What are the most commonly used medications for migraine prevention?

Most Popular Medications for Migraine Prevention

The most commonly used first-line medications for migraine prevention are propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (100 mg/day), amitriptyline (30-150 mg/day), and divalproex sodium/sodium valproate (500-1500 mg/day). 1

First-Line Preventive Agents

The medications with the strongest evidence and most widespread use include:

Beta-Blockers

• Propranolol (80-240 mg/day) has consistent evidence for efficacy and is FDA-approved for migraine prevention 2, 1
• Timolol (20-30 mg/day) also has strong evidence supporting its use 2, 1
• These agents are particularly effective in patients with migraine alone (propranolol may be superior to amitriptyline in this population) 2
• Common side effects include fatigue, depression, nausea, dizziness, and insomnia, though these are generally well-tolerated 2
• Beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) are ineffective and should be avoided 2

Anticonvulsants

• Topiramate (100 mg/day) is a first-line agent with strong evidence from multiple large randomized controlled trials involving nearly 3000 patients 1, 3, 4
• The 100 mg/day dose provides optimal efficacy without the increased side effects seen at 200 mg/day 3, 4
• Topiramate reduces migraine frequency by approximately 2 attacks per month and decreases acute medication use 4
• Divalproex sodium (500-1500 mg/day) and sodium valproate (800-1500 mg/day) have good evidence for efficacy 2, 1
• These agents are especially useful in patients with prolonged or atypical migraine aura 2
• Critical caveat: Valproate products are strictly contraindicated in women of childbearing potential due to teratogenic effects including neural tube defects 2, 1

Tricyclic Antidepressants

• Amitriptyline (30-150 mg/day) is the only antidepressant with consistent evidence for migraine prevention 2, 1
• It may be superior to propranolol in patients with mixed migraine and tension-type headache 2
• Common side effects include drowsiness, weight gain, and anticholinergic symptoms 2

Angiotensin Receptor Blockers

• Candesartan is recommended as a first-line agent, particularly useful for patients with comorbid hypertension 1

Second-Line and Alternative Agents

NSAIDs

• Naproxen or naproxen sodium showed modest effect in meta-analysis of placebo-controlled trials 2
• Side effect rates were not significantly higher than placebo, though gastrointestinal symptoms (nausea, vomiting, gastritis, blood in stool) occurred in 3-45% of participants 2

Other Beta-Blockers

• Atenolol, metoprolol, and nadolol have limited evidence of moderate effect 2

Calcium Channel Blockers

• Flunarizine (10 mg/day) has proven efficacy where available, though not in the United States 2, 1
• Verapamil, nifedipine, and nimodipine have poor quality evidence suggesting only modest effect 2

CGRP Monoclonal Antibodies (Third-Line)

• Erenumab, fremanezumab, galcanezumab, and eptinezumab should be considered when first- and second-line treatments have failed or are contraindicated 1
• Galcanezumab 120 mg monthly (with 240 mg loading dose) demonstrated significant reductions in monthly migraine headache days in both episodic and chronic migraine 5
• These agents require 3-6 months to assess efficacy 1

Implementation Strategy

Dosing Approach

• Start with low doses and titrate slowly until clinical benefits are achieved or side effects limit further increases 2, 1
• For topiramate specifically, use 25 mg increments weekly to allow habituation and minimize cognitive side effects 3, 6, 7
• Allow adequate trial period of 2-3 months before determining efficacy for traditional preventives 2, 1

Common Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications (more than twice weekly), which interferes with preventive treatment 2, 1
• Starting with too high a dose, leading to poor tolerability and premature discontinuation 1
• Inadequate trial duration (less than 2-3 months) before declaring treatment failure 2, 1
• Prescribing valproate to women of childbearing potential without addressing teratogenic risks 1

Duration and Discontinuation

• After 6-12 months of successful therapy (defined as significant reduction in monthly migraine days), consider tapering or discontinuing treatment to determine if it can be stopped 2, 1
• Methysergide requires mandatory 3-4 week drug holidays after each 6-month course due to risk of retroperitoneal and retropleural fibrosis 2