What are the recommended treatments for migraine prophylaxis?

Migraine Prophylaxis: Recommended Treatments

First-Line Prophylactic Medications

Beta-blockers, topiramate, and candesartan are the first-line medications for migraine prophylaxis, with propranolol (80-240 mg/day) and timolol (20-30 mg/day) having the strongest evidence for efficacy. 1

• Propranolol is FDA-approved for migraine prophylaxis with robust clinical trial data demonstrating effectiveness in reducing migraine frequency 1, 2
• Timolol (20-30 mg/day) represents another beta-blocker option with strong evidence 1
• Alternative beta-blockers including atenolol, bisoprolol, or metoprolol can be used when propranolol or timolol are not tolerated 1
• Topiramate (100 mg/day, typically 50 mg twice daily) is recommended as first-line therapy, with clinical trials showing 46% of patients achieving at least 50% reduction in migraine frequency 1, 3, 4
• Candesartan is particularly useful for patients with comorbid hypertension 1

Second-Line Prophylactic Medications

When first-line agents fail or are contraindicated, move to second-line options:

• Amitriptyline (30-150 mg/day) is particularly effective in patients with mixed migraine and tension-type headache 1
• Sodium valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) are effective but strictly contraindicated in women of childbearing potential due to teratogenic effects 1
• Flunarizine is an effective second-line option where available 1

Third-Line Medications: CGRP Monoclonal Antibodies

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when other preventive treatments have failed or are contraindicated. 1

• These agents require 3-6 months of treatment before efficacy can be properly assessed, longer than the 2-3 months needed for oral agents 1

Indications for Preventive Therapy

Initiate prophylaxis when patients meet any of these criteria:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 1, 5
• Using abortive medication more than twice per week to avoid medication overuse headache 1, 5
• Contraindications to or failure of acute treatments 1, 5
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 1

Implementation Strategy

Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases, allowing an adequate trial period of 2-3 months before determining efficacy. 1, 5

• For topiramate, titrate by 25 mg weekly to target dose of 100 mg/day 3, 4
• No additional efficacy is observed with topiramate 200 mg/day compared to 100 mg/day, but tolerability issues increase significantly 3, 4
• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 1, 5

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 1
• A useful measure to quantify success is calculating the percentage reduction in monthly migraine days 1

Critical Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications (more than twice weekly), which can interfere with preventive treatment 1, 5
• Inadequate duration of preventive trial (less than 2-3 months for oral agents) before declaring treatment failure 1
• Starting with too high a dose, leading to poor tolerability and discontinuation 1
• Prescribing valproate to women of childbearing potential without addressing contraception, given severe teratogenic effects 1

Non-Pharmacological Options

Consider as adjuncts to medication or as stand-alone treatments when medications are contraindicated:

• Neuromodulatory devices 1
• Biobehavioral therapy (biofeedback, relaxation training) 1
• Acupuncture, though not superior to sham acupuncture in controlled trials 1

Special Considerations for Topiramate

While topiramate is effective and FDA-approved for migraine prophylaxis, important considerations include:

• Most common adverse events are paresthesia (dose-related and most common cause of discontinuation), fatigue, decreased appetite, nausea, diarrhea, weight decrease, and taste perversion 3, 4, 6
• Topiramate should especially be considered for patients concerned about weight gain, currently overweight, or with coexisting epilepsy 3
• Cognitive dysfunction can occur and should be monitored 4
• One trial failed to demonstrate topiramate was as effective as propranolol, supporting propranolol's position as the most thoroughly evaluated first-line agent 7