% CI)
59
25.9 %
0.03 [ -0.34, 0.40 ]
25.9 %
0.03 [ -0.34, 0.40 ]
37.0 %
0.12 [ -0.19, 0.43 ]
37.0 %
0.12 [ -0.19, 0.43 ]
37.1 %
-0.09 [ -0.39, 0.22 ]
80
37.1 %
-0.09 [ -0.39, 0.22 ]
216
100.0 %
0.02 [ -0.17, 0.21 ]
55
Heterogeneity: not applicable
Test for overall effect: Z = 0.15 (P = 0.88)
2 vs Clomipramine
Richou 1995
Subtotal (95% CI)
82
-74.1 (12.6)
82
81
-75.7 (14.3)
81
Heterogeneity: not applicable
Test for overall effect: Z = 0.75 (P = 0.45)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
83
83
-67.9 (14.3)
80
-66.7 (13.5)
Heterogeneity: not applicable
Test for overall effect: Z = 0.55 (P = 0.58)
Total (95% CI)
224
Heterogeneity: Tau2 = 0.0; Chi2 = 0.85, df = 2 (P = 0.65); I2 =0.0%
Test for overall effect: Z = 0.20 (P = 0.84)
Test for subgroup differences: Chi2 = 0.85, df = 2 (P = 0.65), I2 =0.0%
-100
-50
Favours experimental
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
0
50
100
Favours control
82
Analysis 1.9. Comparison 1 Mirtazapine versus TCAs, Outcome 9 Secondary outcome (withdrawal due to
any reason).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 9 Secondary outcome (withdrawal due to any reason)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
9/50
10/50
7.7 %
0.88 [ 0.32, 2.39 ]
Hoyberg 1996
13/56
11/59
9.5 %
1.32 [ 0.54, 3.25 ]
Mullin 1996
15/79
18/77
13.0 %
0.77 [ 0.36, 1.66 ]
Organon 85146
26/103
27/104
19.9 %
0.96 [ 0.52, 1.80 ]
Zivkov 1995
24/125
29/126
20.9 %
0.79 [ 0.43, 1.46 ]
413
416
71.0 %
0.90 [ 0.65, 1.25 ]
1 vs Amitriptyline
Subtotal (95% CI)
Total events: 87 (Mirtazapine), 95 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.06, df = 4 (P = 0.90); I2 =0.0%
Test for overall effect: Z = 0.61 (P = 0.54)
2 vs Clomipramine
Richou 1995
24/87
28/87
18.3 %
0.80 [ 0.42, 1.54 ]
87
87
18.3 %
0.80 [ 0.42, 1.54 ]
10/83
17/80
10.7 %
0.51 [ 0.22, 1.19 ]
83
80
10.7 %
0.51 [ 0.22, 1.19 ]
583
583
100.0 %
0.83 [ 0.63, 1.10 ]
Subtotal (95% CI)
Total events: 24 (Mirtazapine), 28 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.66 (P = 0.51)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 10 (Mirtazapine), 17 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.56 (P = 0.12)
Total (95% CI)
Total events: 121 (Mirtazapine), 140 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.59, df = 6 (P = 0.86); I2 =0.0%
Test for overall effect: Z = 1.31 (P = 0.19)
Test for subgroup differences: Chi2 = 1.53, df = 2 (P = 0.46), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
83
Analysis 1.10. Comparison 1 Mirtazapine versus TCAs, Outcome 10 Secondary outcome (withdrawal due
to adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 10 Secondary outcome (withdrawal due to adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
3/50
5/50
9.5 %
0.57 [ 0.13, 2.55 ]
Hoyberg 1996
1/56
1/59
2.7 %
1.05 [ 0.06, 17.28 ]
Mullin 1996
7/79
13/77
22.0 %
0.48 [ 0.18, 1.27 ]
5/103
6/104
14.1 %
0.83 [ 0.25, 2.82 ]
Smith 1990
7/50
10/50
18.8 %
0.65 [ 0.23, 1.87 ]
Zivkov 1995
1/125
3/126
4.1 %
0.33 [ 0.03, 3.22 ]
463
466
71.2 %
0.60 [ 0.35, 1.03 ]
1 vs Amitriptyline
Organon 85146
Subtotal (95% CI)
Total events: 24 (Mirtazapine), 38 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.93, df = 5 (P = 0.97); I2 =0.0%
Test for overall effect: Z = 1.85 (P = 0.065)
2 vs Clomipramine
9/87
8/87
20.9 %
1.14 [ 0.42, 3.10 ]
87
87
20.9 %
1.14 [ 0.42, 3.10 ]
2/83
6/80
7.9 %
0.30 [ 0.06, 1.56 ]
83
80
7.9 %
0.30 [ 0.06, 1.56 ]
633
633
100.0 %
0.65 [ 0.41, 1.03 ]
Richou 1995
Subtotal (95% CI)
Total events: 9 (Mirtazapine), 8 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.26 (P = 0.80)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 2 (Mirtazapine), 6 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.43 (P = 0.15)
Total (95% CI)
Total events: 35 (Mirtazapine), 52 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 3.05, df = 7 (P = 0.88); I2 =0.0%
Test for overall effect: Z = 1.84 (P = 0.065)
Test for subgroup differences: Chi2 = 2.12, df = 2 (P = 0.35), I2 =6%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
84
Analysis 1.11. Comparison 1 Mirtazapine versus TCAs, Outcome 11 Secondary outcome (having some
adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 11 Secondary outcome (having some adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
99/103
101/104
19.9 %
0.74 [ 0.16, 3.37 ]
103
104
19.9 %
0.74 [ 0.16, 3.37 ]
100/114
104/121
80.1 %
1.17 [ 0.55, 2.49 ]
114
121
80.1 %
1.17 [ 0.55, 2.49 ]
225
100.0 %
1.06 [ 0.54, 2.10 ]
1 vs Amitriptyline
Organon 85146
Subtotal (95% CI)
Total events: 99 (Mirtazapine), 101 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.40 (P = 0.69)
2 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
Total events: 100 (Mirtazapine), 104 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.40 (P = 0.69)
Total (95% CI)
217
Total events: 199 (Mirtazapine), 205 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.28, df = 1 (P = 0.59); I2 =0.0%
Test for overall effect: Z = 0.18 (P = 0.86)
Test for subgroup differences: Chi2 = 0.28, df = 1 (P = 0.59), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
85
Analysis 1.12. Comparison 1 Mirtazapine versus TCAs, Outcome 12 Hypertension/Tachycardia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 12 Hypertension/Tachycardia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
0/50
4/50
4.2 %
0.10 [ 0.01, 1.95 ]
Hoyberg 1996
0/56
4/59
4.2 %
0.11 [ 0.01, 2.08 ]
15/103
26/104
74.0 %
0.51 [ 0.25, 1.03 ]
3/50
6/50
17.6 %
0.47 [ 0.11, 1.99 ]
259
263
100.0 %
0.44 [ 0.24, 0.81 ]
1 vs Amitriptyline
Organon 85146
Smith 1990
Total (95% CI)
Total events: 18 (Mirtazapine), 40 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.05, df = 3 (P = 0.56); I2 =0.0%
Test for overall effect: Z = 2.65 (P = 0.0080)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
86
Analysis 1.13. Comparison 1 Mirtazapine versus TCAs, Outcome 13 Hypotension/Bradycardia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 13 Hypotension/Bradycardia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Hoyberg 1996
2/56
2/59
41.3 %
1.06 [ 0.14, 7.76 ]
Smith 1990
2/50
7/50
58.7 %
0.26 [ 0.05, 1.30 ]
106
109
100.0 %
0.46 [ 0.12, 1.81 ]
1 vs Amitriptyline
Total (95% CI)
Total events: 4 (Mirtazapine), 9 (Others)
Heterogeneity: Tau2 = 0.15; Chi2 = 1.17, df = 1 (P = 0.28); I2 =15%
Test for overall effect: Z = 1.11 (P = 0.27)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
87
Analysis 1.14. Comparison 1 Mirtazapine versus TCAs, Outcome 14 Sweating.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 14 Sweating
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
22/103
26/104
70.1 %
0.81 [ 0.43, 1.56 ]
0/125
5/126
29.9 %
0.09 [ 0.00, 1.61 ]
228
230
100.0 %
0.42 [ 0.05, 3.24 ]
1 vs Amitriptyline
Organon 85146
Zivkov 1995
Total (95% CI)
Total events: 22 (Mirtazapine), 31 (Others)
Heterogeneity: Tau2 = 1.44; Chi2 = 2.25, df = 1 (P = 0.13); I2 =56%
Test for overall effect: Z = 0.83 (P = 0.40)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
88
Analysis 1.15. Comparison 1 Mirtazapine versus TCAs, Outcome 15 Constipation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 15 Constipation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
4/50
12/50
11.8 %
0.28 [ 0.08, 0.92 ]
Hoyberg 1996
13/56
11/59
19.1 %
1.32 [ 0.54, 3.25 ]
1/79
5/77
4.0 %
0.18 [ 0.02, 1.62 ]
34/103
39/104
35.7 %
0.82 [ 0.46, 1.45 ]
4/125
4/126
9.0 %
1.01 [ 0.25, 4.12 ]
413
416
79.6 %
0.72 [ 0.40, 1.29 ]
1 vs Amitriptyline
Mullin 1996
Organon 85146
Zivkov 1995
Subtotal (95% CI)
Total events: 56 (Mirtazapine), 71 (Others)
Heterogeneity: Tau2 = 0.14; Chi2 = 6.02, df = 4 (P = 0.20); I2 =34%
Test for overall effect: Z = 1.12 (P = 0.26)
2 vs Clomipramine
Richou 1995
10/87
15/87
20.4 %
0.62 [ 0.26, 1.48 ]
87
87
20.4 %
0.62 [ 0.26, 1.48 ]
500
503
100.0 %
0.72 [ 0.46, 1.12 ]
Subtotal (95% CI)
Total events: 10 (Mirtazapine), 15 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.07 (P = 0.28)
Total (95% CI)
Total events: 66 (Mirtazapine), 86 (Others)
Heterogeneity: Tau2 = 0.06; Chi2 = 6.20, df = 5 (P = 0.29); I2 =19%
Test for overall effect: Z = 1.46 (P = 0.14)
Test for subgroup differences: Chi2 = 0.07, df = 1 (P = 0.79), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
89
Analysis 1.16. Comparison 1 Mirtazapine versus TCAs, Outcome 16 Dry mouth/Decreased salivation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 16 Dry mouth/Decreased salivation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
27/50
40/50
12.2 %
0.29 [ 0.12, 0.71 ]
Hoyberg 1996
21/56
26/59
12.7 %
0.76 [ 0.36, 1.61 ]
7/79
23/77
12.0 %
0.23 [ 0.09, 0.57 ]
47/103
34/104
13.4 %
1.73 [ 0.98, 3.04 ]
9/50
41/50
11.6 %
0.05 [ 0.02, 0.13 ]
16/125
34/126
13.1 %
0.40 [ 0.21, 0.77 ]
463
466
75.0 %
0.36 [ 0.14, 0.92 ]
1 vs Amitriptyline
Mullin 1996
Organon 85146
Smith 1990
Zivkov 1995
Subtotal (95% CI)
Total events: 127 (Mirtazapine), 198 (Others)
Heterogeneity: Tau2 = 1.20; Chi2 = 44.69, df = 5 (P<0.00001); I2 =89%
Test for overall effect: Z = 2.13 (P = 0.034)
2 vs Clomipramine
Richou 1995
17/87
20/87
12.8 %
0.81 [ 0.39, 1.69 ]
87
87
12.8 %
0.81 [ 0.39, 1.69 ]
20/83
8/80
12.2 %
2.86 [ 1.18, 6.94 ]
83
80
12.2 %
2.86 [ 1.18, 6.94 ]
633
633
100.0 %
0.52 [ 0.24, 1.14 ]
Subtotal (95% CI)
Total events: 17 (Mirtazapine), 20 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.56 (P = 0.58)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 20 (Mirtazapine), 8 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.32 (P = 0.020)
Total (95% CI)
Total events: 164 (Mirtazapine), 226 (Others)
Heterogeneity: Tau2 = 1.12; Chi2 = 58.07, df = 7 (P<0.00001); I2 =88%
Test for overall effect: Z = 1.64 (P = 0.10)
Test for subgroup differences: Chi2 = 10.17, df = 2 (P = 0.01), I2 =80%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
90
Analysis 1.17. Comparison 1 Mirtazapine versus TCAs, Outcome 17 Nausea/Vomiting/Gastric distress.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 17 Nausea/Vomiting/Gastric distress
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
2/50
10/50
25.5 %
0.17 [ 0.03, 0.81 ]
25/103
17/104
30.9 %
1.64 [ 0.82, 3.26 ]
1/50
10/50
21.9 %
0.08 [ 0.01, 0.67 ]
203
204
78.4 %
0.33 [ 0.04, 2.59 ]
1 vs Amitriptyline
Bremner 1995
Organon 85146
Smith 1990
Subtotal (95% CI)
Total events: 28 (Mirtazapine), 37 (Others)
Heterogeneity: Tau2 = 2.74; Chi2 = 12.91, df = 2 (P = 0.002); I2 =85%
Test for overall effect: Z = 1.05 (P = 0.29)
2 vs Clomipramine
Richou 1995
1/87
6/87
21.6 %
0.16 [ 0.02, 1.33 ]
87
87
21.6 %
0.16 [ 0.02, 1.33 ]
290
291
100.0 %
0.29 [ 0.05, 1.59 ]
Subtotal (95% CI)
Total events: 1 (Mirtazapine), 6 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.70 (P = 0.090)
Total (95% CI)
Total events: 29 (Mirtazapine), 43 (Others)
Heterogeneity: Tau2 = 2.36; Chi2 = 15.37, df = 3 (P = 0.002); I2 =80%
Test for overall effect: Z = 1.43 (P = 0.15)
Test for subgroup differences: Chi2 = 0.24, df = 1 (P = 0.62), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
91
Analysis 1.18. Comparison 1 Mirtazapine versus TCAs, Outcome 18 Weight gain/Increased appetite.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 18 Weight gain/Increased appetite
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
4/79
7/77
17.4 %
0.53 [ 0.15, 1.90 ]
38/103
40/104
53.3 %
0.94 [ 0.53, 1.64 ]
16/50
10/50
29.3 %
1.88 [ 0.76, 4.69 ]
232
231
100.0 %
1.04 [ 0.58, 1.86 ]
1 vs Amitriptyline
Mullin 1996
Organon 85146
Smith 1990
Total (95% CI)
Total events: 58 (Mirtazapine), 57 (Others)
Heterogeneity: Tau2 = 0.08; Chi2 = 2.82, df = 2 (P = 0.24); I2 =29%
Test for overall effect: Z = 0.14 (P = 0.89)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
92
Analysis 1.19. Comparison 1 Mirtazapine versus TCAs, Outcome 19 Sexual dysfunction.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 19 Sexual dysfunction
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
0/50
4/50
30.3 %
0.10 [ 0.01, 1.95 ]
3/125
4/126
69.7 %
0.75 [ 0.16, 3.42 ]
175
176
100.0 %
0.41 [ 0.06, 2.61 ]
1 vs Amitriptyline
Bremner 1995
Zivkov 1995
Total (95% CI)
Total events: 3 (Mirtazapine), 8 (Others)
Heterogeneity: Tau2 = 0.67; Chi2 = 1.47, df = 1 (P = 0.23); I2 =32%
Test for overall effect: Z = 0.94 (P = 0.34)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
93
Analysis 1.20. Comparison 1 Mirtazapine versus TCAs, Outcome 20 Anxiety/Agitation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 20 Anxiety/Agitation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
2/50
5/50
24.2 %
0.38 [ 0.07, 2.03 ]
24/103
22/104
75.8 %
1.13 [ 0.59, 2.18 ]
153
154
100.0 %
0.87 [ 0.34, 2.19 ]
1 vs Amitriptyline
Bremner 1995
Organon 85146
Total (95% CI)
Total events: 26 (Mirtazapine), 27 (Others)
Heterogeneity: Tau2 = 0.18; Chi2 = 1.43, df = 1 (P = 0.23); I2 =30%
Test for overall effect: Z = 0.30 (P = 0.76)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
94
Analysis 1.21. Comparison 1 Mirtazapine versus TCAs, Outcome 21 Dizziness/Vertigo/Faintness.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 21 Dizziness/Vertigo/Faintness
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
12/56
9/59
19.3 %
1.52 [ 0.58, 3.94 ]
1/79
5/77
5.5 %
0.18 [ 0.02, 1.62 ]
23/103
32/104
29.4 %
0.65 [ 0.35, 1.21 ]
Smith 1990
3/50
9/50
11.7 %
0.29 [ 0.07, 1.15 ]
Zivkov 1995
3/125
5/126
10.7 %
0.60 [ 0.14, 2.55 ]
413
416
76.6 %
0.64 [ 0.35, 1.17 ]
1 vs Amitriptyline
Hoyberg 1996
Mullin 1996
Organon 85146
Subtotal (95% CI)
Total events: 42 (Mirtazapine), 60 (Others)
Heterogeneity: Tau2 = 0.13; Chi2 = 5.64, df = 4 (P = 0.23); I2 =29%
Test for overall effect: Z = 1.44 (P = 0.15)
2 vs Clomipramine
Richou 1995
5/87
7/87
14.5 %
0.70 [ 0.21, 2.29 ]
87
87
14.5 %
0.70 [ 0.21, 2.29 ]
6/83
2/80
8.9 %
3.04 [ 0.59, 15.53 ]
83
80
8.9 %
3.04 [ 0.59, 15.53 ]
583
583
100.0 %
0.75 [ 0.43, 1.28 ]
Subtotal (95% CI)
Total events: 5 (Mirtazapine), 7 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.60 (P = 0.55)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 6 (Mirtazapine), 2 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.34 (P = 0.18)
Total (95% CI)
Total events: 53 (Mirtazapine), 69 (Others)
Heterogeneity: Tau2 = 0.16; Chi2 = 8.68, df = 6 (P = 0.19); I2 =31%
Test for overall effect: Z = 1.07 (P = 0.28)
Test for subgroup differences: Chi2 = 3.08, df = 2 (P = 0.21), I2 =35%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
95
Analysis 1.22. Comparison 1 Mirtazapine versus TCAs, Outcome 22 Fatigue/Tiredness/Asthenia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 22 Fatigue/Tiredness/Asthenia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
6/50
4/50
18.2 %
1.57 [ 0.41, 5.93 ]
Hoyberg 1996
9/56
5/59
23.9 %
2.07 [ 0.65, 6.60 ]
11/103
9/104
37.5 %
1.26 [ 0.50, 3.19 ]
4/125
7/126
20.5 %
0.56 [ 0.16, 1.97 ]
334
339
100.0 %
1.25 [ 0.71, 2.21 ]
1 vs Amitriptyline
Organon 85146
Zivkov 1995
Total (95% CI)
Total events: 30 (Mirtazapine), 25 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.40, df = 3 (P = 0.49); I2 =0.0%
Test for overall effect: Z = 0.78 (P = 0.44)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
96
Analysis 1.23. Comparison 1 Mirtazapine versus TCAs, Outcome 23 Headache.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 23 Headache
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
2/50
2/50
13.5 %
1.00 [ 0.14, 7.39 ]
Hoyberg 1996
4/56
4/59
21.0 %
1.06 [ 0.25, 4.45 ]
25/103
22/104
39.7 %
1.19 [ 0.62, 2.29 ]
4/50
14/50
25.7 %
0.22 [ 0.07, 0.74 ]
259
263
100.0 %
0.74 [ 0.31, 1.74 ]
1 vs Amitriptyline
Organon 85146
Smith 1990
Total (95% CI)
Total events: 35 (Mirtazapine), 42 (Others)
Heterogeneity: Tau2 = 0.37; Chi2 = 6.00, df = 3 (P = 0.11); I2 =50%
Test for overall effect: Z = 0.69 (P = 0.49)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
97
Analysis 1.24. Comparison 1 Mirtazapine versus TCAs, Outcome 24 Tremor.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 24 Tremor
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
1/50
3/50
4.2 %
0.32 [ 0.03, 3.18 ]
Hoyberg 1996
1/56
3/59
4.2 %
0.34 [ 0.03, 3.36 ]
Mullin 1996
1/79
4/77
4.5 %
0.23 [ 0.03, 2.14 ]
16/103
31/104
47.8 %
0.43 [ 0.22, 0.85 ]
Smith 1990
0/50
7/50
2.6 %
0.06 [ 0.00, 1.03 ]
Zivkov 1995
2/125
7/126
8.7 %
0.28 [ 0.06, 1.36 ]
463
466
72.0 %
0.36 [ 0.20, 0.62 ]
1 vs Amitriptyline
Organon 85146
Subtotal (95% CI)
Total events: 21 (Mirtazapine), 55 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.17, df = 5 (P = 0.82); I2 =0.0%
Test for overall effect: Z = 3.67 (P = 0.00024)
2 vs Clomipramine
Richou 1995
8/87
19/87
28.0 %
0.36 [ 0.15, 0.88 ]
87
87
28.0 %
0.36 [ 0.15, 0.88 ]
550
553
100.0 %
0.36 [ 0.22, 0.57 ]
Subtotal (95% CI)
Total events: 8 (Mirtazapine), 19 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.24 (P = 0.025)
Total (95% CI)
Total events: 29 (Mirtazapine), 74 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.16, df = 6 (P = 0.90); I2 =0.0%
Test for overall effect: Z = 4.30 (P = 0.000017)
Test for subgroup differences: Chi2 = 0.00, df = 1 (P = 0.97), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
98
Analysis 1.25. Comparison 1 Mirtazapine versus TCAs, Outcome 25 Sleep disturbance.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 25 Sleep disturbance
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
20/103
15/104
100.0 %
1.43 [ 0.69, 2.98 ]
103
104
100.0 %
1.43 [ 0.69, 2.98 ]
1 vs Amitriptyline
Organon 85146
Total (95% CI)
Total events: 20 (Mirtazapine), 15 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.96 (P = 0.34)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
99
Analysis 1.26. Comparison 1 Mirtazapine versus TCAs, Outcome 26 Sleepiness/Drowsiness/Somnolence.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 26 Sleepiness/Drowsiness/Somnolence
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
23/50
28/50
16.2 %
0.67 [ 0.30, 1.47 ]
Hoyberg 1996
4/56
7/59
6.3 %
0.57 [ 0.16, 2.07 ]
22/79
27/77
21.4 %
0.71 [ 0.36, 1.41 ]
27/103
31/104
26.1 %
0.84 [ 0.46, 1.54 ]
34/50
31/50
14.9 %
1.30 [ 0.57, 2.97 ]
338
340
84.9 %
0.81 [ 0.58, 1.14 ]
1 vs Amitriptyline
Mullin 1996
Organon 85146
Smith 1990
Subtotal (95% CI)
Total events: 110 (Mirtazapine), 124 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.92, df = 4 (P = 0.75); I2 =0.0%
Test for overall effect: Z = 1.21 (P = 0.23)
2 vs Doxepin
Marttila 1995
19/83
11/80
15.1 %
1.86 [ 0.82, 4.21 ]
83
80
15.1 %
1.86 [ 0.82, 4.21 ]
421
420
100.0 %
0.92 [ 0.66, 1.27 ]
Subtotal (95% CI)
Total events: 19 (Mirtazapine), 11 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.49 (P = 0.14)
Total (95% CI)
Total events: 129 (Mirtazapine), 135 (Others)
Heterogeneity: Tau2 = 0.01; Chi2 = 5.32, df = 5 (P = 0.38); I2 =6%
Test for overall effect: Z = 0.51 (P = 0.61)
Test for subgroup differences: Chi2 = 3.40, df = 1 (P = 0.07), I2 =71%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
100
Analysis 1.27. Comparison 1 Mirtazapine versus TCAs, Outcome 27 Suicide attempt.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 27 Suicide attempt
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
1/79
1/77
22.2 %
0.97 [ 0.06, 15.86 ]
2/103
0/104
18.6 %
5.15 [ 0.24, 108.55 ]
182
181
40.9 %
2.08 [ 0.27, 16.29 ]
1 vs Amitriptyline
Mullin 1996
Organon 85146
Subtotal (95% CI)
Total events: 3 (Mirtazapine), 1 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.64, df = 1 (P = 0.43); I2 =0.0%
Test for overall effect: Z = 0.70 (P = 0.49)
2 vs Clomipramine
Richou 1995
1/87
1/87
22.3 %
1.00 [ 0.06, 16.25 ]
87
87
22.3 %
1.00 [ 0.06, 16.25 ]
0/83
1/80
16.7 %
0.32 [ 0.01, 7.91 ]
83
80
16.7 %
0.32 [ 0.01, 7.91 ]
4/114
0/121
20.1 %
9.90 [ 0.53, 185.90 ]
114
121
20.1 %
9.90 [ 0.53, 185.90 ]
469
100.0 %
1.77 [ 0.47, 6.58 ]
Subtotal (95% CI)
Total events: 1 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 0 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.70 (P = 0.48)
4 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
Total events: 4 (Mirtazapine), 0 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.53 (P = 0.13)
Total (95% CI)
466
Total events: 8 (Mirtazapine), 3 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 3.31, df = 4 (P = 0.51); I2 =0.0%
Test for overall effect: Z = 0.85 (P = 0.40)
Test for subgroup differences: Chi2 = 2.61, df = 3 (P = 0.46), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
101
Analysis 1.28. Comparison 1 Mirtazapine versus TCAs, Outcome 28 Subgroup analysis: Response at 2
weeks: Treatment settings: Psychiatric inpatients.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 28 Subgroup analysis: Response at 2 weeks: Treatment settings: Psychiatric inpatients
Study or subgroup
Mirtazapine
Control
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
16/125
21/126
47.2 %
0.73 [ 0.36, 1.48 ]
125
126
47.2 %
0.73 [ 0.36, 1.48 ]
23/87
25/87
52.8 %
0.89 [ 0.46, 1.73 ]
87
87
52.8 %
0.89 [ 0.46, 1.73 ]
212
213
100.0 %
0.81 [ 0.50, 1.32 ]
1 vs Amitriptyline
Zivkov 1995
Subtotal (95% CI)
Total events: 16 (Mirtazapine), 21 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.86 (P = 0.39)
2 vs Clomipramine
Richou 1995
Subtotal (95% CI)
Total events: 23 (Mirtazapine), 25 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.34 (P = 0.73)
Total (95% CI)
Total events: 39 (Mirtazapine), 46 (Control)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.15, df = 1 (P = 0.69); I2 =0.0%
Test for overall effect: Z = 0.84 (P = 0.40)
Test for subgroup differences: Chi2 = 0.15, df = 1 (P = 0.69), I2 =0.0%
0.01
0.1
Favours experimental
1
10
100
Favours control
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
102
Analysis 1.29. Comparison 1 Mirtazapine versus TCAs, Outcome 29 Subgroup analysis: Response at end of
the acute-phase treatment: Treatment settings: Psychiatric inpatients.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 29 Subgroup analysis: Response at end of the acute-phase treatment: Treatment settings: Psychiatric inpatients
Study or subgroup
Mirtazapine
Control
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Organon 85146
53/103
62/104
34.8 %
0.72 [ 0.41, 1.24 ]
Zivkov 1995
81/125
80/126
39.6 %
1.06 [ 0.63, 1.77 ]
228
230
74.5 %
0.88 [ 0.60, 1.29 ]
1 vs Amitriptyline
Subtotal (95% CI)
Total events: 134 (Mirtazapine), 142 (Control)
Heterogeneity: Tau2 = 0.00; Chi2 = 1.02, df = 1 (P = 0.31); I2 =2%
Test for overall effect: Z = 0.65 (P = 0.52)
2 vs Clomipramine
Richou 1995
59/87
61/87
25.5 %
0.90 [ 0.47, 1.71 ]
87
87
25.5 %
0.90 [ 0.47, 1.71 ]
315
317
100.0 %
0.89 [ 0.64, 1.23 ]
Subtotal (95% CI)
Total events: 59 (Mirtazapine), 61 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.33 (P = 0.74)
Total (95% CI)
Total events: 193 (Mirtazapine), 203 (Control)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.02, df = 2 (P = 0.60); I2 =0.0%
Test for overall effect: Z = 0.73 (P = 0.47)
Test for subgroup differences: Chi2 = 0.00, df = 1 (P = 0.96), I2 =0.0%
0.01
0.1
Favours experimental
1
10
100
Favours control
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
103
Analysis 1.30. Comparison 1 Mirtazapine versus TCAs, Outcome 30 Sensitivity analysis: Response at 2
weeks: Studies without imputation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 30 Sensitivity analysis: Response at 2 weeks: Studies without imputation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
7/50
8/50
7.2 %
0.85 [ 0.28, 2.57 ]
Mullin 1996
18/79
23/77
16.8 %
0.69 [ 0.34, 1.42 ]
Smith 1990
18/50
20/50
13.3 %
0.84 [ 0.38, 1.89 ]
Zivkov 1995
16/125
21/126
17.5 %
0.73 [ 0.36, 1.48 ]
304
303
54.8 %
0.76 [ 0.51, 1.13 ]
1 vs Amitriptyline
Bremner 1995
Subtotal (95% CI)
Total events: 59 (Mirtazapine), 72 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.18, df = 3 (P = 0.98); I2 =0.0%
Test for overall effect: Z = 1.35 (P = 0.18)
2 vs Clomipramine
Richou 1995
23/87
25/87
19.6 %
0.89 [ 0.46, 1.73 ]
87
87
19.6 %
0.89 [ 0.46, 1.73 ]
30/83
27/80
20.9 %
1.11 [ 0.58, 2.12 ]
83
80
20.9 %
1.11 [ 0.58, 2.12 ]
4/114
5/121
4.8 %
0.84 [ 0.22, 3.22 ]
114
121
4.8 %
0.84 [ 0.22, 3.22 ]
588
591
100.0 %
0.85 [ 0.64, 1.15 ]
Subtotal (95% CI)
Total events: 23 (Mirtazapine), 25 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.34 (P = 0.73)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 30 (Mirtazapine), 27 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.32 (P = 0.75)
4 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
Total events: 4 (Mirtazapine), 5 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.25 (P = 0.80)
Total (95% CI)
Total events: 116 (Mirtazapine), 129 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.16, df = 6 (P = 0.98); I2 =0.0%
Test for overall effect: Z = 1.06 (P = 0.29)
Test for subgroup differences: Chi2 = 0.98, df = 3 (P = 0.81), I2 =0.0%
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
104
Analysis 1.31. Comparison 1 Mirtazapine versus TCAs, Outcome 31 Sensitivity analysis: Response at end of
the acute-phase treatment: Studies without imputation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 1 Mirtazapine versus TCAs
Outcome: 31 Sensitivity analysis: Response at end of the acute-phase treatment: Studies without imputation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Bremner 1995
31/50
24/50
7.5 %
1.77 [ 0.80, 3.92 ]
Mullin 1996
38/79
41/77
12.0 %
0.81 [ 0.43, 1.53 ]
53/103
62/104
15.7 %
0.72 [ 0.41, 1.24 ]
Smith 1990
25/50
26/50
7.7 %
0.92 [ 0.42, 2.02 ]
Zivkov 1995
81/125
80/126
17.9 %
1.06 [ 0.63, 1.77 ]
407
407
60.9 %
0.95 [ 0.72, 1.26 ]
1 vs Amitriptyline
Organon 85146
Subtotal (95% CI)
Total events: 228 (Mirtazapine), 233 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 3.74, df = 4 (P = 0.44); I2 =0.0%
Test for overall effect: Z = 0.35 (P = 0.73)
2 vs Clomipramine
Richou 1995
59/87
61/87
11.5 %
0.90 [ 0.47, 1.71 ]
87
87
11.5 %
0.90 [ 0.47, 1.71 ]
54/83
55/80
11.1 %
0.85 [ 0.44, 1.63 ]
83
80
11.1 %
0.85 [ 0.44, 1.63 ]
38/114
43/121
16.4 %
0.91 [ 0.53, 1.55 ]
114
121
16.4 %
0.91 [ 0.53, 1.55 ]
Subtotal (95% CI)
Total events: 59 (Mirtazapine), 61 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.33 (P = 0.74)
3 vs Doxepin
Marttila 1995
Subtotal (95% CI)
Total events: 54 (Mirtazapine), 55 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.50 (P = 0.62)
4 vs Nortriptyline
Fava 2006
Subtotal (95% CI)
Total events: 38 (Mirtazapine), 43 (Others)
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
105
(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
691
695
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Heterogeneity: not applicable
Test for overall effect: Z = 0.36 (P = 0.72)
Total (95% CI)
100.0 %
0.93 [ 0.74, 1.15 ]
Total events: 379 (Mirtazapine), 392 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 3.86, df = 7 (P = 0.80); I2 =0.0%
Test for overall effect: Z = 0.69 (P = 0.49)
Test for subgroup differences: Chi2 = 0.12, df = 3 (P = 0.99), I2 =0.0%
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 1.32. Comparison 1 Mirtazapine versus TCAs, Outcome 32 Secondary outcome (SKEWED DATA:
depression severity) at 2 weeks.
Secondary outcome (SKEWED DATA: depression severity) at 2 weeks
Study
Comparator drug
Measurement
Mirtazapine: mean
Hoyberg
1996
Amitriptyline
HAMD-4.7
21 change
score
SD
N
Comparator:
mean
SD
N
4.5
54
-5.2
4.4
59
note
Analysis 1.33. Comparison 1 Mirtazapine versus TCAs, Outcome 33 Secondary outcome (SKEWED DATA:
depression severity) at end of the acute-phase treatment.
Secondary outcome (SKEWED DATA: depression severity) at end of the acute-phase treatment
Study
Comparator
Measurement
Hoyberg
1996
Amitriptyline
Marttila
1995
Mirtazapine: mean
SD
N
Comparator:
mean
SD
N
HAMD-11.1
21 change
score
7.9
54
-13.1
7.5
59
Doxepin
HAMD17
9.15
7.5
83
9.0
6.35
80
Mullin
1996
Amitriptyline
HAMD17
11.7
7.3
71
10.7
6.8
71
Zivkov
1995
Amitriptyline
HAMD21
12.8
10.1
113
12.0
10.0
111
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Note
106
Analysis 2.1. Comparison 2 Mirtazapine versus SSRIs, Outcome 1 Primary outcome (response) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 1 Primary outcome (response) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
21/137
11/133
5.7 %
2.01 [ 0.93, 4.35 ]
137
133
5.7 %
2.01 [ 0.93, 4.35 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 21 (Mirtazapine), 11 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.77 (P = 0.077)
2 vs Fluoxetine
Amini 2005
4/18
3/18
1.2 %
1.43 [ 0.27, 7.55 ]
Hong 2003
20/66
21/66
6.2 %
0.93 [ 0.45, 1.95 ]
31/147
25/152
9.9 %
1.36 [ 0.76, 2.43 ]
16/66
11/67
4.6 %
1.63 [ 0.69, 3.84 ]
2/9
3/13
0.8 %
0.95 [ 0.12, 7.28 ]
306
316
22.8 %
1.26 [ 0.86, 1.85 ]
Versiani 2005
Wheatley 1998
Winokur 2003
Subtotal (95% CI)
Total events: 73 (Mirtazapine), 63 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.15, df = 4 (P = 0.89); I2 =0.0%
Test for overall effect: Z = 1.17 (P = 0.24)
3 vs Paroxetine
Benkert 2000
40/139
27/136
10.8 %
1.63 [ 0.93, 2.85 ]
Schatzberg 2002
35/128
16/126
7.9 %
2.59 [ 1.35, 4.97 ]
22/99
6/98
3.7 %
4.38 [ 1.69, 11.35 ]
366
360
22.5 %
2.39 [ 1.42, 4.02 ]
Wade 2003
Subtotal (95% CI)
Total events: 97 (Mirtazapine), 49 (Others)
Heterogeneity: Tau2 = 0.08; Chi2 = 3.34, df = 2 (P = 0.19); I2 =40%
Test for overall effect: Z = 3.29 (P = 0.0010)
4 vs Sertraline
Behnke 2003
83/176
62/170
18.3 %
1.55 [ 1.01, 2.39 ]
Thase 2000
47/124
40/126
12.4 %
1.31 [ 0.78, 2.21 ]
300
296
30.7 %
1.45 [ 1.04, 2.02 ]
Subtotal (95% CI)
Total events: 130 (Mirtazapine), 102 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.24, df = 1 (P = 0.62); I2 =0.0%
Test for overall effect: Z = 2.20 (P = 0.028)
5 vs Fluvoxamine
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
107
(. . .
Mirtazapine
n/N
n/N
Schoemaker 2002
65/205
52/207
18.3 %
1.38 [ 0.90, 2.13 ]
205
207
18.3 %
1.38 [ 0.90, 2.13 ]
1312
100.0 %
1.57 [ 1.30, 1.88 ]
Subtotal (95% CI)
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Study or subgroup
Total events: 65 (Mirtazapine), 52 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.48 (P = 0.14)
Total (95% CI)
1314
Total events: 386 (Mirtazapine), 277 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 10.33, df = 11 (P = 0.50); I2 =0.0%
Test for overall effect: Z = 4.79 (P < 0.00001)
Test for subgroup differences: Chi2 = 4.59, df = 4 (P = 0.33), I2 =13%
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 2.2. Comparison 2 Mirtazapine versus SSRIs, Outcome 2 Primary outcome (response) at end of
the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 2 Primary outcome (response) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
116/137
117/133
5.4 %
0.76 [ 0.38, 1.52 ]
137
133
5.4 %
0.76 [ 0.38, 1.52 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 116 (Mirtazapine), 117 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.79 (P = 0.43)
2 vs Fluoxetine
Amini 2005
12/18
8/18
1.4 %
2.50 [ 0.65, 9.65 ]
Hong 2003
35/66
30/66
5.6 %
1.35 [ 0.68, 2.69 ]
106/147
104/152
10.7 %
1.19 [ 0.73, 1.96 ]
Versiani 2005
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
108
(. . .
Study or subgroup
Wheatley 1998
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
39/66
28/67
5.5 %
2.01 [ 1.01, 4.01 ]
8/9
6/13
0.5 %
9.33 [ 0.89, 97.62 ]
306
316
23.8 %
1.55 [ 1.07, 2.23 ]
Winokur 2003
Subtotal (95% CI)
Total events: 200 (Mirtazapine), 176 (Others)
Heterogeneity: Tau2 = 0.02; Chi2 = 4.48, df = 4 (P = 0.35); I2 =11%
Test for overall effect: Z = 2.33 (P = 0.020)
3 vs Paroxetine
Benkert 2000
74/139
66/136
11.8 %
1.21 [ 0.75, 1.94 ]
Schatzberg 2002
72/128
60/126
10.8 %
1.41 [ 0.86, 2.32 ]
38/99
34/98
7.8 %
1.17 [ 0.66, 2.10 ]
366
360
30.4 %
1.27 [ 0.94, 1.70 ]
Wade 2003
Subtotal (95% CI)
Total events: 184 (Mirtazapine), 160 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.30, df = 2 (P = 0.86); I2 =0.0%
Test for overall effect: Z = 1.58 (P = 0.11)
4 vs Sertraline
Behnke 2003
117/176
114/170
13.2 %
0.97 [ 0.62, 1.52 ]
Thase 2000
61/124
63/126
10.7 %
0.97 [ 0.59, 1.59 ]
300
296
23.9 %
0.97 [ 0.70, 1.35 ]
Subtotal (95% CI)
Total events: 178 (Mirtazapine), 177 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.00, df = 1 (P = 0.99); I2 =0.0%
Test for overall effect: Z = 0.17 (P = 0.86)
5 vs Fluvoxamine
Schoemaker 2002
132/205
127/207
16.5 %
1.14 [ 0.76, 1.70 ]
205
207
16.5 %
1.14 [ 0.76, 1.70 ]
1312
100.0 %
1.19 [ 1.01, 1.39 ]
Subtotal (95% CI)
Total events: 132 (Mirtazapine), 127 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.64 (P = 0.52)
Total (95% CI)
1314
Total events: 810 (Mirtazapine), 757 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 10.06, df = 11 (P = 0.53); I2 =0.0%
Test for overall effect: Z = 2.05 (P = 0.040)
Test for subgroup differences: Chi2 = 5.24, df = 4 (P = 0.26), I2 =24%
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
109
Analysis 2.3. Comparison 2 Mirtazapine versus SSRIs, Outcome 3 Primary outcome (response) at end of
the continuation treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 3 Primary outcome (response) at end of the continuation treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
59/99
47/98
100.0 %
1.60 [ 0.91, 2.81 ]
99
98
100.0 %
1.60 [ 0.91, 2.81 ]
1 vs Paroxetine
Wade 2003
Total (95% CI)
Total events: 59 (Mirtazapine), 47 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.63 (P = 0.10)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
110
Analysis 2.4. Comparison 2 Mirtazapine versus SSRIs, Outcome 4 Secondary outcome (remission) at 2
weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 4 Secondary outcome (remission) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
5/137
2/133
3.1 %
2.48 [ 0.47, 13.02 ]
137
133
3.1 %
2.48 [ 0.47, 13.02 ]
Amini 2005
2/18
1/18
1.4 %
2.13 [ 0.18, 25.78 ]
Hong 2003
8/66
7/66
7.3 %
1.16 [ 0.40, 3.41 ]
9/147
3/152
4.8 %
3.24 [ 0.86, 12.21 ]
Wheatley 1998
3/66
2/67
2.6 %
1.55 [ 0.25, 9.58 ]
Winokur 2003
1/9
2/13
1.3 %
0.69 [ 0.05, 8.96 ]
306
316
17.3 %
1.63 [ 0.81, 3.27 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 5 (Mirtazapine), 2 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.07 (P = 0.28)
2 vs Fluoxetine
Versiani 2005
Subtotal (95% CI)
Total events: 23 (Mirtazapine), 15 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.89, df = 4 (P = 0.76); I2 =0.0%
Test for overall effect: Z = 1.36 (P = 0.17)
3 vs Paroxetine
Benkert 2000
18/139
12/136
14.2 %
1.54 [ 0.71, 3.33 ]
Schatzberg 2002
14/128
5/126
7.7 %
2.97 [ 1.04, 8.52 ]
6/99
0/98
1.0 %
13.70 [ 0.76, 246.50 ]
366
360
22.9 %
2.31 [ 1.04, 5.11 ]
Wade 2003
Subtotal (95% CI)
Total events: 38 (Mirtazapine), 17 (Others)
Heterogeneity: Tau2 = 0.15; Chi2 = 2.75, df = 2 (P = 0.25); I2 =27%
Test for overall effect: Z = 2.06 (P = 0.040)
4 vs Sertraline
Behnke 2003
39/176
24/170
27.1 %
1.73 [ 0.99, 3.03 ]
Thase 2000
15/124
6/126
8.8 %
2.75 [ 1.03, 7.35 ]
300
296
35.9 %
1.94 [ 1.19, 3.15 ]
Subtotal (95% CI)
Total events: 54 (Mirtazapine), 30 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.65, df = 1 (P = 0.42); I2 =0.0%
Test for overall effect: Z = 2.67 (P = 0.0075)
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
111
(. . .
Study or subgroup
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Mirtazapine
Others
n/N
n/N
25/205
18/207
20.8 %
1.46 [ 0.77, 2.76 ]
205
207
20.8 %
1.46 [ 0.77, 2.76 ]
1312
100.0 %
1.82 [ 1.36, 2.44 ]
5 vs Fluvoxamine
Schoemaker 2002
Subtotal (95% CI)
Total events: 25 (Mirtazapine), 18 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.16 (P = 0.25)
Total (95% CI)
1314
Total events: 145 (Mirtazapine), 82 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 6.24, df = 11 (P = 0.86); I2 =0.0%
Test for overall effect: Z = 4.04 (P = 0.000054)
Test for subgroup differences: Chi2 = 1.10, df = 4 (P = 0.89), I2 =0.0%
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 2.5. Comparison 2 Mirtazapine versus SSRIs, Outcome 5 Secondary outcome (remission) at end of
the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 5 Secondary outcome (remission) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
89/137
89/133
10.3 %
0.92 [ 0.55, 1.52 ]
137
133
10.3 %
0.92 [ 0.55, 1.52 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 89 (Mirtazapine), 89 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.34 (P = 0.73)
2 vs Fluoxetine
Amini 2005
7/18
4/18
1.4 %
2.23 [ 0.52, 9.59 ]
Hong 2003
21/66
16/66
4.9 %
1.46 [ 0.68, 3.13 ]
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Study or subgroup
Versiani 2005
Wheatley 1998
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
58/147
61/152
11.7 %
0.97 [ 0.61, 1.54 ]
14/66
16/67
4.4 %
0.86 [ 0.38, 1.94 ]
5/9
4/13
1.0 %
2.81 [ 0.48, 16.43 ]
306
316
23.5 %
1.12 [ 0.80, 1.57 ]
Winokur 2003
Subtotal (95% CI)
Total events: 105 (Mirtazapine), 101 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 3.12, df = 4 (P = 0.54); I2 =0.0%
Test for overall effect: Z = 0.66 (P = 0.51)
3 vs Paroxetine
Benkert 2000
52/139
42/136
10.4 %
1.34 [ 0.81, 2.21 ]
Schatzberg 2002
48/128
35/126
9.4 %
1.56 [ 0.92, 2.65 ]
52/99
35/98
8.3 %
1.99 [ 1.12, 3.53 ]
366
360
28.1 %
1.58 [ 1.16, 2.15 ]
Wade 2003
Subtotal (95% CI)
Total events: 152 (Mirtazapine), 112 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.06, df = 2 (P = 0.59); I2 =0.0%
Test for overall effect: Z = 2.92 (P = 0.0035)
4 vs Sertraline
Behnke 2003
76/176
73/170
13.4 %
1.01 [ 0.66, 1.55 ]
Thase 2000
45/124
35/126
9.3 %
1.48 [ 0.87, 2.53 ]
300
296
22.7 %
1.18 [ 0.82, 1.71 ]
Subtotal (95% CI)
Total events: 121 (Mirtazapine), 108 (Others)
Heterogeneity: Tau2 = 0.01; Chi2 = 1.21, df = 1 (P = 0.27); I2 =17%
Test for overall effect: Z = 0.88 (P = 0.38)
5 vs Fluvoxamine
Schoemaker 2002
89/205
99/207
15.4 %
0.84 [ 0.57, 1.23 ]
205
207
15.4 %
0.84 [ 0.57, 1.23 ]
1312
100.0 %
1.17 [ 0.98, 1.40 ]
Subtotal (95% CI)
Total events: 89 (Mirtazapine), 99 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.90 (P = 0.37)
Total (95% CI)
1314
Total events: 556 (Mirtazapine), 509 (Others)
Heterogeneity: Tau2 = 0.01; Chi2 = 12.88, df = 11 (P = 0.30); I2 =15%
Test for overall effect: Z = 1.78 (P = 0.075)
Test for subgroup differences: Chi2 = 7.50, df = 4 (P = 0.11), I2 =47%
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
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Analysis 2.6. Comparison 2 Mirtazapine versus SSRIs, Outcome 6 Secondary outcome (remission) at end of
the continuation treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 6 Secondary outcome (remission) at end of the continuation treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
35/99
22/98
100.0 %
1.89 [ 1.01, 3.54 ]
99
98
100.0 %
1.89 [ 1.01, 3.54 ]
1 vs Paroxetine
Wade 2003
Total (95% CI)
Total events: 35 (Mirtazapine), 22 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.98 (P = 0.047)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Analysis 2.7. Comparison 2 Mirtazapine versus SSRIs, Outcome 7 Secondary outcome (withdrawal due to
any reason).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 7 Secondary outcome (withdrawal due to any reason)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
18/137
8/133
5.9 %
2.36 [ 0.99, 5.64 ]
137
133
5.9 %
2.36 [ 0.99, 5.64 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 18 (Mirtazapine), 8 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.94 (P = 0.053)
2 vs Fluoxetine
Amini 2005
2/18
3/18
1.4 %
0.63 [ 0.09, 4.28 ]
Hong 2003
30/66
22/66
8.4 %
1.67 [ 0.82, 3.37 ]
Wheatley 1998
17/66
21/67
7.5 %
0.76 [ 0.36, 1.62 ]
1/9
2/13
0.8 %
0.69 [ 0.05, 8.96 ]
159
164
18.0 %
1.09 [ 0.67, 1.78 ]
Winokur 2003
Subtotal (95% CI)
Total events: 50 (Mirtazapine), 48 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.72, df = 3 (P = 0.44); I2 =0.0%
Test for overall effect: Z = 0.35 (P = 0.73)
3 vs Paroxetine
Benkert 2000
30/139
33/136
11.8 %
0.86 [ 0.49, 1.51 ]
Schatzberg 2002
29/128
39/126
11.8 %
0.65 [ 0.37, 1.14 ]
53/99
55/98
11.8 %
0.90 [ 0.51, 1.58 ]
366
360
35.4 %
0.80 [ 0.58, 1.10 ]
Wade 2003
Subtotal (95% CI)
Total events: 112 (Mirtazapine), 127 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.73, df = 2 (P = 0.69); I2 =0.0%
Test for overall effect: Z = 1.38 (P = 0.17)
4 vs Sertraline
Behnke 2003
41/176
32/170
13.1 %
1.31 [ 0.78, 2.20 ]
Thase 2000
47/124
34/126
12.6 %
1.65 [ 0.97, 2.82 ]
300
296
25.8 %
1.47 [ 1.01, 2.13 ]
Subtotal (95% CI)
Total events: 88 (Mirtazapine), 66 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.37, df = 1 (P = 0.54); I2 =0.0%
Test for overall effect: Z = 2.01 (P = 0.044)
5 vs Fluvoxamine
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Mirtazapine
n/N
n/N
Schoemaker 2002
47/205
41/207
14.9 %
1.20 [ 0.75, 1.93 ]
205
207
14.9 %
1.20 [ 0.75, 1.93 ]
1160
100.0 %
1.12 [ 0.89, 1.40 ]
Subtotal (95% CI)
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Study or subgroup
Total events: 47 (Mirtazapine), 41 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.77 (P = 0.44)
Total (95% CI)
1167
Total events: 315 (Mirtazapine), 290 (Others)
Heterogeneity: Tau2 = 0.03; Chi2 = 13.00, df = 10 (P = 0.22); I2 =23%
Test for overall effect: Z = 0.94 (P = 0.35)
Test for subgroup differences: Chi2 = 9.18, df = 4 (P = 0.06), I2 =56%
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.8. Comparison 2 Mirtazapine versus SSRIs, Outcome 8 Secondary outcome (withdrawal due to
adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 8 Secondary outcome (withdrawal due to adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
8/137
4/133
6.5 %
2.00 [ 0.59, 6.81 ]
137
133
6.5 %
2.00 [ 0.59, 6.81 ]
Amini 2005
1/18
2/18
2.2 %
0.47 [ 0.04, 5.71 ]
Hong 2003
13/66
8/66
8.7 %
1.78 [ 0.68, 4.63 ]
12/147
13/152
10.1 %
0.95 [ 0.42, 2.16 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 8 (Mirtazapine), 4 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.11 (P = 0.27)
2 vs Fluoxetine
Versiani 2005
0.05
0.2
Favours Mirtazapine
1
5
20
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Study or subgroup
Mirtazapine
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
7/66
9/67
7.8 %
0.76 [ 0.27, 2.19 ]
297
303
28.8 %
1.05 [ 0.62, 1.78 ]
Wheatley 1998
Subtotal (95% CI)
Others
Total events: 33 (Mirtazapine), 32 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.97, df = 3 (P = 0.58); I2 =0.0%
Test for overall effect: Z = 0.20 (P = 0.85)
3 vs Paroxetine
Benkert 2000
12/139
10/136
9.5 %
1.19 [ 0.50, 2.85 ]
Schatzberg 2002
19/128
33/126
12.3 %
0.49 [ 0.26, 0.92 ]
21/99
24/98
11.8 %
0.83 [ 0.43, 1.62 ]
366
360
33.6 %
0.74 [ 0.45, 1.21 ]
Wade 2003
Subtotal (95% CI)
Total events: 52 (Mirtazapine), 67 (Others)
Heterogeneity: Tau2 = 0.06; Chi2 = 2.87, df = 2 (P = 0.24); I2 =30%
Test for overall effect: Z = 1.21 (P = 0.23)
4 vs Sertraline
Behnke 2003
21/176
5/170
8.3 %
4.47 [ 1.65, 12.15 ]
Thase 2000
23/124
12/126
10.9 %
2.16 [ 1.02, 4.57 ]
300
296
19.2 %
2.88 [ 1.43, 5.77 ]
Subtotal (95% CI)
Total events: 44 (Mirtazapine), 17 (Others)
Heterogeneity: Tau2 = 0.06; Chi2 = 1.31, df = 1 (P = 0.25); I2 =24%
Test for overall effect: Z = 2.97 (P = 0.0030)
5 vs Fluvoxamine
Schoemaker 2002
25/205
16/207
11.9 %
1.66 [ 0.86, 3.21 ]
205
207
11.9 %
1.66 [ 0.86, 3.21 ]
1299
100.0 %
1.26 [ 0.85, 1.86 ]
Subtotal (95% CI)
Total events: 25 (Mirtazapine), 16 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.50 (P = 0.13)
Total (95% CI)
1305
Total events: 162 (Mirtazapine), 136 (Others)
Heterogeneity: Tau2 = 0.22; Chi2 = 21.79, df = 10 (P = 0.02); I2 =54%
Test for overall effect: Z = 1.14 (P = 0.25)
Test for subgroup differences: Chi2 = 11.57, df = 4 (P = 0.02), I2 =65%
0.05
0.2
Favours Mirtazapine
1
5
20
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
117
Analysis 2.9. Comparison 2 Mirtazapine versus SSRIs, Outcome 9 Secondary outcome (having some
adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 9 Secondary outcome (having some adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
91/137
94/133
15.7 %
0.82 [ 0.49, 1.37 ]
137
133
15.7 %
0.82 [ 0.49, 1.37 ]
47/66
38/66
8.5 %
1.82 [ 0.88, 3.75 ]
73/147
66/152
19.5 %
1.29 [ 0.82, 2.03 ]
213
218
27.9 %
1.42 [ 0.97, 2.09 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 91 (Mirtazapine), 94 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.75 (P = 0.45)
2 vs Fluoxetine
Hong 2003
Versiani 2005
Subtotal (95% CI)
Total events: 120 (Mirtazapine), 104 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.64, df = 1 (P = 0.42); I2 =0.0%
Test for overall effect: Z = 1.78 (P = 0.075)
3 vs Paroxetine
Benkert 2000
Schatzberg 2002
Wade 2003
92/139
85/136
16.9 %
1.17 [ 0.72, 1.92 ]
102/128
104/126
10.9 %
0.83 [ 0.44, 1.56 ]
78/99
83/98
8.3 %
0.67 [ 0.32, 1.39 ]
366
360
36.1 %
0.94 [ 0.66, 1.32 ]
Subtotal (95% CI)
Total events: 272 (Mirtazapine), 272 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.75, df = 2 (P = 0.42); I2 =0.0%
Test for overall effect: Z = 0.37 (P = 0.71)
4 vs Sertraline
Behnke 2003
113/176
115/170
20.2 %
0.86 [ 0.55, 1.34 ]
176
170
20.2 %
0.86 [ 0.55, 1.34 ]
881
100.0 %
1.01 [ 0.81, 1.26 ]
Subtotal (95% CI)
Total events: 113 (Mirtazapine), 115 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.68 (P = 0.50)
Total (95% CI)
892
Total events: 596 (Mirtazapine), 585 (Others)
Heterogeneity: Tau2 = 0.01; Chi2 = 6.71, df = 6 (P = 0.35); I2 =11%
Test for overall effect: Z = 0.10 (P = 0.92)
Test for subgroup differences: Chi2 = 4.32, df = 3 (P = 0.23), I2 =31%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Analysis 2.10. Comparison 2 Mirtazapine versus SSRIs, Outcome 10 Hypotension/Bradycardia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 10 Hypotension/Bradycardia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Wheatley 1998
5/66
1/67
100.0 %
5.41 [ 0.61, 47.62 ]
Total (95% CI)
66
67
100.0 %
5.41 [ 0.61, 47.62 ]
1 vs Fluoxetine
Total events: 5 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.52 (P = 0.13)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.11. Comparison 2 Mirtazapine versus SSRIs, Outcome 11 Sweating.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 11 Sweating
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
3/137
20/133
19.3 %
0.13 [ 0.04, 0.44 ]
137
133
19.3 %
0.13 [ 0.04, 0.44 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 3 (Mirtazapine), 20 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 3.27 (P = 0.0011)
2 vs Paroxetine
Benkert 2000
3/139
10/136
17.2 %
0.28 [ 0.07, 1.03 ]
Schatzberg 2002
8/128
17/126
38.4 %
0.43 [ 0.18, 1.03 ]
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
119
(. . .
Study or subgroup
Mirtazapine
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
2/99
11/98
12.6 %
0.16 [ 0.04, 0.76 ]
366
360
68.2 %
0.32 [ 0.17, 0.62 ]
Wade 2003
Subtotal (95% CI)
Others
Total events: 13 (Mirtazapine), 38 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.21, df = 2 (P = 0.55); I2 =0.0%
Test for overall effect: Z = 3.38 (P = 0.00073)
3 vs Sertraline
Behnke 2003
Subtotal (95% CI)
2/176
9/170
12.4 %
0.21 [ 0.04, 0.97 ]
176
170
12.4 %
0.21 [ 0.04, 0.97 ]
663
100.0 %
0.25 [ 0.15, 0.44 ]
Total events: 2 (Mirtazapine), 9 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.00 (P = 0.045)
Total (95% CI)
679
Total events: 18 (Mirtazapine), 67 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 3.01, df = 4 (P = 0.56); I2 =0.0%
Test for overall effect: Z = 4.93 (P < 0.00001)
Test for subgroup differences: Chi2 = 1.77, df = 2 (P = 0.41), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
120
Analysis 2.12. Comparison 2 Mirtazapine versus SSRIs, Outcome 12 Constipation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 12 Constipation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Amini 2005
4/18
1/18
3.3 %
4.86 [ 0.49, 48.57 ]
Hong 2003
10/66
6/66
15.2 %
1.79 [ 0.61, 5.24 ]
84
84
18.5 %
2.14 [ 0.81, 5.66 ]
1 vs Fluoxetine
Subtotal (95% CI)
Total events: 14 (Mirtazapine), 7 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.60, df = 1 (P = 0.44); I2 =0.0%
Test for overall effect: Z = 1.53 (P = 0.13)
2 vs Paroxetine
Benkert 2000
10/139
9/136
20.2 %
1.09 [ 0.43, 2.78 ]
Schatzberg 2002
15/128
14/126
29.4 %
1.06 [ 0.49, 2.30 ]
267
262
49.6 %
1.07 [ 0.59, 1.95 ]
Subtotal (95% CI)
Total events: 25 (Mirtazapine), 23 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.00, df = 1 (P = 0.96); I2 =0.0%
Test for overall effect: Z = 0.24 (P = 0.81)
3 vs Fluvoxamine
Schoemaker 2002
15/205
15/207
31.9 %
1.01 [ 0.48, 2.12 ]
205
207
31.9 %
1.01 [ 0.48, 2.12 ]
553
100.0 %
1.20 [ 0.79, 1.82 ]
Subtotal (95% CI)
Total events: 15 (Mirtazapine), 15 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.03 (P = 0.98)
Total (95% CI)
556
Total events: 54 (Mirtazapine), 45 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.28, df = 4 (P = 0.68); I2 =0.0%
Test for overall effect: Z = 0.84 (P = 0.40)
Test for subgroup differences: Chi2 = 1.68, df = 2 (P = 0.43), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
121
Analysis 2.13. Comparison 2 Mirtazapine versus SSRIs, Outcome 13 Diarrhoea.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 13 Diarrhoea
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
4/137
8/133
7.5 %
0.47 [ 0.14, 1.60 ]
137
133
7.5 %
0.47 [ 0.14, 1.60 ]
1/18
1/18
1.4 %
1.00 [ 0.06, 17.33 ]
18
18
1.4 %
1.00 [ 0.06, 17.33 ]
Benkert 2000
11/139
11/136
14.8 %
0.98 [ 0.41, 2.33 ]
Schatzberg 2002
19/128
22/126
25.0 %
0.82 [ 0.42, 1.61 ]
5/99
5/98
6.9 %
0.99 [ 0.28, 3.53 ]
366
360
46.8 %
0.89 [ 0.55, 1.46 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 4 (Mirtazapine), 8 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.21 (P = 0.23)
2 vs Fluoxetine
Amini 2005
Subtotal (95% CI)
Total events: 1 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
3 vs Paroxetine
Wade 2003
Subtotal (95% CI)
Total events: 35 (Mirtazapine), 38 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.12, df = 2 (P = 0.94); I2 =0.0%
Test for overall effect: Z = 0.45 (P = 0.65)
4 vs Sertraline
Behnke 2003
7/176
16/170
13.4 %
0.40 [ 0.16, 1.00 ]
Thase 2000
10/124
25/126
18.5 %
0.35 [ 0.16, 0.77 ]
300
296
31.9 %
0.37 [ 0.21, 0.67 ]
Subtotal (95% CI)
Total events: 17 (Mirtazapine), 41 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.04, df = 1 (P = 0.85); I2 =0.0%
Test for overall effect: Z = 3.26 (P = 0.0011)
5 vs Fluvoxamine
Schoemaker 2002
6/205
17/207
12.4 %
0.34 [ 0.13, 0.87 ]
Subtotal (95% CI)
205
207
12.4 %
0.34 [ 0.13, 0.87 ]
Total events: 6 (Mirtazapine), 17 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.24 (P = 0.025)
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Study or subgroup
Total (95% CI)
Mirtazapine
Others
n/N
n/N
1026
1014
Odds Ratio
MH,Random,95%
CI
Weight
100.0 %
Continued)
Odds Ratio
MH,Random,95%
CI
0.57 [ 0.41, 0.80 ]
Total events: 63 (Mirtazapine), 105 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 6.79, df = 7 (P = 0.45); I2 =0.0%
Test for overall effect: Z = 3.27 (P = 0.0011)
Test for subgroup differences: Chi2 = 6.62, df = 4 (P = 0.16), I2 =40%
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.14. Comparison 2 Mirtazapine versus SSRIs, Outcome 14 Dry mouth/Decreased salivation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 14 Dry mouth/Decreased salivation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
20/137
12/133
12.4 %
1.72 [ 0.81, 3.68 ]
137
133
12.4 %
1.72 [ 0.81, 3.68 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 20 (Mirtazapine), 12 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.41 (P = 0.16)
2 vs Fluoxetine
Amini 2005
4/18
1/18
1.4 %
4.86 [ 0.49, 48.57 ]
Hong 2003
7/66
3/66
3.8 %
2.49 [ 0.62, 10.09 ]
12/66
3/67
4.3 %
4.74 [ 1.27, 17.68 ]
150
151
9.5 %
3.68 [ 1.52, 8.91 ]
11.7 %
1.80 [ 0.82, 3.94 ]
Wheatley 1998
Subtotal (95% CI)
Total events: 23 (Mirtazapine), 7 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.50, df = 2 (P = 0.78); I2 =0.0%
Test for overall effect: Z = 2.88 (P = 0.0039)
3 vs Paroxetine
Benkert 2000
19/139
11/136
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
123
(. . .
Study or subgroup
Schatzberg 2002
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
34/128
13/126
14.6 %
3.14 [ 1.57, 6.30 ]
9/99
11/98
8.4 %
0.79 [ 0.31, 2.00 ]
366
360
34.7 %
1.73 [ 0.81, 3.70 ]
Wade 2003
Subtotal (95% CI)
Total events: 62 (Mirtazapine), 35 (Others)
Heterogeneity: Tau2 = 0.29; Chi2 = 5.45, df = 2 (P = 0.07); I2 =63%
Test for overall effect: Z = 1.42 (P = 0.16)
4 vs Sertraline
Behnke 2003
20/176
12/170
12.7 %
1.69 [ 0.80, 3.57 ]
Thase 2000
21/124
16/126
14.3 %
1.40 [ 0.69, 2.83 ]
300
296
27.0 %
1.53 [ 0.92, 2.55 ]
Subtotal (95% CI)
Total events: 41 (Mirtazapine), 28 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.13, df = 1 (P = 0.72); I2 =0.0%
Test for overall effect: Z = 1.62 (P = 0.10)
5 vs Fluvoxamine
Schoemaker 2002
24/205
17/207
16.4 %
1.48 [ 0.77, 2.85 ]
205
207
16.4 %
1.48 [ 0.77, 2.85 ]
1147
100.0 %
1.80 [ 1.37, 2.36 ]
Subtotal (95% CI)
Total events: 24 (Mirtazapine), 17 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.18 (P = 0.24)
Total (95% CI)
1158
Total events: 170 (Mirtazapine), 99 (Others)
Heterogeneity: Tau2 = 0.01; Chi2 = 9.37, df = 9 (P = 0.40); I2 =4%
Test for overall effect: Z = 4.19 (P = 0.000027)
Test for subgroup differences: Chi2 = 3.22, df = 4 (P = 0.52), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Analysis 2.15. Comparison 2 Mirtazapine versus SSRIs, Outcome 15 Nausea/Vomiting/Gastric distress.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 15 Nausea/Vomiting/Gastric distress
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
14/137
27/133
13.1 %
0.45 [ 0.22, 0.90 ]
137
133
13.1 %
0.45 [ 0.22, 0.90 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 14 (Mirtazapine), 27 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.27 (P = 0.023)
2 vs Fluoxetine
Amini 2005
2/18
7/18
2.1 %
0.20 [ 0.03, 1.13 ]
Hong 2003
0/66
8/66
0.8 %
0.05 [ 0.00, 0.92 ]
23/147
36/152
18.8 %
0.60 [ 0.33, 1.07 ]
2/66
7/67
2.4 %
0.27 [ 0.05, 1.34 ]
297
303
24.1 %
0.34 [ 0.14, 0.81 ]
Versiani 2005
Wheatley 1998
Subtotal (95% CI)
Total events: 27 (Mirtazapine), 58 (Others)
Heterogeneity: Tau2 = 0.28; Chi2 = 4.51, df = 3 (P = 0.21); I2 =33%
Test for overall effect: Z = 2.44 (P = 0.015)
3 vs Paroxetine
Benkert 2000
6/139
15/136
6.6 %
0.36 [ 0.14, 0.97 ]
Schatzberg 2002
8/128
24/126
8.9 %
0.28 [ 0.12, 0.66 ]
8/99
30/98
9.0 %
0.20 [ 0.09, 0.46 ]
366
360
24.5 %
0.27 [ 0.16, 0.44 ]
Wade 2003
Subtotal (95% CI)
Total events: 22 (Mirtazapine), 69 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.87, df = 2 (P = 0.65); I2 =0.0%
Test for overall effect: Z = 5.10 (P < 0.00001)
4 vs Sertraline
Behnke 2003
13/176
38/170
14.1 %
0.28 [ 0.14, 0.54 ]
Thase 2000
5/124
17/126
6.0 %
0.27 [ 0.10, 0.75 ]
300
296
20.1 %
0.27 [ 0.16, 0.48 ]
18.2 %
0.29 [ 0.16, 0.53 ]
Subtotal (95% CI)
Total events: 18 (Mirtazapine), 55 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.00, df = 1 (P = 0.96); I2 =0.0%
Test for overall effect: Z = 4.51 (P < 0.00001)
5 vs Fluvoxamine
Schoemaker 2002
17/205
49/207
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
125
(. . .
Study or subgroup
Mirtazapine
Subtotal (95% CI)
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
205
207
18.2 %
0.29 [ 0.16, 0.53 ]
1299
100.0 %
0.33 [ 0.26, 0.43 ]
Total events: 17 (Mirtazapine), 49 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 4.09 (P = 0.000043)
Total (95% CI)
1305
Total events: 98 (Mirtazapine), 258 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 8.91, df = 10 (P = 0.54); I2 =0.0%
Test for overall effect: Z = 8.55 (P < 0.00001)
Test for subgroup differences: Chi2 = 1.64, df = 4 (P = 0.80), I2 =0.0%
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.16. Comparison 2 Mirtazapine versus SSRIs, Outcome 16 Weight gain/Increased appetite.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 16 Weight gain/Increased appetite
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
21/137
6/133
15.2 %
3.83 [ 1.49, 9.82 ]
137
133
15.2 %
3.83 [ 1.49, 9.82 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 21 (Mirtazapine), 6 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.80 (P = 0.0052)
2 vs Fluoxetine
Amini 2005
5/18
2/18
4.2 %
3.08 [ 0.51, 18.53 ]
Hong 2003
9/66
2/66
5.4 %
5.05 [ 1.05, 24.36 ]
10/147
2/152
5.7 %
5.47 [ 1.18, 25.43 ]
8/66
0/67
1.6 %
19.62 [ 1.11, 347.20 ]
297
303
16.9 %
5.23 [ 2.15, 12.76 ]
Versiani 2005
Wheatley 1998
Subtotal (95% CI)
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
126
(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Total events: 32 (Mirtazapine), 6 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.21, df = 3 (P = 0.75); I2 =0.0%
Test for overall effect: Z = 3.64 (P = 0.00027)
3 vs Paroxetine
Benkert 2000
20/139
5/136
13.2 %
4.40 [ 1.60, 12.10 ]
Schatzberg 2002
14/128
0/126
1.7 %
32.04 [ 1.89, 543.20 ]
12/99
7/98
14.1 %
1.79 [ 0.67, 4.77 ]
366
360
28.9 %
3.92 [ 1.19, 12.92 ]
Wade 2003
Subtotal (95% CI)
Total events: 46 (Mirtazapine), 12 (Others)
Heterogeneity: Tau2 = 0.60; Chi2 = 4.76, df = 2 (P = 0.09); I2 =58%
Test for overall effect: Z = 2.24 (P = 0.025)
4 vs Sertraline
Behnke 2003
25/176
3/170
9.1 %
9.22 [ 2.73, 31.14 ]
Thase 2000
31/124
7/126
18.0 %
5.67 [ 2.39, 13.44 ]
300
296
27.1 %
6.67 [ 3.30, 13.49 ]
Subtotal (95% CI)
Total events: 56 (Mirtazapine), 10 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.41, df = 1 (P = 0.52); I2 =0.0%
Test for overall effect: Z = 5.28 (P < 0.00001)
5 vs Fluvoxamine
Schoemaker 2002
12/205
5/207
11.9 %
2.51 [ 0.87, 7.26 ]
205
207
11.9 %
2.51 [ 0.87, 7.26 ]
1299
100.0 %
4.23 [ 2.93, 6.11 ]
Subtotal (95% CI)
Total events: 12 (Mirtazapine), 5 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.70 (P = 0.089)
Total (95% CI)
1305
Total events: 167 (Mirtazapine), 39 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 9.65, df = 10 (P = 0.47); I2 =0.0%
Test for overall effect: Z = 7.71 (P < 0.00001)
Test for subgroup differences: Chi2 = 2.61, df = 4 (P = 0.63), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
127
Analysis 2.17. Comparison 2 Mirtazapine versus SSRIs, Outcome 17 Weight loss/Anorexia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 17 Weight loss/Anorexia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Amini 2005
1/18
3/18
27.1 %
0.29 [ 0.03, 3.14 ]
Hong 2003
0/66
4/66
17.5 %
0.10 [ 0.01, 1.98 ]
Wheatley 1998
2/66
2/67
38.3 %
1.02 [ 0.14, 7.43 ]
150
151
82.8 %
0.42 [ 0.11, 1.62 ]
1 vs Fluoxetine
Subtotal (95% CI)
Total events: 3 (Mirtazapine), 9 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.76, df = 2 (P = 0.41); I2 =0.0%
Test for overall effect: Z = 1.26 (P = 0.21)
2 vs Paroxetine
Benkert 2000
0/139
3/136
17.2 %
0.14 [ 0.01, 2.67 ]
139
136
17.2 %
0.14 [ 0.01, 2.67 ]
289
287
100.0 %
0.35 [ 0.10, 1.18 ]
Subtotal (95% CI)
Total events: 0 (Mirtazapine), 3 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.31 (P = 0.19)
Total (95% CI)
Total events: 3 (Mirtazapine), 12 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.22, df = 3 (P = 0.53); I2 =0.0%
Test for overall effect: Z = 1.69 (P = 0.091)
Test for subgroup differences: Chi2 = 0.45, df = 1 (P = 0.50), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
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Analysis 2.18. Comparison 2 Mirtazapine versus SSRIs, Outcome 18 Sexual dysfunction.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 18 Sexual dysfunction
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
1/18
5/18
12.1 %
0.15 [ 0.02, 1.47 ]
18
18
12.1 %
0.15 [ 0.02, 1.47 ]
4/139
18/136
31.0 %
0.19 [ 0.06, 0.59 ]
139
136
31.0 %
0.19 [ 0.06, 0.59 ]
1 vs Fluoxetine
Amini 2005
Subtotal (95% CI)
Total events: 1 (Mirtazapine), 5 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.62 (P = 0.10)
2 vs Paroxetine
Benkert 2000
Subtotal (95% CI)
Total events: 4 (Mirtazapine), 18 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.89 (P = 0.0038)
3 vs Sertraline
Behnke 2003
2/176
10/170
21.5 %
0.18 [ 0.04, 0.85 ]
Thase 2000
8/124
10/126
35.4 %
0.80 [ 0.30, 2.10 ]
300
296
56.8 %
0.43 [ 0.10, 1.82 ]
100.0 %
0.31 [ 0.13, 0.74 ]
Subtotal (95% CI)
Total events: 10 (Mirtazapine), 20 (Others)
Heterogeneity: Tau2 = 0.68; Chi2 = 2.58, df = 1 (P = 0.11); I2 =61%
Test for overall effect: Z = 1.14 (P = 0.25)
Total (95% CI)
457
450
Total events: 15 (Mirtazapine), 43 (Others)
Heterogeneity: Tau2 = 0.33; Chi2 = 5.14, df = 3 (P = 0.16); I2 =42%
Test for overall effect: Z = 2.62 (P = 0.0087)
Test for subgroup differences: Chi2 = 0.94, df = 2 (P = 0.62), I2 =0.0%
0.02
0.1
Favours Mirtazapine
1
10
50
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
129
Analysis 2.19. Comparison 2 Mirtazapine versus SSRIs, Outcome 19 Anxiety/Agitation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 19 Anxiety/Agitation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
5/139
9/136
24.7 %
0.53 [ 0.17, 1.61 ]
6/99
6/98
23.9 %
0.99 [ 0.31, 3.18 ]
238
234
48.6 %
0.71 [ 0.32, 1.60 ]
1 vs Paroxetine
Benkert 2000
Wade 2003
Subtotal (95% CI)
Total events: 11 (Mirtazapine), 15 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.58, df = 1 (P = 0.44); I2 =0.0%
Test for overall effect: Z = 0.82 (P = 0.41)
2 vs Sertraline
Thase 2000
14/124
9/126
28.8 %
1.65 [ 0.69, 3.98 ]
124
126
28.8 %
1.65 [ 0.69, 3.98 ]
16/205
3/207
22.6 %
5.76 [ 1.65, 20.07 ]
205
207
22.6 %
5.76 [ 1.65, 20.07 ]
567
100.0 %
1.46 [ 0.59, 3.65 ]
Subtotal (95% CI)
Total events: 14 (Mirtazapine), 9 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.13 (P = 0.26)
3 vs Fluvoxamine
Schoemaker 2002
Subtotal (95% CI)
Total events: 16 (Mirtazapine), 3 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.75 (P = 0.0060)
Total (95% CI)
567
Total events: 41 (Mirtazapine), 27 (Others)
Heterogeneity: Tau2 = 0.56; Chi2 = 8.41, df = 3 (P = 0.04); I2 =64%
Test for overall effect: Z = 0.81 (P = 0.42)
Test for subgroup differences: Chi2 = 7.74, df = 2 (P = 0.02), I2 =74%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
130
Analysis 2.20. Comparison 2 Mirtazapine versus SSRIs, Outcome 20 Dizziness/Vertigo/Faintness.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 20 Dizziness/Vertigo/Faintness
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
12/137
6/133
7.5 %
2.03 [ 0.74, 5.58 ]
137
133
7.5 %
2.03 [ 0.74, 5.58 ]
13/66
9/66
8.6 %
1.55 [ 0.61, 3.93 ]
13/147
19/152
12.1 %
0.68 [ 0.32, 1.43 ]
5/66
6/67
5.2 %
0.83 [ 0.24, 2.88 ]
279
285
25.9 %
0.92 [ 0.54, 1.56 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 12 (Mirtazapine), 6 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.38 (P = 0.17)
2 vs Fluoxetine
Hong 2003
Versiani 2005
Wheatley 1998
Subtotal (95% CI)
Total events: 31 (Mirtazapine), 34 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.88, df = 2 (P = 0.39); I2 =0.0%
Test for overall effect: Z = 0.31 (P = 0.75)
3 vs Paroxetine
Benkert 2000
12/139
11/136
9.8 %
1.07 [ 0.46, 2.52 ]
Schatzberg 2002
20/128
18/126
13.5 %
1.11 [ 0.56, 2.22 ]
7/99
15/98
8.3 %
0.42 [ 0.16, 1.08 ]
366
360
31.6 %
0.84 [ 0.47, 1.50 ]
Wade 2003
Subtotal (95% CI)
Total events: 39 (Mirtazapine), 44 (Others)
Heterogeneity: Tau2 = 0.09; Chi2 = 2.98, df = 2 (P = 0.22); I2 =33%
Test for overall effect: Z = 0.58 (P = 0.56)
4 vs Sertraline
Behnke 2003
12/176
17/170
11.5 %
0.66 [ 0.30, 1.42 ]
Thase 2000
14/124
7/126
8.4 %
2.16 [ 0.84, 5.56 ]
300
296
19.8 %
1.16 [ 0.36, 3.70 ]
Subtotal (95% CI)
Total events: 26 (Mirtazapine), 24 (Others)
Heterogeneity: Tau2 = 0.51; Chi2 = 3.66, df = 1 (P = 0.06); I2 =73%
Test for overall effect: Z = 0.24 (P = 0.81)
5 vs Fluvoxamine
Schoemaker 2002
Subtotal (95% CI)
24/205
19/207
15.1 %
1.31 [ 0.69, 2.48 ]
205
207
15.1 %
1.31 [ 0.69, 2.48 ]
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
131
(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
1287
1281
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Total events: 24 (Mirtazapine), 19 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.84 (P = 0.40)
Total (95% CI)
100.0 %
1.04 [ 0.77, 1.41 ]
Total events: 132 (Mirtazapine), 127 (Others)
Heterogeneity: Tau2 = 0.05; Chi2 = 11.52, df = 9 (P = 0.24); I2 =22%
Test for overall effect: Z = 0.27 (P = 0.79)
Test for subgroup differences: Chi2 = 2.93, df = 4 (P = 0.57), I2 =0.0%
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.21. Comparison 2 Mirtazapine versus SSRIs, Outcome 21 Fatigue/Tiredness/Asthenia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 21 Fatigue/Tiredness/Asthenia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
17/137
18/133
15.6 %
0.91 [ 0.44, 1.84 ]
137
133
15.6 %
0.91 [ 0.44, 1.84 ]
4/66
3/67
4.5 %
1.38 [ 0.30, 6.40 ]
66
67
4.5 %
1.38 [ 0.30, 6.40 ]
12/139
11/136
12.0 %
1.07 [ 0.46, 2.52 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 17 (Mirtazapine), 18 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.28 (P = 0.78)
2 vs Fluoxetine
Wheatley 1998
Subtotal (95% CI)
Total events: 4 (Mirtazapine), 3 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.41 (P = 0.68)
3 vs Paroxetine
Benkert 2000
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Study or subgroup
Schatzberg 2002
Wade 2003
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
22/128
15/126
15.7 %
1.54 [ 0.76, 3.12 ]
20/99
7/98
10.9 %
3.29 [ 1.32, 8.19 ]
366
360
38.6 %
1.71 [ 0.94, 3.11 ]
Subtotal (95% CI)
Total events: 54 (Mirtazapine), 33 (Others)
Heterogeneity: Tau2 = 0.11; Chi2 = 3.21, df = 2 (P = 0.20); I2 =38%
Test for overall effect: Z = 1.76 (P = 0.079)
4 vs Sertraline
Behnke 2003
21/176
11/170
14.2 %
1.96 [ 0.91, 4.20 ]
Thase 2000
22/124
9/126
12.8 %
2.80 [ 1.24, 6.36 ]
300
296
27.0 %
2.31 [ 1.32, 4.04 ]
Subtotal (95% CI)
Total events: 43 (Mirtazapine), 20 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.40, df = 1 (P = 0.53); I2 =0.0%
Test for overall effect: Z = 2.94 (P = 0.0032)
5 vs Fluvoxamine
Schoemaker 2002
14/205
15/207
14.4 %
0.94 [ 0.44, 2.00 ]
205
207
14.4 %
0.94 [ 0.44, 2.00 ]
1063
100.0 %
1.53 [ 1.08, 2.15 ]
Subtotal (95% CI)
Total events: 14 (Mirtazapine), 15 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.17 (P = 0.87)
Total (95% CI)
1074
Total events: 132 (Mirtazapine), 89 (Others)
Heterogeneity: Tau2 = 0.07; Chi2 = 9.60, df = 7 (P = 0.21); I2 =27%
Test for overall effect: Z = 2.41 (P = 0.016)
Test for subgroup differences: Chi2 = 5.93, df = 4 (P = 0.20), I2 =33%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
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Analysis 2.22. Comparison 2 Mirtazapine versus SSRIs, Outcome 22 Headache.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 22 Headache
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
13/137
19/133
8.4 %
0.63 [ 0.30, 1.33 ]
137
133
8.4 %
0.63 [ 0.30, 1.33 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 13 (Mirtazapine), 19 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.21 (P = 0.23)
2 vs Fluoxetine
Amini 2005
2/18
4/18
1.4 %
0.44 [ 0.07, 2.76 ]
Hong 2003
5/66
4/66
2.6 %
1.27 [ 0.33, 4.96 ]
28/147
28/152
14.0 %
1.04 [ 0.58, 1.86 ]
6/66
12/67
4.3 %
0.46 [ 0.16, 1.30 ]
297
303
22.3 %
0.86 [ 0.54, 1.36 ]
Versiani 2005
Wheatley 1998
Subtotal (95% CI)
Total events: 41 (Mirtazapine), 48 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.64, df = 3 (P = 0.45); I2 =0.0%
Test for overall effect: Z = 0.64 (P = 0.52)
3 vs Paroxetine
Benkert 2000
13/139
14/136
7.5 %
0.90 [ 0.41, 1.99 ]
Schatzberg 2002
20/128
31/126
12.1 %
0.57 [ 0.30, 1.06 ]
13/99
28/98
8.9 %
0.38 [ 0.18, 0.78 ]
366
360
28.4 %
0.57 [ 0.36, 0.89 ]
Wade 2003
Subtotal (95% CI)
Total events: 46 (Mirtazapine), 73 (Others)
Heterogeneity: Tau2 = 0.03; Chi2 = 2.48, df = 2 (P = 0.29); I2 =19%
Test for overall effect: Z = 2.44 (P = 0.015)
4 vs Sertraline
Behnke 2003
25/176
31/170
14.3 %
0.74 [ 0.42, 1.32 ]
Thase 2000
24/124
36/126
13.6 %
0.60 [ 0.33, 1.08 ]
300
296
27.9 %
0.67 [ 0.44, 1.01 ]
13.0 %
0.84 [ 0.46, 1.53 ]
Subtotal (95% CI)
Total events: 49 (Mirtazapine), 67 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.26, df = 1 (P = 0.61); I2 =0.0%
Test for overall effect: Z = 1.91 (P = 0.056)
5 vs Fluvoxamine
Schoemaker 2002
22/205
26/207
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Study or subgroup
Mirtazapine
Subtotal (95% CI)
Others
Odds Ratio
MH,Random,95%
CI
Continued)
Odds Ratio
MH,Random,95%
CI
Weight
n/N
n/N
205
207
13.0 %
0.84 [ 0.46, 1.53 ]
1299
100.0 %
0.69 [ 0.56, 0.86 ]
Total events: 22 (Mirtazapine), 26 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.58 (P = 0.56)
Total (95% CI)
1305
Total events: 171 (Mirtazapine), 233 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 7.67, df = 10 (P = 0.66); I2 =0.0%
Test for overall effect: Z = 3.34 (P = 0.00085)
Test for subgroup differences: Chi2 = 2.06, df = 4 (P = 0.72), I2 =0.0%
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.23. Comparison 2 Mirtazapine versus SSRIs, Outcome 23 Tremor.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 23 Tremor
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Amini 2005
2/18
4/18
12.9 %
0.44 [ 0.07, 2.76 ]
Hong 2003
2/66
3/66
13.1 %
0.66 [ 0.11, 4.06 ]
3/147
9/152
24.8 %
0.33 [ 0.09, 1.25 ]
231
236
50.8 %
0.42 [ 0.17, 1.07 ]
1 vs Fluoxetine
Versiani 2005
Subtotal (95% CI)
Total events: 7 (Mirtazapine), 16 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.36, df = 2 (P = 0.84); I2 =0.0%
Test for overall effect: Z = 1.81 (P = 0.070)
2 vs Paroxetine
Benkert 2000
1/139
7/136
9.8 %
0.13 [ 0.02, 1.10 ]
Schatzberg 2002
5/128
14/126
39.4 %
0.33 [ 0.11, 0.93 ]
267
262
49.2 %
0.27 [ 0.11, 0.70 ]
Subtotal (95% CI)
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
Odds Ratio
MH,Random,95%
CI
Continued)
Odds Ratio
MH,Random,95%
CI
Weight
Total events: 6 (Mirtazapine), 21 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.56, df = 1 (P = 0.46); I2 =0.0%
Test for overall effect: Z = 2.71 (P = 0.0068)
Total (95% CI)
498
100.0 %
498
0.34 [ 0.18, 0.66 ]
Total events: 13 (Mirtazapine), 37 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.35, df = 4 (P = 0.85); I2 =0.0%
Test for overall effect: Z = 3.19 (P = 0.0014)
Test for subgroup differences: Chi2 = 0.43, df = 1 (P = 0.51), I2 =0.0%
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.24. Comparison 2 Mirtazapine versus SSRIs, Outcome 24 Sleep disturbance.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 24 Sleep disturbance
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
7/147
13/152
19.0 %
0.53 [ 0.21, 1.38 ]
147
152
19.0 %
0.53 [ 0.21, 1.38 ]
15/128
14/126
24.4 %
1.06 [ 0.49, 2.30 ]
5/99
12/98
15.8 %
0.38 [ 0.13, 1.13 ]
227
224
40.2 %
0.68 [ 0.25, 1.85 ]
1 vs Fluoxetine
Versiani 2005
Subtotal (95% CI)
Total events: 7 (Mirtazapine), 13 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.29 (P = 0.20)
2 vs Paroxetine
Schatzberg 2002
Wade 2003
Subtotal (95% CI)
Total events: 20 (Mirtazapine), 26 (Others)
Heterogeneity: Tau2 = 0.30; Chi2 = 2.28, df = 1 (P = 0.13); I2 =56%
Test for overall effect: Z = 0.75 (P = 0.45)
3 vs Sertraline
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Behnke 2003
9/176
15/170
21.7 %
0.56 [ 0.24, 1.31 ]
Thase 2000
6/124
22/126
19.2 %
0.24 [ 0.09, 0.62 ]
300
296
40.9 %
0.37 [ 0.16, 0.85 ]
100.0 %
0.52 [ 0.31, 0.86 ]
Subtotal (95% CI)
Total events: 15 (Mirtazapine), 37 (Others)
Heterogeneity: Tau2 = 0.14; Chi2 = 1.69, df = 1 (P = 0.19); I2 =41%
Test for overall effect: Z = 2.34 (P = 0.020)
Total (95% CI)
674
672
Total events: 42 (Mirtazapine), 76 (Others)
Heterogeneity: Tau2 = 0.12; Chi2 = 6.20, df = 4 (P = 0.18); I2 =35%
Test for overall effect: Z = 2.54 (P = 0.011)
Test for subgroup differences: Chi2 = 0.87, df = 2 (P = 0.65), I2 =0.0%
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 2.25. Comparison 2 Mirtazapine versus SSRIs, Outcome 25 Sleepiness/Drowsiness/Somnolence.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 25 Sleepiness/Drowsiness/Somnolence
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
11/137
8/133
6.6 %
1.36 [ 0.53, 3.51 ]
137
133
6.6 %
1.36 [ 0.53, 3.51 ]
Amini 2005
6/18
2/18
2.2 %
4.00 [ 0.68, 23.41 ]
Hong 2003
8/66
3/66
3.4 %
2.90 [ 0.73, 11.44 ]
20/147
14/152
10.0 %
1.55 [ 0.75, 3.20 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 11 (Mirtazapine), 8 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.64 (P = 0.52)
2 vs Fluoxetine
Versiani 2005
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
137
(. . .
Study or subgroup
Wheatley 1998
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
12/66
12/67
7.3 %
1.02 [ 0.42, 2.47 ]
297
303
22.9 %
1.59 [ 0.97, 2.61 ]
Subtotal (95% CI)
Total events: 46 (Mirtazapine), 31 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.76, df = 3 (P = 0.43); I2 =0.0%
Test for overall effect: Z = 1.82 (P = 0.068)
3 vs Paroxetine
Benkert 2000
15/139
10/136
8.0 %
1.52 [ 0.66, 3.52 ]
Schatzberg 2002
39/128
37/126
14.9 %
1.05 [ 0.62, 1.80 ]
18/99
13/98
9.0 %
1.45 [ 0.67, 3.16 ]
366
360
31.9 %
1.24 [ 0.84, 1.83 ]
Wade 2003
Subtotal (95% CI)
Total events: 72 (Mirtazapine), 60 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.74, df = 2 (P = 0.69); I2 =0.0%
Test for overall effect: Z = 1.08 (P = 0.28)
4 vs Sertraline
Behnke 2003
35/176
13/170
11.0 %
3.00 [ 1.52, 5.89 ]
Thase 2000
33/124
13/126
10.5 %
3.15 [ 1.57, 6.34 ]
300
296
21.5 %
3.07 [ 1.89, 4.99 ]
Subtotal (95% CI)
Total events: 68 (Mirtazapine), 26 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.01, df = 1 (P = 0.92); I2 =0.0%
Test for overall effect: Z = 4.53 (P < 0.00001)
5 vs Fluvoxamine
Schoemaker 2002
Subtotal (95% CI)
63/205
33/207
17.1 %
2.34 [ 1.45, 3.77 ]
205
207
17.1 %
2.34 [ 1.45, 3.77 ]
1299
100.0 %
1.81 [ 1.39, 2.37 ]
Total events: 63 (Mirtazapine), 33 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 3.50 (P = 0.00047)
Total (95% CI)
1305
Total events: 260 (Mirtazapine), 158 (Others)
Heterogeneity: Tau2 = 0.05; Chi2 = 13.42, df = 10 (P = 0.20); I2 =25%
Test for overall effect: Z = 4.36 (P = 0.000013)
Test for subgroup differences: Chi2 = 9.89, df = 4 (P = 0.04), I2 =60%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
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138
Analysis 2.26. Comparison 2 Mirtazapine versus SSRIs, Outcome 26 Suicide attempt.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 26 Suicide attempt
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Behnke 2003
2/176
0/170
100.0 %
4.89 [ 0.23, 102.51 ]
Total (95% CI)
176
170
100.0 %
4.89 [ 0.23, 102.51 ]
1 vs Sertraline
Total events: 2 (Mirtazapine), 0 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.02 (P = 0.31)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
2
Favours Mirtazapine
5
10
Favours Others
Analysis 2.27. Comparison 2 Mirtazapine versus SSRIs, Outcome 27 Subgroup analysis: Response at 2
weeks: Treatment settings: Outpatients in primary care.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 27 Subgroup analysis: Response at 2 weeks: Treatment settings: Outpatients in primary care
Study or subgroup
Mirtazapine
Control
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
22/99
6/98
100.0 %
4.38 [ 1.69, 11.35 ]
99
98
100.0 %
4.38 [ 1.69, 11.35 ]
1 vs Paroxetine
Wade 2003
Total (95% CI)
Total events: 22 (Mirtazapine), 6 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 3.04 (P = 0.0024)
Test for subgroup differences: Not applicable
0.01
0.1
Favours experimental
1
10
100
Favours control
Mirtazapine versus other antidepressive agents for depression (Review)
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139
Analysis 2.28. Comparison 2 Mirtazapine versus SSRIs, Outcome 28 Subgroup analysis: Response at end of
the acute-phase treatment: Treatment settings: Outpatients in primary care.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 28 Subgroup analysis: Response at end of the acute-phase treatment: Treatment settings: Outpatients in primary care
Study or subgroup
Mirtazapine
Control
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
38/99
34/98
100.0 %
1.17 [ 0.66, 2.10 ]
99
98
100.0 %
1.17 [ 0.66, 2.10 ]
1 vs Paroxetine
Wade 2003
Total (95% CI)
Total events: 38 (Mirtazapine), 34 (Control)
Heterogeneity: not applicable
Test for overall effect: Z = 0.54 (P = 0.59)
Test for subgroup differences: Not applicable
0.01
0.1
Favours experimental
1
10
100
Favours control
Mirtazapine versus other antidepressive agents for depression (Review)
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Analysis 2.29. Comparison 2 Mirtazapine versus SSRIs, Outcome 29 Sensitivity analysis: Response at 2
weeks: Studies without imputation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 29 Sensitivity analysis: Response at 2 weeks: Studies without imputation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
21/137
11/133
5.8 %
2.01 [ 0.93, 4.35 ]
137
133
5.8 %
2.01 [ 0.93, 4.35 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 21 (Mirtazapine), 11 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.77 (P = 0.077)
2 vs Fluoxetine
Amini 2005
4/18
3/18
1.2 %
1.43 [ 0.27, 7.55 ]
Hong 2003
20/66
21/66
6.3 %
0.93 [ 0.45, 1.95 ]
31/147
25/152
10.0 %
1.36 [ 0.76, 2.43 ]
16/66
11/67
4.7 %
1.63 [ 0.69, 3.84 ]
297
303
22.3 %
1.27 [ 0.86, 1.88 ]
Versiani 2005
Wheatley 1998
Subtotal (95% CI)
Total events: 71 (Mirtazapine), 60 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 1.07, df = 3 (P = 0.78); I2 =0.0%
Test for overall effect: Z = 1.20 (P = 0.23)
3 vs Paroxetine
Benkert 2000
40/139
27/136
10.9 %
1.63 [ 0.93, 2.85 ]
Schatzberg 2002
35/128
16/126
8.0 %
2.59 [ 1.35, 4.97 ]
22/99
6/98
3.8 %
4.38 [ 1.69, 11.35 ]
366
360
22.8 %
2.39 [ 1.42, 4.02 ]
Wade 2003
Subtotal (95% CI)
Total events: 97 (Mirtazapine), 49 (Others)
Heterogeneity: Tau2 = 0.08; Chi2 = 3.34, df = 2 (P = 0.19); I2 =40%
Test for overall effect: Z = 3.29 (P = 0.0010)
4 vs Sertraline
Behnke 2003
83/176
62/170
18.3 %
1.55 [ 1.01, 2.39 ]
Thase 2000
47/124
40/126
12.5 %
1.31 [ 0.78, 2.21 ]
300
296
30.8 %
1.45 [ 1.04, 2.02 ]
Subtotal (95% CI)
Total events: 130 (Mirtazapine), 102 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.24, df = 1 (P = 0.62); I2 =0.0%
Test for overall effect: Z = 2.20 (P = 0.028)
5 vs Fluvoxamine
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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(. . .
Mirtazapine
n/N
n/N
Schoemaker 2002
65/205
52/207
18.3 %
1.38 [ 0.90, 2.13 ]
205
207
18.3 %
1.38 [ 0.90, 2.13 ]
1299
100.0 %
1.58 [ 1.31, 1.90 ]
Subtotal (95% CI)
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
Study or subgroup
Total events: 65 (Mirtazapine), 52 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.48 (P = 0.14)
Total (95% CI)
1305
Total events: 384 (Mirtazapine), 274 (Others)
Heterogeneity: Tau2 = 0.00; Chi2 = 10.10, df = 10 (P = 0.43); I2 =1%
Test for overall effect: Z = 4.79 (P < 0.00001)
Test for subgroup differences: Chi2 = 4.46, df = 4 (P = 0.35), I2 =10%
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 2.30. Comparison 2 Mirtazapine versus SSRIs, Outcome 30 Sensitivity analysis: Response at end of
the acute-phase treatment: Studies without imputation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 2 Mirtazapine versus SSRIs
Outcome: 30 Sensitivity analysis: Response at end of the acute-phase treatment: Studies without imputation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
116/137
117/133
5.4 %
0.76 [ 0.38, 1.52 ]
137
133
5.4 %
0.76 [ 0.38, 1.52 ]
1 vs Citalolpram
Leinonen 1999
Subtotal (95% CI)
Total events: 116 (Mirtazapine), 117 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.79 (P = 0.43)
2 vs Fluoxetine
Amini 2005
12/18
8/18
1.5 %
2.50 [ 0.65, 9.65 ]
Hong 2003
35/66
30/66
5.7 %
1.35 [ 0.68, 2.69 ]
106/147
104/152
10.7 %
1.19 [ 0.73, 1.96 ]
Versiani 2005
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
142
(. . .
Study or subgroup
Wheatley 1998
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Continued)
Odds Ratio
MH,Random,95%
CI
n/N
n/N
39/66
28/67
5.6 %
2.01 [ 1.01, 4.01 ]
297
303
23.4 %
1.46 [ 1.04, 2.04 ]
Subtotal (95% CI)
Total events: 192 (Mirtazapine), 170 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 2.12, df = 3 (P = 0.55); I2 =0.0%
Test for overall effect: Z = 2.20 (P = 0.028)
3 vs Paroxetine
Benkert 2000
74/139
66/136
11.8 %
1.21 [ 0.75, 1.94 ]
Schatzberg 2002
72/128
60/126
10.9 %
1.41 [ 0.86, 2.32 ]
38/99
34/98
7.9 %
1.17 [ 0.66, 2.10 ]
366
360
30.6 %
1.27 [ 0.94, 1.70 ]
Wade 2003
Subtotal (95% CI)
Total events: 184 (Mirtazapine), 160 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.30, df = 2 (P = 0.86); I2 =0.0%
Test for overall effect: Z = 1.58 (P = 0.11)
4 vs Sertraline
Behnke 2003
117/176
114/170
13.2 %
0.97 [ 0.62, 1.52 ]
Thase 2000
61/124
63/126
10.8 %
0.97 [ 0.59, 1.59 ]
300
296
24.0 %
0.97 [ 0.70, 1.35 ]
Subtotal (95% CI)
Total events: 178 (Mirtazapine), 177 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.00, df = 1 (P = 0.99); I2 =0.0%
Test for overall effect: Z = 0.17 (P = 0.86)
5 vs Fluvoxamine
Schoemaker 2002
132/205
127/207
16.6 %
1.14 [ 0.76, 1.70 ]
205
207
16.6 %
1.14 [ 0.76, 1.70 ]
1299
100.0 %
1.17 [ 1.00, 1.38 ]
Subtotal (95% CI)
Total events: 132 (Mirtazapine), 127 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.64 (P = 0.52)
Total (95% CI)
1305
Total events: 802 (Mirtazapine), 751 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 7.07, df = 10 (P = 0.72); I2 =0.0%
Test for overall effect: Z = 1.93 (P = 0.054)
Test for subgroup differences: Chi2 = 4.66, df = 4 (P = 0.32), I2 =14%
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
143
Analysis 2.31. Comparison 2 Mirtazapine versus SSRIs, Outcome 31 Secondary outcome (SKEWED DATA:
depression severity) at 2 weeks.
Secondary outcome (SKEWED DATA: depression severity) at 2 weeks
Study
Comparator drug
Measurement
Mirtazapine: mean
SD
N
Comparator:
mean
SD
N
Schoemaker
2002
Fluvoxamine
HAMD17
-9.2
5.86
199
-7.3
6.11
203
Winokur
2003
Fluoxetine
HAMD21
16.1
5.7
8
18.0
9.6
11
note
Analysis 2.32. Comparison 2 Mirtazapine versus SSRIs, Outcome 32 Secondary outcome (SKEWED DATA:
depression severity) at end of the acute-phase treatment.
Secondary outcome (SKEWED DATA: depression severity) at end of the acute-phase treatment
Study
Comparator drug
Measurement
Mirtazapine: mean
SD
N
Comparator:
mean
SD
N
Schoemaker
2002
Fluvoxamine
HAMD17
-14.3
7.33
199
-13.7
7.68
203
Thase
2000
Sertraline
HAMD17
8.7
7.6
119
10.5
7.2
124
Winokur
2003
Fluoxetine
HAMD21
7.1
3.7
8
12.2
9.2
11
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
note
144
Analysis 3.1. Comparison 3 Mirtazapine versus SNRIs, Outcome 1 Primary outcome (response) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 1 Primary outcome (response) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
40/130
18/128
53.0 %
2.72 [ 1.46, 5.06 ]
34/78
23/79
47.0 %
1.88 [ 0.97, 3.64 ]
208
207
100.0 %
2.29 [ 1.45, 3.59 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 74 (Mirtazapine), 41 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.63, df = 1 (P = 0.43); I2 =0.0%
Test for overall effect: Z = 3.58 (P = 0.00035)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 3.2. Comparison 3 Mirtazapine versus SNRIs, Outcome 2 Primary outcome (response) at end of
the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 2 Primary outcome (response) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
65/130
52/128
62.4 %
1.46 [ 0.89, 2.39 ]
48/78
39/79
37.6 %
1.64 [ 0.87, 3.10 ]
208
207
100.0 %
1.53 [ 1.03, 2.25 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 113 (Mirtazapine), 91 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.08, df = 1 (P = 0.78); I2 =0.0%
Test for overall effect: Z = 2.13 (P = 0.033)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
145
Analysis 3.3. Comparison 3 Mirtazapine versus SNRIs, Outcome 3 Secondary outcome (remission) at 2
weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 3 Secondary outcome (remission) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
22/130
8/128
69.2 %
3.06 [ 1.31, 7.15 ]
5/78
4/79
30.8 %
1.28 [ 0.33, 4.97 ]
208
207
100.0 %
2.34 [ 1.07, 5.13 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 27 (Mirtazapine), 12 (Others)
Heterogeneity: Tau2 = 0.04; Chi2 = 1.13, df = 1 (P = 0.29); I2 =12%
Test for overall effect: Z = 2.12 (P = 0.034)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
146
Analysis 3.4. Comparison 3 Mirtazapine versus SNRIs, Outcome 4 Secondary outcome (remission) at end
of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 4 Secondary outcome (remission) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
28/130
19/128
52.3 %
1.57 [ 0.83, 2.99 ]
29/78
22/79
47.7 %
1.53 [ 0.78, 3.01 ]
208
207
100.0 %
1.55 [ 0.98, 2.47 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 57 (Mirtazapine), 41 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.00, df = 1 (P = 0.96); I2 =0.0%
Test for overall effect: Z = 1.86 (P = 0.063)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
147
Analysis 3.5. Comparison 3 Mirtazapine versus SNRIs, Outcome 5 Secondary outcome (withdrawal due to
any reason).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 5 Secondary outcome (withdrawal due to any reason)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
39/130
47/128
64.3 %
0.74 [ 0.44, 1.24 ]
18/78
29/79
35.7 %
0.52 [ 0.26, 1.04 ]
208
207
100.0 %
0.65 [ 0.43, 0.99 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 57 (Mirtazapine), 76 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.64, df = 1 (P = 0.42); I2 =0.0%
Test for overall effect: Z = 2.02 (P = 0.043)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
148
Analysis 3.6. Comparison 3 Mirtazapine versus SNRIs, Outcome 6 Secondary outcome (withdrawal due to
adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 6 Secondary outcome (withdrawal due to adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
23/130
29/128
66.7 %
0.73 [ 0.40, 1.35 ]
4/78
12/79
33.3 %
0.30 [ 0.09, 0.98 ]
208
207
100.0 %
0.55 [ 0.24, 1.24 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 27 (Mirtazapine), 41 (Others)
Heterogeneity: Tau2 = 0.17; Chi2 = 1.72, df = 1 (P = 0.19); I2 =42%
Test for overall effect: Z = 1.44 (P = 0.15)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 3.7. Comparison 3 Mirtazapine versus SNRIs, Outcome 7 Secondary outcome (having some
adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 7 Secondary outcome (having some adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
58/78
52/79
100.0 %
1.51 [ 0.76, 3.00 ]
78
79
100.0 %
1.51 [ 0.76, 3.00 ]
1 vs Venlafaxine
Guelfi 2000
Total (95% CI)
Total events: 58 (Mirtazapine), 52 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.16 (P = 0.24)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
149
Analysis 3.8. Comparison 3 Mirtazapine versus SNRIs, Outcome 8 Hypotension/Bradycardia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 8 Hypotension/Bradycardia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
1/78
5/79
100.0 %
0.19 [ 0.02, 1.68 ]
78
79
100.0 %
0.19 [ 0.02, 1.68 ]
1 vs Venlafaxine
Guelfi 2000
Total (95% CI)
Total events: 1 (Mirtazapine), 5 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.49 (P = 0.14)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
150
Analysis 3.9. Comparison 3 Mirtazapine versus SNRIs, Outcome 9 Sweating.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 9 Sweating
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
0/78
15/79
100.0 %
0.03 [ 0.00, 0.45 ]
78
79
100.0 %
0.03 [ 0.00, 0.45 ]
1 vs Venlafaxine
Guelfi 2000
Total (95% CI)
Total events: 0 (Mirtazapine), 15 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.51 (P = 0.012)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 3.10. Comparison 3 Mirtazapine versus SNRIs, Outcome 10 Constipation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 10 Constipation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
3/78
12/79
100.0 %
0.22 [ 0.06, 0.83 ]
78
79
100.0 %
0.22 [ 0.06, 0.83 ]
1 vs Venlafaxine
Guelfi 2000
Total (95% CI)
Total events: 3 (Mirtazapine), 12 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.25 (P = 0.025)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
151
Analysis 3.11. Comparison 3 Mirtazapine versus SNRIs, Outcome 11 Dry mouth/Decreased salivation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 11 Dry mouth/Decreased salivation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
19/130
0/128
42.8 %
44.95 [ 2.68, 752.97 ]
7/78
3/79
57.2 %
2.50 [ 0.62, 10.03 ]
208
207
100.0 %
8.61 [ 0.35, 211.85 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 26 (Mirtazapine), 3 (Others)
Heterogeneity: Tau2 = 4.17; Chi2 = 4.24, df = 1 (P = 0.04); I2 =76%
Test for overall effect: Z = 1.32 (P = 0.19)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 3.12. Comparison 3 Mirtazapine versus SNRIs, Outcome 12 Nausea/Vomiting/Gastric distress.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 12 Nausea/Vomiting/Gastric distress
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
0/130
27/128
45.9 %
0.01 [ 0.00, 0.23 ]
5/78
8/79
54.1 %
0.61 [ 0.19, 1.95 ]
208
207
100.0 %
0.11 [ 0.00, 9.34 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 5 (Mirtazapine), 35 (Others)
Heterogeneity: Tau2 = 9.22; Chi2 = 8.66, df = 1 (P = 0.003); I2 =88%
Test for overall effect: Z = 0.98 (P = 0.33)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
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152
Analysis 3.13. Comparison 3 Mirtazapine versus SNRIs, Outcome 13 Anxiety/Agitation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 13 Anxiety/Agitation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
4/78
4/79
100.0 %
1.01 [ 0.24, 4.20 ]
78
79
100.0 %
1.01 [ 0.24, 4.20 ]
1 vs Venlafaxine
Guelfi 2000
Total (95% CI)
Total events: 4 (Mirtazapine), 4 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.02 (P = 0.99)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
153
Analysis 3.14. Comparison 3 Mirtazapine versus SNRIs, Outcome 14 Fatigue/Tiredness/Asthenia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 14 Fatigue/Tiredness/Asthenia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
37/130
18/128
100.0 %
2.43 [ 1.30, 4.55 ]
130
128
100.0 %
2.43 [ 1.30, 4.55 ]
1 vs Venlafaxine
Benkert 2006
Total (95% CI)
Total events: 37 (Mirtazapine), 18 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.78 (P = 0.0055)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 3.15. Comparison 3 Mirtazapine versus SNRIs, Outcome 15 Headache.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 15 Headache
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
19/130
17/128
70.3 %
1.12 [ 0.55, 2.26 ]
6/78
9/79
29.7 %
0.65 [ 0.22, 1.92 ]
208
207
100.0 %
0.95 [ 0.53, 1.72 ]
1 vs Venlafaxine
Benkert 2006
Guelfi 2000
Total (95% CI)
Total events: 25 (Mirtazapine), 26 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.68, df = 1 (P = 0.41); I2 =0.0%
Test for overall effect: Z = 0.17 (P = 0.87)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
154
Analysis 3.16. Comparison 3 Mirtazapine versus SNRIs, Outcome 16 Sleep disturbance.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 16 Sleep disturbance
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Benkert 2006
0/130
17/128
100.0 %
0.02 [ 0.00, 0.41 ]
Total (95% CI)
130
128
100.0 %
0.02 [ 0.00, 0.41 ]
1 vs Venlafaxine
Total events: 0 (Mirtazapine), 17 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.58 (P = 0.0099)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 3.17. Comparison 3 Mirtazapine versus SNRIs, Outcome 17 Sleepiness/Drowsiness/Somnolence.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 17 Sleepiness/Drowsiness/Somnolence
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
6/78
4/79
100.0 %
1.56 [ 0.42, 5.77 ]
78
79
100.0 %
1.56 [ 0.42, 5.77 ]
1 vs Venlafaxine
Guelfi 2000
Total (95% CI)
Total events: 6 (Mirtazapine), 4 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.67 (P = 0.50)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
155
Analysis 3.18. Comparison 3 Mirtazapine versus SNRIs, Outcome 18 Completed suicide.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 3 Mirtazapine versus SNRIs
Outcome: 18 Completed suicide
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
0/78
1/79
100.0 %
0.33 [ 0.01, 8.31 ]
78
79
100.0 %
0.33 [ 0.01, 8.31 ]
1 vs Venlafaxine
Guelfi 2000
Total (95% CI)
Total events: 0 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.67 (P = 0.50)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 4.1. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 1 Primary outcome
(response) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 1 Primary outcome (response) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
13/50
12/50
41.1 %
1.11 [ 0.45, 2.75 ]
17/100
15/100
58.9 %
1.16 [ 0.54, 2.48 ]
150
150
100.0 %
1.14 [ 0.64, 2.04 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 30 (Mirtazapine), 27 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.00, df = 1 (P = 0.94); I2 =0.0%
Test for overall effect: Z = 0.44 (P = 0.66)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
156
Analysis 4.2. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 2 Primary outcome
(response) at end of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 2 Primary outcome (response) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
25/50
20/50
33.4 %
1.50 [ 0.68, 3.31 ]
61/100
51/100
66.6 %
1.50 [ 0.86, 2.63 ]
150
150
100.0 %
1.50 [ 0.95, 2.37 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 86 (Mirtazapine), 71 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.00, df = 1 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 1.74 (P = 0.082)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
157
Analysis 4.3. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 3 Secondary
outcome (remission) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 3 Secondary outcome (remission) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
6/50
6/50
72.9 %
1.00 [ 0.30, 3.34 ]
2/100
2/100
27.1 %
1.00 [ 0.14, 7.24 ]
150
150
100.0 %
1.00 [ 0.36, 2.80 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 8 (Mirtazapine), 8 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.0, df = 1 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 0.0 (P = 1.0)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
158
Analysis 4.4. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 4 Secondary
outcome (remission) at end of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 4 Secondary outcome (remission) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
13/50
9/50
39.1 %
1.60 [ 0.61, 4.18 ]
17/100
14/100
60.9 %
1.26 [ 0.58, 2.71 ]
150
150
100.0 %
1.38 [ 0.76, 2.52 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 30 (Mirtazapine), 23 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.15, df = 1 (P = 0.70); I2 =0.0%
Test for overall effect: Z = 1.06 (P = 0.29)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
159
Analysis 4.5. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 5 Secondary
outcome (withdrawal due to any reason).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 5 Secondary outcome (withdrawal due to any reason)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
11/50
16/50
39.0 %
0.60 [ 0.24, 1.47 ]
26/100
23/100
61.0 %
1.18 [ 0.62, 2.24 ]
150
150
100.0 %
0.90 [ 0.47, 1.72 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 37 (Mirtazapine), 39 (Others)
Heterogeneity: Tau2 = 0.07; Chi2 = 1.43, df = 1 (P = 0.23); I2 =30%
Test for overall effect: Z = 0.31 (P = 0.76)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
160
Analysis 4.6. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 6 Secondary
outcome (withdrawal due to adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 6 Secondary outcome (withdrawal due to adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
7/50
9/50
70.5 %
0.74 [ 0.25, 2.18 ]
2/100
5/100
29.5 %
0.39 [ 0.07, 2.05 ]
150
150
100.0 %
0.61 [ 0.25, 1.51 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 9 (Mirtazapine), 14 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.41, df = 1 (P = 0.52); I2 =0.0%
Test for overall effect: Z = 1.06 (P = 0.29)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 4.7. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 7
Hypertension/Tachycardia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 7 Hypertension/Tachycardia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Halikas 1995
2/50
6/50
100.0 %
0.31 [ 0.06, 1.59 ]
Total (95% CI)
50
50
100.0 %
0.31 [ 0.06, 1.59 ]
1 vs Trazodone
Total events: 2 (Mirtazapine), 6 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.41 (P = 0.16)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
161
Analysis 4.8. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 8
Hypotension/Bradycardia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 8 Hypotension/Bradycardia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
1/50
7/50
69.4 %
0.13 [ 0.01, 1.06 ]
0/100
1/100
30.6 %
0.33 [ 0.01, 8.20 ]
150
150
100.0 %
0.17 [ 0.03, 1.00 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 1 (Mirtazapine), 8 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.24, df = 1 (P = 0.62); I2 =0.0%
Test for overall effect: Z = 1.96 (P = 0.050)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
162
Analysis 4.9. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 9 Constipation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 9 Constipation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Halikas 1995
9/50
12/50
100.0 %
0.70 [ 0.26, 1.83 ]
Total (95% CI)
50
50
100.0 %
0.70 [ 0.26, 1.83 ]
1 vs Trazodone
Total events: 9 (Mirtazapine), 12 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.73 (P = 0.46)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 4.10. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 10 Dry
mouth/Decreased salivation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 10 Dry mouth/Decreased salivation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Halikas 1995
24/50
31/50
73.4 %
0.57 [ 0.26, 1.25 ]
van Moffaert 1995
1/100
7/100
26.6 %
0.13 [ 0.02, 1.11 ]
150
150
100.0 %
0.39 [ 0.11, 1.37 ]
1 vs Trazodone
Total (95% CI)
Total events: 25 (Mirtazapine), 38 (Others)
Heterogeneity: Tau2 = 0.40; Chi2 = 1.60, df = 1 (P = 0.21); I2 =38%
Test for overall effect: Z = 1.48 (P = 0.14)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
163
Analysis 4.11. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 11
Nausea/Vomiting/Gastric distress.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 11 Nausea/Vomiting/Gastric distress
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Halikas 1995
5/50
7/50
100.0 %
0.68 [ 0.20, 2.32 ]
Total (95% CI)
50
50
100.0 %
0.68 [ 0.20, 2.32 ]
1 vs Trazodone
Total events: 5 (Mirtazapine), 7 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.61 (P = 0.54)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
164
Analysis 4.12. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 12 Weight
gain/Increased appetite.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 12 Weight gain/Increased appetite
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
12/50
3/50
100.0 %
4.95 [ 1.30, 18.81 ]
50
50
100.0 %
4.95 [ 1.30, 18.81 ]
1 vs Trazodone
Halikas 1995
Total (95% CI)
Total events: 12 (Mirtazapine), 3 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 2.35 (P = 0.019)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 4.13. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 13 Weight
loss/Anorexia.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 13 Weight loss/Anorexia
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Halikas 1995
0/50
1/50
100.0 %
0.33 [ 0.01, 8.21 ]
Total (95% CI)
50
50
100.0 %
0.33 [ 0.01, 8.21 ]
1 vs Trazodone
Total events: 0 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.68 (P = 0.50)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
165
Analysis 4.14. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 14
Anxiety/Agitation.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 14 Anxiety/Agitation
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
2/50
2/50
33.3 %
1.00 [ 0.14, 7.39 ]
3/100
6/100
66.7 %
0.48 [ 0.12, 1.99 ]
150
150
100.0 %
0.62 [ 0.19, 1.96 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 5 (Mirtazapine), 8 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.34, df = 1 (P = 0.56); I2 =0.0%
Test for overall effect: Z = 0.82 (P = 0.41)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
166
Analysis 4.15. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 15
Dizziness/Vertigo/Faintness.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 15 Dizziness/Vertigo/Faintness
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Halikas 1995
11/50
14/50
70.7 %
0.73 [ 0.29, 1.80 ]
van Moffaert 1995
3/100
6/100
29.3 %
0.48 [ 0.12, 1.99 ]
150
150
100.0 %
0.64 [ 0.30, 1.39 ]
1 vs Trazodone
Total (95% CI)
Total events: 14 (Mirtazapine), 20 (Others)
Heterogeneity: Tau2 = 0.0; Chi2 = 0.22, df = 1 (P = 0.64); I2 =0.0%
Test for overall effect: Z = 1.12 (P = 0.26)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 4.16. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 16 Headache.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 16 Headache
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Halikas 1995
7/50
10/50
100.0 %
0.65 [ 0.23, 1.87 ]
Total (95% CI)
50
50
100.0 %
0.65 [ 0.23, 1.87 ]
1 vs Trazodone
Total events: 7 (Mirtazapine), 10 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.80 (P = 0.43)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
167
Analysis 4.17. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 17 Sleep
disturbance.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 17 Sleep disturbance
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
4/100
9/100
100.0 %
0.42 [ 0.13, 1.42 ]
100
100
100.0 %
0.42 [ 0.13, 1.42 ]
1 vs Trazodone
van Moffaert 1995
Total (95% CI)
Total events: 4 (Mirtazapine), 9 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 1.40 (P = 0.16)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
168
Analysis 4.18. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 18
Sleepiness/Drowsiness/Somnolence.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 18 Sleepiness/Drowsiness/Somnolence
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
27/50
28/50
50.8 %
0.92 [ 0.42, 2.03 ]
10/100
21/100
49.2 %
0.42 [ 0.19, 0.94 ]
150
150
100.0 %
0.62 [ 0.29, 1.36 ]
1 vs Trazodone
Halikas 1995
van Moffaert 1995
Total (95% CI)
Total events: 37 (Mirtazapine), 49 (Others)
Heterogeneity: Tau2 = 0.15; Chi2 = 1.88, df = 1 (P = 0.17); I2 =47%
Test for overall effect: Z = 1.19 (P = 0.23)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Mirtazapine
2
5
10
Favours Others
Analysis 4.19. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 19 Completed
suicide.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 19 Completed suicide
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
1/100
0/100
100.0 %
3.03 [ 0.12, 75.28 ]
100
100
100.0 %
3.03 [ 0.12, 75.28 ]
1 vs Trazodone
van Moffaert 1995
Total (95% CI)
Total events: 1 (Mirtazapine), 0 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.68 (P = 0.50)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
169
Analysis 4.20. Comparison 4 Mirtazapine versus heterocyclic antidepressants, Outcome 20 Suicide attempt.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 4 Mirtazapine versus heterocyclic antidepressants
Outcome: 20 Suicide attempt
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
2/100
1/100
100.0 %
2.02 [ 0.18, 22.65 ]
100
100
100.0 %
2.02 [ 0.18, 22.65 ]
1 vs Trazodone
van Moffaert 1995
Total (95% CI)
Total events: 2 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.57 (P = 0.57)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
170
Analysis 5.1. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 1 Primary outcome
(response) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 5 Mirtazapine versus newer antidepressants
Outcome: 1 Primary outcome (response) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
3/20
3/20
100.0 %
1.00 [ 0.18, 5.67 ]
20
20
100.0 %
1.00 [ 0.18, 5.67 ]
1 vs Reboxetine
Schule 2006
Total (95% CI)
Total events: 3 (Mirtazapine), 3 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 5.2. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 2 Primary outcome
(response) at end of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 5 Mirtazapine versus newer antidepressants
Outcome: 2 Primary outcome (response) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
13/20
13/20
100.0 %
1.00 [ 0.27, 3.67 ]
20
20
100.0 %
1.00 [ 0.27, 3.67 ]
1 vs Reboxetine
Schule 2006
Total (95% CI)
Total events: 13 (Mirtazapine), 13 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
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171
Analysis 5.3. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 3 Secondary outcome
(remission) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 5 Mirtazapine versus newer antidepressants
Outcome: 3 Secondary outcome (remission) at 2 weeks
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
1/20
1/20
100.0 %
1.00 [ 0.06, 17.18 ]
20
20
100.0 %
1.00 [ 0.06, 17.18 ]
1 vs Reboxetine
Schule 2006
Total (95% CI)
Total events: 1 (Mirtazapine), 1 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
1
Favours Others
2
5
10
Favours Mirtazapine
Analysis 5.4. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 4 Secondary outcome
(remission) at end of the acute-phase treatment.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 5 Mirtazapine versus newer antidepressants
Outcome: 4 Secondary outcome (remission) at end of the acute-phase treatment
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
7/20
6/20
100.0 %
1.26 [ 0.33, 4.73 ]
20
20
100.0 %
1.26 [ 0.33, 4.73 ]
1 vs Reboxetine
Schule 2006
Total (95% CI)
Total events: 7 (Mirtazapine), 6 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.34 (P = 0.74)
Test for subgroup differences: Not applicable
0.1 0.2
0.5
Favours Others
1
2
5
10
Favours Mirtazapine
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172
Analysis 5.5. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 5 Secondary outcome
(depression severity) at 2 weeks.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 5 Mirtazapine versus newer antidepressants
Outcome: 5 Secondary outcome (depression severity) at 2 weeks
Study or subgroup
Mirtazapine
Std.
Mean
Difference
Control
N
Mean(SD)
N
Mean(SD)
20
15.27 (7.44)
20
17.7 (5.05)
Weight
IV,Random,95% CI
Std.
Mean
Difference
IV,Random,95% CI
1 vs Reboxetine
Schule 2006
Total (95% CI)
20
20
100.0 %
-0.37 [ -1.00, 0.25 ]
100.0 %
-0.37 [ -1.00, 0.25 ]
Heterogeneity: not applicable
Test for overall effect: Z = 1.17 (P = 0.24)
Test for subgroup differences: Not applicable
-4
-2
0
2
Favours mirtazapine
4
Favours control
Analysis 5.6. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 6 Secondary outcome
(withdrawal due to any reason).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 5 Mirtazapine versus newer antidepressants
Outcome: 6 Secondary outcome (withdrawal due to any reason)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Brunnauer 2008
0/20
0/20
Not estimable
Schule 2006
0/20
0/20
Not estimable
40
40
Not estimable
1 vs Reboxetine
Total (95% CI)
Total events: 0 (Mirtazapine), 0 (Others)
Heterogeneity: not applicable
Test for overall effect: not applicable
Test for subgroup differences: Chi2 = 0.0, df = -1 (P = 0.0), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
173
Analysis 5.7. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 7 Secondary outcome
(withdrawal due to adverse events).
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 5 Mirtazapine versus newer antidepressants
Outcome: 7 Secondary outcome (withdrawal due to adverse events)
Study or subgroup
Mirtazapine
Others
Odds Ratio
MH,Random,95%
CI
Weight
Odds Ratio
MH,Random,95%
CI
n/N
n/N
Brunnauer 2008
0/20
0/20
Not estimable
Schule 2006
0/20
0/20
Not estimable
40
40
Not estimable
1 vs Reboxetine
Total (95% CI)
Total events: 0 (Mirtazapine), 0 (Others)
Heterogeneity: not applicable
Test for overall effect: not applicable
Test for subgroup differences: Chi2 = 0.0, df = -1 (P = 0.0), I2 =0.0%
0.1 0.2
0.5
Favours Mirtazapine
1
2
5
10
Favours Others
Analysis 5.8. Comparison 5 Mirtazapine versus newer antidepressants, Outcome 8 Secondary outcome
(SKEWED DATA: depression severity) at end of the acute-phase treatment.
Secondary outcome (SKEWED DATA: depression severity) at end of the acute-phase treatment
Study
Comparator drug
Measurement
Mirtazapine: mean
SD
N
Comparator:
mean
SD
N
Schule
2006
Reboxetine
21-item
HAM-D
10.87
6.91
20
11.17
6.17
20
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
note
174
Analysis 6.1. Comparison 6 Funnel plot analysis: primary outcome (response) at end of the acute-phase
treatment, Outcome 1 vs all compounds.
Review:
Mirtazapine versus other antidepressive agents for depression
Comparison: 6 Funnel plot analysis: primary outcome (response) at end of the acute-phase treatment
Outcome: 1 vs all compounds
Study or subgroup
Mirtazapine
Others
n/N
n/N
Risk Ratio
Weight
Bremner 1995
31/50
24/50
1.8 %
1.29 [ 0.80, 2.08 ]
Hoyberg 1996
25/56
34/59
2.4 %
0.77 [ 0.48, 1.25 ]
Mullin 1996
38/79
41/77
3.1 %
0.90 [ 0.60, 1.36 ]
53/103
62/104
4.5 %
0.86 [ 0.63, 1.19 ]
Smith 1990
25/50
26/50
1.9 %
0.96 [ 0.58, 1.59 ]
Zivkov 1995
81/125
80/126
5.9 %
1.02 [ 0.80, 1.30 ]
463
466
19.6 %
0.95 [ 0.82, 1.11 ]
59/87
61/87
4.5 %
0.97 [ 0.74, 1.26 ]
87
87
4.5 %
0.97 [ 0.74, 1.26 ]
54/83
55/80
4.1 %
0.95 [ 0.71, 1.26 ]
83
80
4.1 %
0.95 [ 0.71, 1.26 ]
38/114
43/121
3.1 %
0.94 [ 0.59, 1.49 ]
114
121
3.1 %
0.94 [ 0.59, 1.49 ]
116/137
117/133
8.7 %
0.96 [ 0.85, 1.09 ]
137
133
8.7 %
0.96 [ 0.85, 1.09 ]
M-H,Fixed,99% CI
Risk Ratio
M-H,Fixed,99% CI
1 vs Amitriptyline
Organon 85146
Subtotal (99% CI)
Total events: 253 (Mirtazapine), 267 (Others)
Heterogeneity: Chi2 = 5.23, df = 5 (P = 0.39); I2 =4%
Test for overall effect: Z = 0.81 (P = 0.42)
2 vs Clomipramine
Richou 1995
Subtotal (99% CI)
Total events: 59 (Mirtazapine), 61 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.33 (P = 0.74)
3 vs Doxepin
Marttila 1995
Subtotal (99% CI)
Total events: 54 (Mirtazapine), 55 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.50 (P = 0.62)
4 vs Nortriptyline
Fava 2006
Subtotal (99% CI)
Total events: 38 (Mirtazapine), 43 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.35 (P = 0.72)
5 vs Citalolpram
Leinonen 1999
Subtotal (99% CI)
0.1 0.2
0.5
Favours others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
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Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
175
(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
Risk Ratio
Weight
M-H,Fixed,99% CI
Continued)
Risk Ratio
M-H,Fixed,99% CI
Total events: 116 (Mirtazapine), 117 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.79 (P = 0.43)
6 vs Fluoxetine
Amini 2005
12/18
8/18
0.6 %
1.50 [ 0.67, 3.35 ]
Hong 2003
35/66
30/66
2.2 %
1.17 [ 0.74, 1.84 ]
106/147
104/152
7.5 %
1.05 [ 0.87, 1.28 ]
39/66
28/67
2.0 %
1.41 [ 0.90, 2.23 ]
8/9
6/13
0.4 %
1.93 [ 0.84, 4.41 ]
306
316
12.7 %
1.18 [ 1.00, 1.39 ]
Versiani 2005
Wheatley 1998
Winokur 2003
Subtotal (99% CI)
Total events: 200 (Mirtazapine), 176 (Others)
Heterogeneity: Chi2 = 6.17, df = 4 (P = 0.19); I2 =35%
Test for overall effect: Z = 2.54 (P = 0.011)
7 vs Paroxetine
Benkert 2000
74/139
66/136
4.9 %
1.10 [ 0.81, 1.49 ]
Schatzberg 2002
72/128
60/126
4.5 %
1.18 [ 0.86, 1.62 ]
38/99
34/98
2.5 %
1.11 [ 0.68, 1.80 ]
366
360
11.9 %
1.13 [ 0.93, 1.38 ]
Wade 2003
Subtotal (99% CI)
Total events: 184 (Mirtazapine), 160 (Others)
Heterogeneity: Chi2 = 0.21, df = 2 (P = 0.90); I2 =0.0%
Test for overall effect: Z = 1.58 (P = 0.12)
8 vs Sertraline
Behnke 2003
117/176
114/170
8.5 %
0.99 [ 0.82, 1.21 ]
Thase 2000
61/124
63/126
4.6 %
0.98 [ 0.71, 1.37 ]
300
296
13.1 %
0.99 [ 0.83, 1.17 ]
132/205
127/207
9.3 %
1.05 [ 0.86, 1.28 ]
205
207
9.3 %
1.05 [ 0.86, 1.28 ]
65/130
52/128
3.9 %
1.23 [ 0.86, 1.76 ]
48/78
39/79
2.9 %
1.25 [ 0.86, 1.81 ]
208
207
6.7 %
1.24 [ 0.96, 1.60 ]
Subtotal (99% CI)
Total events: 178 (Mirtazapine), 177 (Others)
Heterogeneity: Chi2 = 0.00, df = 1 (P = 0.96); I2 =0.0%
Test for overall effect: Z = 0.17 (P = 0.86)
9 vs Fluvoxamine
Schoemaker 2002
Subtotal (99% CI)
Total events: 132 (Mirtazapine), 127 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.64 (P = 0.52)
10 vs Venlafaxine
Benkert 2006
Guelfi 2000
Subtotal (99% CI)
Total events: 113 (Mirtazapine), 91 (Others)
0.1 0.2
0.5
Favours others
1
2
5
10
Favours Mirtazapine
(Continued . . . )
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
176
(. . .
Study or subgroup
Mirtazapine
Others
n/N
n/N
Risk Ratio
Weight
M-H,Fixed,99% CI
Continued)
Risk Ratio
M-H,Fixed,99% CI
Heterogeneity: Chi2 = 0.00, df = 1 (P = 0.95); I2 =0.0%
Test for overall effect: Z = 2.12 (P = 0.034)
11 vs Trazodone
Halikas 1995
van Moffaert 1995
Subtotal (99% CI)
25/50
20/50
1.5 %
1.25 [ 0.70, 2.22 ]
61/100
51/100
3.8 %
1.20 [ 0.86, 1.66 ]
150
150
5.2 %
1.21 [ 0.91, 1.61 ]
13/20
13/20
1.0 %
1.00 [ 0.55, 1.82 ]
20
20
1.0 %
1.00 [ 0.55, 1.82 ]
2439
2443
100.0 %
1.05 [ 0.99, 1.12 ]
Total events: 86 (Mirtazapine), 71 (Others)
Heterogeneity: Chi2 = 0.03, df = 1 (P = 0.86); I2 =0.0%
Test for overall effect: Z = 1.73 (P = 0.083)
12 vs Reboxetine
Schule 2006
Subtotal (99% CI)
Total events: 13 (Mirtazapine), 13 (Others)
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
Total (99% CI)
Total events: 1426 (Mirtazapine), 1358 (Others)
Heterogeneity: Chi2 = 27.22, df = 25 (P = 0.35); I2 =8%
Test for overall effect: Z = 2.03 (P = 0.043)
Test for subgroup differences: Chi2 = 16.63, df = 11 (P = 0.12), I2 =34%
0.1 0.2
0.5
Favours others
1
2
5
10
Favours Mirtazapine
CONTRIBUTIONS OF AUTHORS
All review authors contributed to the production of the protocol. NW, IMO and TAF identified studies for inclusion and checked the
methodological quality of studies. NW and IMO extracted data. NW performed the analyses. NW wrote the final review, which was
approved by the other authors.
DECLARATIONS OF INTEREST
NW has received research grants from the Japanese Ministry of Education, Science, Sports and Culture; and from the Japanese Ministry
of the Health, Labour and Welfare. He has also received speaking fees and research funds from Asahi Kasei, Dai-Nippon Sumitomo,
Eli Lilly, GlaxoSmithKline, Janssen, Otsuka, Pfizer and Schering-Plough.
TAF has received research funds and speaking fees from Astellas, Dai-Nippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Meiji,
Otsuka, Pfizer, Schering-Plough and Yoshitomi. He was on a research advisory board for Meiji and Mochida, and is currently on a
research advisory board for Sekisui Chemicals and the Takeda Science Foundation. The Japanese Ministry of Education, Science, and
Technology and the Japanese Ministry of Health Labor and Welfare have also funded his research.
IMO, AN, AC, CB, and RC have nothing to be declared.
Mirtazapine versus other antidepressive agents for depression (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
177
DIFFERENCES BETWEEN PROTOCOL AND REVIEW
The definition of the early response rates has been amended from that in the published protocol (“Early response rates: between 1 and
4 weeks, the time point closest to 2 weeks will be given preference”), because, after starting the review process, we recognised that all
trials reported outcomes at 2 weeks when trials gave information about early response rate.
The subgroup analyses have been amended from the published protocol in which there are five subgroup analyses (mirtazapine dosing,
comparator dosing, depression severity, treatment settings, elderly participants). The sensitivity analyses have been amended from
the published protocol in which there are six sensitivity analyses (excluding trials with unclear concealment of random allocation or
unclear double blinding, excluding trials whose dropout rate is greater than 20%, performing the worst case and best case scenario
ITT, excluding trials for which the response rates had to be calculated based on the imputation method or borrowed from other trials,
examination of ’wish bias’ by comparing mirtazapine as investigational drug versus mirtazapine as comparator, excluding studies funded
by the pharmaceutical company marketing mirtazapine).
These planned but not conducted analyses will be done in future updates of the review if adequate numbers of studies are available for
the analyses.
NOTES
This review is one of a number of separate reviews examining head-to-head comparisons as part of the multiple Meta-Analyses of New
Generation Antidepressants (MANGA) Study. These individual reviews were combined in a multiple-treatments meta-analysis and
published elsewhere (Cipriani 2009a).
INDEX TERMS
Medical Subject Headings (MeSH)
Antidepressive Agents [therapeutic use]; Antidepressive Agents, Tricyclic [∗ therapeutic use]; Cyclohexanols [therapeutic use]; Depression
[∗ drug therapy]; Mianserin [∗ analogs & derivatives; therapeutic use]; Randomized Controlled Trials as Topic; Venlafaxine Hydrochloride
MeSH check words
Adult; Humans
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Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Rachel Churchill