What are the best preventive medications for an adult patient with a history of frequent or severe migraines?

Best Preventive Medications for Migraines

For adults with frequent or severe migraines requiring preventive therapy, propranolol (80-240 mg/day) or timolol (20-30 mg/day) are the strongest first-line options, with topiramate (50-100 mg/day) and candesartan as equally effective alternatives based on the most recent guidelines. 1

When to Initiate Preventive Therapy

Preventive therapy should be started when patients meet any of these criteria:

• Two or more migraine attacks per month with disability lasting 3 or more days 1
• Using acute medications more than twice per week, which creates risk for medication-overuse headache 1
• Contraindications to or failure of acute treatments 1
• Uncommon migraine conditions such as hemiplegic migraine, migraine with prolonged aura, or migrainous infarction 1

First-Line Preventive Medications

Beta-Blockers (Strongest Evidence)

• Propranolol 80-240 mg/day has the strongest evidence with FDA approval and consistent efficacy data 1
• Timolol 20-30 mg/day is equally effective with strong evidence 1
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol, though with slightly less robust evidence 1
• Avoid beta-blockers in patients with asthma, bradycardia, or those who practice competitive sports 2

Topiramate

• Topiramate 50-100 mg/day (typically 50 mg twice daily) is FDA-approved with strong efficacy evidence 1
• Particularly beneficial for patients with comorbid obesity due to associated weight loss 1
• Common adverse effects include cognitive slowing, paresthesias, and kidney stones 3

Candesartan

• Candesartan is a first-line agent especially useful for patients with comorbid hypertension 1
• Provides dual benefit of blood pressure control and migraine prevention 1

Second-Line Preventive Medications

Amitriptyline

• Amitriptyline 30-150 mg/day is the most effective antidepressant for migraine prevention 1
• Optimal choice for patients with mixed migraine and tension-type headache, or comorbid depression/anxiety/insomnia 1, 4
• Start low (10-25 mg at bedtime) and titrate slowly to minimize anticholinergic side effects 1

Valproate/Divalproex

• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day are highly effective 1
• Strictly contraindicated in women of childbearing potential due to teratogenic effects 1, 3
• Adverse effects include weight gain, hair loss, tremor, and hepatotoxicity 1

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, or galcanezumab should be considered when 2-3 oral preventive medications have failed or are contraindicated 1
• Administered monthly via subcutaneous injection 1
• Require 3-6 months for adequate efficacy assessment, significantly longer than oral agents 1
• Significantly more expensive ($5,000-$6,000 annually) than oral preventives 1
• Eptinezumab (IV) and atogepant (oral) have weaker evidence 1

OnabotulinumToxinA (Botox)

• Recommended ONLY for chronic migraine (≥15 headache days per month), NOT for episodic migraine 1
• Specifically recommended AGAINST for episodic migraine prevention 1
• Requires 6-9 months for adequate efficacy assessment 1
• Serious risks include spread of toxin effects causing botulism-like symptoms, swallowing/breathing problems, and potential death 5

Implementation Strategy

Titration and Trial Period

• Start with low doses and titrate slowly until clinical benefits are achieved or side effects limit further increases 1
• Allow 2-3 months for adequate trial of oral preventive medications before determining efficacy 1
• Use headache diaries to track attack frequency, severity, duration, and treatment response 1

Duration of Therapy

• Continue successful preventive therapy for 6-12 months before attempting to taper 1
• After stability period, consider tapering or discontinuing to determine if ongoing treatment is necessary 1
• Calculate percentage reduction in monthly migraine days to quantify success 1

Critical Pitfalls to Avoid

• Never allow acute medication use to exceed 2 days per week, as this creates medication-overuse headache that undermines preventive therapy 1, 6
• Do not abandon a preventive medication before completing adequate trial period: 2-3 months for oral agents, 3-6 months for CGRP antibodies, 6-9 months for onabotulinumtoxinA 1
• Screen for medication-overuse headache before starting preventive therapy (≥10 days/month for triptans, ≥15 days/month for NSAIDs) 1
• Do not start with excessively high doses, which leads to poor tolerability and discontinuation 1
• Verify no contraindications: avoid valproate in women of childbearing potential, beta-blockers in asthmatics, topiramate in patients with kidney stones 1, 3

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, and relaxation training should be offered alongside medication as effective adjuncts 1
• Neuromodulatory devices can be considered when medications are contraindicated 1
• Identify and modify triggers: sleep hygiene, regular meals, hydration, stress management 1
• Complementary treatments with probable efficacy include riboflavin, magnesium, feverfew, and petasites 3