Migraine Headache: Symptoms, Causes, Medication & Treatment
Migraine: This lecture reviews migraine headaches including symptoms, causes, triggers, types, diagnosis, treatment, medications, and more!
Guest Author
Guest Author: Sarah Mason, PA-C, Neurology
The lecture below was written by guest author Sarah Mason who is a PA-C in neurology.
Medical illustrations were created and provided by EZmed.
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Migraine Headache
Most people are familiar with migraines and have been affected by them in some way.
Whether they suffer from migraines themselves or know someone else who does, migraines are an exceedingly common condition affecting a large portion of the population.
Migraines carry a significant amount of morbidity, so it is important to understand how to properly diagnose patients with this condition, as well as provide appropriate treatment.
Primary care providers will generally manage initial treatment for migraines, but patients with refractory or intractable migraines are often referred to a neurologist or headache specialist.
The lecture below will review the following about migraines:
Definition
Signs & Symptoms
Phases
Epidemiology
Causes
Triggers
Types
Diagnosis
Treatment
Prevention
Don’t miss the clinical pearls at the end!
Leave a comment at the end if this lecture helped!
Migraines: Definition, meaning, signs, symptoms, phases, epidemiology, causes, pathophysiology, triggers, types, diagnosis, treatment, and more!
What Are Migraines?
Let’s start with a quick definition and overview of migraines.
Defintion
Migraine (also called migraine headache) is a headache characterized by moderate to severe pain that is often debilitating in nature.
Migraine vs Headache
Migraines are typically distinguished from headaches by the severity.
Headaches tend to be more mild and dull in nature, whereas migraines are more severe and often debilitating.
Other usual characteristics of migraines include unilateral presentation, throbbing pain, and longer duration.
Let’s review migraine symptoms in more detail next!
Migraine vs Headache: Definition, symptoms, and features/characteristics of migraines vs headaches
Migraine Symptoms & Phases
There are 4 phases of a migraine:
Prodrome
Aura
Headache
Postdrome
1. Prodrome
Timeframe = Hours to days prior to migraine
Fatigue
Irritability
Mood changes
Appetite changes
Nausea
Difficulty sleeping
Difficulty focusing
Photophobia/phonophobia
2. Aura
Timeframe = Gradually evolve over 5 minutes; Can last up to 60 minutes in most cases
Aura = Sensory disturbance or symptom that usually occurs shortly before a migraine
Visual disturbances - Also known as scintillating scotomas
Flashing lights, blind spots, “zig-zag” patterns
Loss of vision
Numbness or tingling
Weakness
Dizziness
Speech and hearing changes
Brainstem aura (previously known as basilar migraine)
Aura with symptoms that originate from the brainstem including dysarthria, vertigo, tinnitus, diplopia, decreased level of consciousness, or ataxia
**Some patients can have migraine aura without the headache, known as acephalgic migraine.
3. Headache
Timeframe = 4-72 hours
Typically unilateral (one-sided) but can be bilateral
Moderate to severe intensity
Throbbing quality, made worse with movement
Light and/or sound sensitivity
Nausea and/or vomiting
Patients will often say they have to lay in a cool, dark room for relief
4. Postdrome
Timeframe = 24-48 hours following headache
Mood changes
Difficulty concentrating
Fatigue
Migraine Symptoms: Chart showing the 4 phases of a migraine including the prodrome, aura, headache, and postdrome stages
Epidemiology of Migraines
About 12% of the population suffers from migraines
More common in women (17%) versus men (6%)
An estimated 39 million Americans have migraines, according to estimates from the American Migraine Foundation
Migraine is ranked as the second leading cause of disability worldwide, second only to low back pain
Migraine has a strong genetic basis
If one parent has a history of migraine, the child has a 40% risk of also developing migraines
If both parents have a history of migraine, this increases to 75%
Causes of Migraines
The causes of migraine are complex and multifactorial, and still not fully understood.
There are several theories about the pathogenesis of migraine:
Vascular theory
Vasoconstriction in the brain causes aura, and vasodilation causes migraine.
This is an older theory which is no longer thought to be valid.
Cortical spreading depression
Cortical spreading depression is thought to be responsible for migraine aura.
This is a complex process involving a wave of depolarization in the brain that leads to changes in blood flow, metabolism, and neuronal function, as well as activation of the trigeminovascular system.
Neurogenic inflammation from release of neurotransmitters and neuromodulators
Calcitonin gene-related peptide (CGRP) - CGRP is a neurotransmitter that is released in migraine attacks and bonds to the CGRP receptors.
This causes vasodilation and inflammation, as well as the pain experienced in migraine.
Some of the new migraine medications work by targeting CGRP.
Substance P and neurokinin A are other inflammatory mediators thought to be released in migraine.
Migraine Causes: Pathophysiology of migraines including vascular theory (vasodilation and vasoconstriction), cortical spreading depression, and neurogenic inflammation
**CGRP = calcitonin gene-related peptide
Migraine Triggers
Patients with migraine will often endorse certain triggers for their headaches, including:
Stress
Weather Changes
Menstrual Cycle
Food
Alcohol
Sleep Disturbance
Sound or Lights
Smoking
Migraine Triggers: List of potential triggers causing migraine headaches including weather changes, certain foods, alcohol, smoking, sleep disturbances, etc.
Diagnosis & Types of Migraines
Migraines are generally a clinical diagnosis.
When diagnosing migraine, be sure to distinguish:
Migraine with aura vs migraine without aura
Chronic (15+ days a month) vs episodic (<15 days a month)
With status migrainosus (migraine lasting >72 hours)
Intractable (refractory to normal treatment)
Migraine without Aura
Diagnostic Criteria according to the International Classification of Headache Disorders (ICHD-3):
Migraine without aura:
At least 5 attacks fulfilling criteria below
Headache attacks lasting 4 to 72 hours (untreated or unsuccessfully treated)
Headache has at least two of the following:
Unilateral location
Pulsating quality
Moderate or severe pain intensity
Aggravation by or causing avoidance of routine physical activity (walking or climbing stairs)
During a headache, at least one of the following:
Nausea and/or vomiting
Photophobia and phonophobia
Migraine Types: Diagnosis criteria for migraine without aura including symptoms, duration, and frequency
Migraine with Aura
Diagnostic Criteria according to the International Classification of Headache Disorders (ICHD-3):
Migraine with aura:
At least 2 attacks fulfilling criteria below
One or more of the following fully reversible aura symptoms:
Visual
Sensory
Speech and/or language
Motor
Brainstem
Retinal
At least three of the following six characteristics:
At least one aura symptom spreads gradually over five or more minutes
Two or more aura symptoms occur in succession
Each aura symptom lasts 5 to 60 minutes
At least one aura symptom is unilateral
At least one aura symptom is positive
The aura is accompanied, or followed within 60 minutes, by the headache
Migraine Types: Diagnosis criteria for migraines with aura including symptoms and characteristics
Migraine Variants
Also be aware of migraine variants - A migraine that manifests itself in a form other than a headache:
Retinal Migraine
Visual symptoms affecting one eye (temporary blindness, blind spot, visual disturbance), which are not always accompanied by headache.
In retinal migraine, the visual disturbance is coming from the retina rather than from the brain as in a migraine with aura.
Migraine with Brainstem Aura
Aura with symptoms that originate from the brainstem including dysarthria, vertigo, tinnitus, diplopia, decreased level of consciousness, or ataxia.
Hemiplegic Migraine
Patient experiences temporary unilateral weakness with migraine.
Can be familial or sporadic.
For any of these conditions, would NOT want to use triptan medications as rescue due to the vasoconstriction caused by triptans (more on treatments below).
Migraine Variants: Other types of migraines include variants such as retinal migraine, migraine with brainstem aura, and hemiplegic migraine
**LOC = level of consciousness
Migraine “Red Flags”
Be aware of migraine “red flags” that may indicate a more serious pathology.
SNOOP4 is a helpful mnemonic for remembering these red flags, which will require further workup to evaluate.
SNOOP4
S = Systemic Signs and Disorders
Is the patient immunocompromised?
Symptoms such as fever, chills, night sweats?
Differential includes meningitis/encephalitis, arteritis, Lyme, AIDS, malignancy, etc.
N = Neurologic Symptoms
Altered mental status, loss of consciousness, focal neurologic deficit?
These could indicate pathologies such as stroke, intracranial hemorrhage, malignancy, infection, etc.
O = Onset new or changed, or patient over 50 years old
Is the patient experiencing a change in their typical headache pattern?
Is this a new headache in a patient 50 years or older?
Differential includes temporal arteritis or malignancy
O = Onset of “thunderclap” headache
Did the headache come on abruptly, or go from no pain to severe pain in a matter of seconds-minutes?
Thunderclap headache is concerning for subarachnoid hemorrhage, aneurysm, or AVM (arteriovenous malformations)
P(4) = Papilledema, pulsatile tinnitus, positional, precipitated by exercise/valsalva, pregnancy
Would want to evaluate the patient for pseudotumor cerebri, intracranial hypotension, aneurysm, mass or tumor, infection, venous sinus thrombosis, carotid artery dissection
Migraine Red Flags Mnemonic: Headache signs and symptoms that are red flags can be remembered with the mnemonic SNOOP4
**AIDS = acquired immunodeficiency syndrome; ICH = intracerebral/intracranial hemorrhage; AVM = arteriovenous malformation; IIH = idiopathic intracranial hypertension
Diagnostic Workup
As noted above, migraine is generally a clinical diagnosis.
However, in the presence of any of the red flag symptoms/SNOOP4 findings noted, further testing is recommended.
Brain MRI
Usually the best imaging unless the patient has a contraindication to MRI, since it shows more detail than a head CT and does not involve radiation.
Contrast or no contrast:
Contrast allows for a more detailed view of brain structures, which can be helpful for evaluating inflammation, blood flow, tumors, etc.
Consider ordering contrast if you have suspicion for conditions such as multiple sclerosis, pituitary mass, seizure disorder, malignancy, etc.
Be cautious of renal impairment or contrast allergies
MRA (magnetic resonance angiography)
Consider MRA if there is concern for aneurysm, pulsatile tinnitus, dissection, etc.
MRV (magnetic resonance venography)
Consider MRV to rule out venous sinus thrombosis
Venous sinus thrombosis can commonly mimic pseudotumor cerebri
MRV is often ordered when evaluating for pseudotumor, in addition to a brain MRI and lumbar puncture (LP)
Head CT
Consider in:
Emergent situations
Trauma, initial stroke workup, etc.
When MRI is not available
Contraindications to MRI
Eye Exam
Consider an eye exam to rule out migraine mimics such as idiopathic intracranial hypertension (IIH) and evaluate visual disturbances
Blood Work/Labs
ESR, CRP to evaluate for temporal arteritis, which can mimic migraine
Other labs such as CBC, CMP, TSH, can be helpful for ruling out systemic conditions that may be causing or provoking the migraines
Lumbar Puncture
Lumbar puncture if there is concern for multiple sclerosis, idiopathic intracranial hypertension, infection, etc.
Migraine "Red Flag” Workup: Diagnostic tests for headaches with red flags include imaging (brain MRI, MRA, MRV, head CT), eye exam, labs/blood work, lumbar puncture, etc.
Migraine Medications & Treatment
There are 2 main options to treat migraines:
Non-Pharmacological (without medication)
Pharmacological (with medication)
Non-Pharmacological
Non-Pharmacological = These are management options that do not involve medication
Non-Medication Treatment Options:
Starting a headache diary to identify patterns and triggers
Increasing hydration
Regular sleep
Regular exercise
Cognitive behavioral therapy
Biofeedback
Wearable devices
Examples include Cefaly and Nerivio
These devices can be for migraine rescue or prevention, and usually work through repetitive nerve stimulation and desensitization.
Avoid medication overuse headache
It is common for patients with chronic migraine to take over the counter analgesics or rescue medications frequently; however, if these are being used 3+ times a week, the patient may be suffering from medication overuse headache.
Limiting use of these medications to < 2-3 times a week will improve this.
Supplements that have shown some efficacy for reducing migraines:
Magnesium 400-600mg nightly
Riboflavin 400mg daily
Melatonin 3mg nightly
CoQ10 100mg TID
Butterbur is not recommended anymore due to potential liver toxicity
Migraine Treatment: Non-pharmacological management options for migraine headaches
Pharmacological - Acute/Rescue Medications
Acute/Rescue Medications = These are medications that can be taken at headache onset.
NSAIDs
Examples: Ibuprofen, Naproxen, Diclofenac, Ketorolac (often given as IM injection)
Mechanism of Action (MOA): Inhibition of COX enzyme and prostaglandin synthesis
Side effects: Upset stomach, nausea, vomiting, constipation, diarrhea, dizziness, drowsiness, stomach ulcer, reflux. Can lead to medication overuse headache if taken too frequently.
Contraindications: History of GI bleed or ulcers, cardiovascular disease, renal impairment
Triptans
Examples: Sumatriptan, Rizatriptan, Eletriptan, Naratriptan
MOA: Serotonin-receptor agonists which produce vasoconstriction
Side effects: Chest tightness, fatigue, flushing, myalgias. Can lead to medication overuse headache if taken too frequently.
Contraindications: Cardiovascular or cerebrovascular disease, PVD (peripheral vascular disease), uncontrolled hypertension, hemiplegic/basilar migraine, patients with liver impairment
*Can be taken with NSAIDs
Fioricet
Acetaminophen/Butalbital/Caffeine
MOA: Barbiturate (butalbital), analgesic (acetaminophen) and adenosine antagonist (caffeine)
Side effects: Can be habit forming (it is controlled in some states). Can also cause medication overuse headache if used frequently. Drowsiness, dizziness, nausea, sedation.
Contraindications: Cannot take with other CNS depressants or if patient has used an MAO inhibitor in the past 14 days. Caution in history of liver impairment, history of substance abuse.
Ergotamine/Caffeine
MOA: Works on multiple receptors including 5-HT-1B/1D, dopamine, and alpha-adrenoreceptors (agonist). Does cause vasoconstriction
Side effects: Nausea, vomiting, insomnia, cramping. Can lead to medication overuse headache if taken too frequently.
Contraindications: Patients with PVD, CAD (coronary artery disease), CVA (cerebrovascular accident), uncontrolled hypertension, impaired renal or hepatic function, pregnancy, or taking medications that are CYP3A4 inhibitors.
Lasmiditan
MOA: Selectively bind to the 5-HT1F receptor (serotonin receptor agonist)
Side effects: Drowsiness is a major side effect with this medication - patients are unable to drive or operate heavy machinery for 8 hours after taking this medication. Can also cause dizziness and nausea.
Contraindications: Use with caution when taken with other CNS depressants. Use with caution with serotonergic agents as it does have risk of serotonin syndrome.
CGRP Medications
Ubrogepant (Ubrelvy), Rimegepant (Nurtec)
These are great medications for patients who have contraindications to triptan medications. They also do not contribute to medication overuse headaches.
MOA: Antagonize CGRP receptor to block activity of CGRP, a neurotransmitter involved in migraine pathogenesis (see “causes” above).
Side effects: Nausea, drowsiness, stomach pain
Contraindications: Contraindicated with concomitant use of strong CYP3A4 inhibitors
Prednisone or Medrol Dose Taper
This is useful for breaking a bad headache cycle that has not been responsive to normal rescue medications.
Avoid use in patients with uncontrolled hyperglycemia
Antiemetics
Examples: Ondansetron, Metoclopramide, Promethazine, Prochlorperazine
MOA: Most work through dopamine receptor antagonism
Side effects: Risk of QT interval prolongation and torsades de pointes, dystonia, tardive dyskinesia
Muscle Relaxants
Examples: Tizanidine, Baclofen
Can be used as migraine rescue treatment, sometimes used as preventative.
Side effect: Drowsiness - avoid use with other CNS depressants
Migraine Medications: List of treatment options and medication names for the management of migraine headaches
Pharmacological - Preventative Medications
Preventative Medications = These are medications that help prevent migraines.
Usually consider starting a patient on preventatives if:
They are having > 4-8 headache days a month
Headaches are interfering with their ability to function normally
You suspect medication overuse headache
**There are several categories of medication that can be used for preventing migraines, and it is important to consider the potential side effects when choosing a medication.
For example, using a beta blocker for migraines in a patient with high blood pressure may be beneficial.
Antidepressants
Nortriptyline
MOA: Tricyclic antidepressant
Side effects: Anticholinergic side effects, generally dose related. Fatigue, dry mouth, constipation, weight gain, hypertension, blurred vision, palpitations.
Contraindications: Recent use of MAOI drug, acute MI (myocardial infarction), seizure disorder (small risk of lowering seizure threshold). Caution in patients > 65, patient with significant cardiac history, patients with history of glaucoma or BPH (benign prostatic hyperplasia).
Venlafaxine
MOA: SNRI (serotonin and norepinephrine reuptake inhibitor)
Side effects: Hypertension, dry mouth, insomnia, nausea
Contraindications: Recent use of MAOI drug. Caution in patients with uncontrolled blood pressure.
Blood Pressure Medications (Antihypertensives)
Propranolol
MOA: Beta blocker
Side effects: Fatigue, hypotension, bradycardia, impotence
Contraindications: History of asthma or COPD, bradycardia
Verapamil
MOA: Calcium channel blocker
Side effects: Constipation, bradycardia, dizziness, nausea, flushing, drowsiness, hypotension.
Contraindications: History of asthma or COPD, cardiac conduction disorders, ACS, bradycardia.
Antiepileptics
Topiramate
MOA: Stimulates GABA-A receptor activity
Side effects: Brain fog, numbness and tingling, fatigue, decreased appetite.
Monitor CMP periodically!
Contraindications: History of kidney stones, liver disease. Pregnancy category D. Avoid use in women of child-bearing age if possible; if using, counsel patient to use 2 forms of birth control.
Depakote (divalproex sodium, valproate sodium, valproic acid)
MOA: Thought to increase GABA levels in the brain
Side effects: Dizziness, hair loss, nausea, tremor, weight gain, pancreatitis, thrombocytopenia, liver failure.
Monitor CBC, CMP, and depakote levels!
Contraindications: Liver disease. Pregnancy category D. Avoid use in women of child-bearing age if possible; if using, counsel patient to use 2 forms of birth control.
CGRP Medications
Emgality (galcanezumab), Ajovy (fremanezumab), Aimovig
MOA: Monoclonal antibody against calcitonin gene-related peptide receptor. These medications are administered by self injection by the patient every 28 days.
Side effects: Most common side effect is injection site reaction or pain at injection site.
Contraindications: Hypersensitivity reaction
Nurtec (rimegepant)
Nurtec is an oral dissolving tablet that can be used as a preventative medication (every other day) or taken as a rescue medication at headache onset.
MOA: Antagonist of the CGRP receptors
Side effects: Nausea, drowsiness
Contraindications: History of hypersensitivity to Nurtec
Botox
Botox is injected into 31 spots on the head and neck every 3 months and can be an effective treatment for patients with chronic migraine who have not had relief with other migraine treatments.
Most common side effects with this would be head and neck pain after injection. It is also possible to develop eyelid or neck weakness, although this resolves in about 3 months.
Migraine Medications: Treatment options and medication/drug names for preventative migraine headache therapy
Clinical Pearls
Insurance Barriers
Most of the CGRP medications and Botox are not covered by insurance until patients have tried and failed at least 2-3 other oral medications.
Sometimes you can make a case for not trying a class of oral medications due to patient contraindications (such as a history of bradycardia for propranolol).
“How many days a month are you headache free?”
This is a good question for chronic migraine patients because they often have a difficult time estimating how many days a month they have headaches.
Migraine patients also often underestimate the true number of migraine days (not counting migraine prodrome/postdrome).
Start low and go slow!
For many of the migraine medications, starting at a very low dose and increasing slowly over the course of several weeks is helpful for minimizing side effects and maximizing adherence.
Many of the preventative headache medications do not work immediately.
Set expectations with patients that an adequate trial of medication is about 2-3 months to see full efficacy.
If migraines are well controlled on a medication regimen for 6-12 months or longer, can consider gradually weaning off medication.
Migraines in pregnancy
Try to avoid prescription medication use if possible, but discuss risk/benefit with patient.
Generally, fioricet and tylenol are considered safe as rescue treatment options.
Patients can also try the supplements listed above.
Wearable devices such as Cefaly and Nerivio are also safe in pregnancy.
However, always discuss with the patient’s OB/GYN prior to starting any of these.
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References:Pescador Ruschel M., De Jesus O.; Migraine Headache; National Library of Medicine; Updated Feb 2023; Accessed Feb 2023; https://www.ncbi.nlm.nih.gov/books/NBK560787/Hien H. PharmD, Gonzalez A. MD; Migraine Headache Prophylaxis; American Family Physician; 2019; 99(1): 17-24; Accessed Feb 2023; https://www.aafp.org/pubs/afp/issues/2019/0101/p17.htmlLew C., Punnapuzha S.; Migraine Medications; National Library of Medicine; May 2022; Accessed Feb 2023; https://www.ncbi.nlm.nih.gov/books/NBK553159/Ngo M., Tadi P.; Ergotamine/Caffeine; National Library of Medicine; July 2022; Accessed Feb 2023; https://www.ncbi.nlm.nih.gov/books/NBK555953/SNOOP: Red Flags for Migraine; Time of Care Online Medicine Notebook; Accessed Feb 2023; https://www.timeofcare.com/snoop-red-flags-for-headache/The Timeline of a Migraine Attack; Managing Migraine, Migraine Essentials; American Migraine Foundation; Jan 2018; Accessed Feb 2023; https://americanmigrainefoundation.org/resource-library/timeline-migraine-attack/