US Headache Consortium

Pharmacologic treatment for episodic migraine prevention in adults

According to guidelines released by the American Academy of Neurology and the American Headache Society,^[159]the following medications are established as effective and should be offered for migraine prevention (level A recommendation):

Antiepileptic drugs (AEDs): divalproex sodium, sodium valproate, topiramate
β-Blockers: metoprolol, propranolol, timolol
Triptans: frovatriptan for short-term MAMs prevention

The following medications are probably effective and should be considered for migraine prevention (level B recommendation):

Antidepressants: amitriptyline, venlafaxine
β-Blockers: atenolol, nadolol
Triptans: naratriptan, zolmitriptan for short-term MAMs prevention

The following medications are possibly effective and may be considered for migraine prevention (level C recommendation):

ACE inhibitors: lisinopril
Angiotensin receptor blockers: candesartan
α-Agonists: clonidine, guanfacine
AEDs: carbamazepine
β-Blockers: nebivolol, pindolol

NSAIDs and other complementary treatments for episodic migraine prevention in adults

The American Academy of Neurology and the American Headache Society also released guidelines regarding the use of NSAIDs and complementary treatments in preventing episodic migraine.^[160]

The following therapy is established as effective and should be offered for migraine prevention (level A recommendation):

Petasites (butterbur)

The following therapies are probably effective and should be considered for migraine prevention (level B recommendation):

NSAIDS: fenoprofen, ibuprofen, ketoprofen, naproxen, naproxen sodium
Herbal therapies, vitamins, and minerals: riboflavin, magnesium, MIG-99 (feverfew)
Histamines: histamine SC

The following therapies are possibly effective and may be considered for migraine prevention (level C recommendation):

NSAIDs: flurbiprofen, mefenamic acid
Herbal therapies, vitamins, and minerals: Co-Q10, estrogen
Antihistamines: cyproheptadine

Emergency department treatment

In 2016, the American Headache Society (AHS) released guidelines for the management of adults with acute migraine in the emergency department. They recommend intravenous metoclopramide, intravenous prochlorperazine, and subcutaneous sumatriptan to treat these patients (level B recommendation). Dexamethasone should be offered to these patients to prevent recurrence of headache (level B). Opioids (injectable morphine and hydromorphone) should be avoided.^{[161, 162]}

Preventive and acute treatment

An updated position statement from AHS in 2021 offers guidance on preventive and acute treatment of migraine.^{[163, 164]}Recommendations include:

Preventive migraine treatment

Consider preventive treatment for migraine patients in any of the following situations:

Migraine attacks are frequent (≥ 4 migraine headache days per month) and/or the attacks interfere with patients’ daily routines even with acute treatment
There is contradiction to, failure, or overuse of acute treatments
Acute treatments lead to adverse events

Oral treatments should be offered for migraine prevention. These include antiepileptic drugs, beta-blockers, and frovatriptan. Do not prescribe valproate sodium and topiramate to women who are not using birth control and who may become pregnant.

Start oral treatments at a low dose and titrate slowly.

Give oral treatments for at least 8 weeks to optimize therapeutic response.

Acute migraine treatment

Use evidence-based treatment at the first sign of a migraine attack.

Use NSAIDs (including aspirin), nonopioid analgesics, acetaminophen, or caffeinated analgesic combinations for mild‐to‐moderate attacks and migraine‐specific agents (triptans, dihydroergotamine) for moderate or severe attacks and mild‐to‐moderate attacks that respond poorly to NSAIDs or caffeinated combinations.

Use a nonoral option for select patients, including those with nausea or vomiting or those who have trouble swallowing.

Options for outpatient rescue include SC sumatriptan, DHE injection or intranasal spray, or corticosteroids. Inpatient options may include parenteral formulations of triptans, DHE, antiemetics, NSAIDs, anticonvulsants (eg, valproate sodium and topiramate, except in women of childbearing age who are not using reliable birth control), corticosteroids, and magnesium sulfate.

Medication

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Media Gallery

Migraine headache. Example of a visual migraine aura as described by a person who experiences migraines. This patient reported that these visual auras preceded her headache by 20-30 minutes.
Migraine headache. Example of a central scotoma as described by a person who experiences migraines. Note the visual loss in the center of vision.
Migraine headache. Example of a central scotoma as described by a person who experiences migraine headaches. Again note the visual loss in the center of vision.
Migraine headache. Example of visual changes during migraine. Multiple spotty scotomata are described by a person who experiences migraines.
Migraine headache. Frank visual field loss can also occur associated with migraine. This example shows loss of the entire right visual field as described by a person who experiences migraines.
International Headache Society criteria for migraine without aura.
Overview of migraine treatment. Five steps.
International Headache Society (IHS) classification of secondary headaches.

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Table 1. Abortive Medication Stratification by Headache Severity

Moderate	Severe	Extremely Severe
NSAIDs	Naratriptan	DHE (IV)
Isometheptene	Rizatriptan	Opioids
Ergotamine	Sumatriptan (SC,NS)	Dopamine antagonists
Naratriptan	Zolmitriptan	Lasmiditan
Rizatriptan	Almotriptan
Sumatriptan	Frovatriptan
Zolmitriptan	Eletriptan
Almotriptan	DHE (NS/IM)
Frovatriptan	Ergotamine
Eletriptan	Dopamine antagonists
Zavegepant intranasal	Zavegepant intranasal
Dopamine antagonists	Lasmiditan
DHE=Dihydroergotamine; NSAIDs=nonsteroidal anti-inflammatory drugs

Table 2. Preventive Drugs for Migraine

First line	High efficacy	Beta blockers Tricyclic antidepressants Divalproex Topiramate
First line	Low efficacy	Verapamil
Second line	High efficacy	Methysergide Flunarizine MAOIs CGRP inhibitors Botulinum toxin
Second line	Unproven efficacy	Cyproheptadine Gabapentin
MAOIs = monoamine oxidase inhibitors

Table 3. Preventive Medication for Comorbid Conditions

Comorbid Condition	Medication
Hypertension	Beta blockers
Angina	Beta blockers
Stress	Beta blockers
Depression	Tricyclic antidepressants, SSRIs
Overweight	Topiramate, protriptyline
Underweight	Tricyclic antidepressants (nortriptyline, protriptyline)
Epilepsy	Valproic acid, topiramate
Mania	Valproic acid
SSRIs = selective serotonin reuptake inhibitors

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Author

Jasvinder Chawla, MD, MBA Chief of Neurology, Hines Veterans Affairs Hospital; Professor of Neurology, Loyola University Medical Center

Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology, American Stroke Association

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Abbott Laboratories, advisory group.

Acknowledgements

Michelle Blanda, MD Chair, Department of Emergency Medicine, Summa Health System Akron City/St. Thomas Hospital; Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine

Michelle Blanda, MD, is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine