What are the first-line treatments for migraine prophylaxis?

First-Line Migraine Prophylaxis

Beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate (100 mg/day), and candesartan are the first-line treatments for migraine prophylaxis, with propranolol and timolol having the strongest evidence for efficacy. 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 per month 1
• Using abortive medications more than twice per week, which puts patients at risk for medication overuse headache 1
• Contraindications to or failure of acute treatments 1
• Uncommon migraine conditions such as hemiplegic migraine, prolonged aura, or migrainous infarction 1

First-Line Medication Options

Beta-Blockers (Strongest Evidence)

• Propranolol 80-240 mg/day is FDA-approved with strong evidence for efficacy and should be the initial choice for most patients 1, 2
• Timolol 20-30 mg/day also has strong evidence supporting its use 1
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol if propranolol is not tolerated 1

Topiramate

• Target dose is 100 mg/day (typically 50 mg twice daily), with no additional benefit observed at 200 mg/day 1, 3
• Start at 25 mg daily and titrate by 25 mg weekly to minimize side effects 1, 4
• Particularly useful for patients concerned about weight gain or who are currently overweight, as it causes weight loss 3
• Efficacy can be seen as early as the first month of treatment 4
• Most common side effects are paresthesia, fatigue, decreased appetite, nausea, and taste perversion 3

Candesartan

• Especially useful for patients with comorbid hypertension 1
• Serves as an effective first-line agent with good evidence 1

Second-Line Options

When first-line agents fail or are contraindicated:

• 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 effective where available 1

Implementation Strategy

Dosing Approach

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 1
• Allow an adequate trial period of 2-3 months before determining efficacy for oral agents 1
• For topiramate specifically, use 25 mg weekly increments to a target of 100 mg/day 1, 4

Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 1
• Screen for medication overuse, which can interfere with preventive treatment 1
• Calculate percentage reduction in monthly migraine days to quantify success 1

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 1

Third-Line Options

When first- and second-line treatments fail:

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered 1
• These require 3-6 months for efficacy assessment 1

Non-Pharmacological Adjuncts

• Neuromodulatory devices, biobehavioral therapy, or acupuncture can be used as adjuncts or stand-alone treatments when medications are contraindicated 1

Critical Pitfalls to Avoid

• Do not fail to recognize medication overuse headache from frequent use of acute medications (more than twice weekly) 1
• Do not conduct inadequate trial duration (less than 2-3 months) before declaring treatment failure 1
• Do not start with too high a dose, which leads to poor tolerability and discontinuation 1
• Do not prescribe valproate to women of childbearing potential due to severe teratogenic effects 1