What medications are used for migraine prevention?

Migraine Prevention Medications

First-Line Preventive Agents

For most patients requiring migraine prophylaxis, start with propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (100 mg/day), or candesartan, as these have the strongest evidence for efficacy and are recommended as first-line agents by multiple guideline societies. 1, 2

Beta-Blockers

• Propranolol (80-240 mg/day) and timolol (20-30 mg/day) have the most consistent evidence for efficacy among all preventive medications, with good evidence from multiple controlled trials 3
• Alternative beta-blockers include atenolol, metoprolol, and nadolol, though evidence is more limited 3, 1
• Common adverse effects include fatigue, depression, nausea, dizziness, and insomnia, but these are generally well-tolerated and rarely cause discontinuation 3
• Beta-blockers should be avoided in patients with suspected glaucoma due to risk of precipitating angle-closure glaucoma 4

Topiramate

• Topiramate 100 mg/day (typically 50 mg twice daily) is the recommended target dose, balancing efficacy and tolerability 1, 2, 5
• Reduces migraine frequency by approximately 2 attacks per month, with effects beginning within the first month of treatment 5, 6
• The 50 mg/day dose shows suboptimal efficacy, while 200 mg/day causes significantly more tolerability issues without additional benefit 5, 7
• Most common adverse events are paresthesia (35-51%), fatigue, decreased appetite, nausea, and weight loss, occurring more frequently during titration 8, 7
• Titrate by 25 mg weekly to minimize side effects 8, 9
• Monitor for acute vision changes, eye pain, or halos in the first 2-4 weeks due to rare risk of angle-closure glaucoma 4

Angiotensin Receptor Blockers

• Candesartan is an excellent first-line choice, particularly for patients with comorbid hypertension, with strong evidence and no glaucoma contraindications 4, 1, 2
• Telmisartan is also recommended as first-line by recent guidelines 2
• Lisinopril has emerging evidence but requires more research 4, 2

Second-Line Preventive Agents

Antidepressants

• Amitriptyline (30-150 mg/day) has consistent evidence for efficacy and is the only antidepressant with strong support 3
• Particularly effective in patients with mixed migraine and tension-type headache or comorbid depression 3, 1
• Common adverse effects include drowsiness, weight gain, and anticholinergic symptoms 3
• Use cautiously in confirmed narrow-angle glaucoma without prior laser peripheral iridotomy 4

Anticonvulsants

• Divalproex sodium (500-1500 mg/day) and sodium valproate (800-1500 mg/day) have good evidence for efficacy 3, 1
• Absolutely contraindicated in women of childbearing potential due to teratogenic effects including neural tube defects 3, 4, 1, 2
• Adverse events include weight gain, hair loss, and tremor 3

NSAIDs

• Naproxen or naproxen sodium show modest effect in meta-analysis of controlled trials 3
• Most commonly reported adverse events are gastrointestinal symptoms (nausea, vomiting, gastritis) in 3-45% of patients 3

Third-Line: CGRP Monoclonal Antibodies

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when first- and second-line treatments have failed or are contraindicated 1, 2
• Efficacy should be assessed only after 3-6 months of treatment 1
• These agents have strong recommendations from recent guidelines for both episodic and chronic migraine 2

Additional Options

OnabotulinumtoxinA

• Recommended specifically for chronic migraine prevention only, not for episodic migraine 2

Other Agents

• Memantine and atogepant are suggested for episodic migraine prevention 2
• Oral magnesium has limited evidence but may be considered 2
• Gabapentin is not recommended for migraine prevention 2

Indications for Preventive Therapy

Consider preventive therapy when patients experience:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 3, 1
• Use of abortive medication more than twice per week (to avoid medication overuse headache) 3, 1
• Failure of or contraindications to acute treatments 3, 1
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 3, 1

Implementation Strategy

• Start with low doses and titrate slowly over 2-3 weeks to minimize adverse effects 1, 8
• Allow an adequate trial period of 2-3 months before determining efficacy 1
• Use headache diaries to track attack frequency, severity, duration, and treatment response 1
• Consider tapering or discontinuing after 6-12 months of successful therapy to determine if continued treatment is necessary 1

Critical Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent acute medication use (>2 days per week), which can interfere with preventive treatment 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 1
• Prescribing valproate to women of childbearing potential without verifying pregnancy status and contraception 4, 1, 2
• Using beta-blockers in patients with suspected angle-closure glaucoma without ophthalmology evaluation 4