First-Line Migraine Prevention
Start with propranolol 80-240 mg/day or topiramate 100 mg/day as first-line preventive therapy for recurrent migraines. 1
When to Initiate Preventive Therapy
Preventive therapy is indicated when patients experience any of the following 1:
- ≥2 migraine attacks per month causing disability lasting ≥3 days
- Using acute medications more than twice weekly (risk of medication-overuse headache)
- Contraindications to or failure of acute treatments
- Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction)
First-Line Medication Options
Beta-Blockers (Preferred for Hypertension)
- Propranolol 80-240 mg/day has the strongest evidence and FDA approval for migraine prevention 1, 2
- Timolol 20-30 mg/day is equally effective with strong supporting evidence 1
- Alternative beta-blockers include atenolol, bisoprolol, or metoprolol if propranolol is not tolerated 1
- Particularly useful in patients with comorbid hypertension 1
Topiramate (Preferred for Obesity)
- Target dose: 100 mg/day (typically 50 mg twice daily) 1, 3
- Demonstrated efficacy in multiple large randomized controlled trials, reducing migraine days by 3.5 days per month compared to placebo 3
- Preferred for patients with obesity due to associated weight loss 1
- Start at 25 mg daily and titrate by 25 mg weekly to minimize side effects 4
- Efficacy can be observed as early as the first month, though full assessment requires 2-3 months 4
Candesartan (Alternative First-Line)
- Effective first-line agent, especially with comorbid hypertension 1, 5
- Provides dual benefit of blood pressure control and migraine prevention 1
Implementation Strategy
Dosing Approach
- Start low and titrate slowly to minimize side effects and improve tolerability 1
- For propranolol: begin at 80 mg/day and increase as needed to 240 mg/day 1
- For topiramate: start at 25 mg/day, increase by 25 mg weekly to target of 100 mg/day 4
Duration of Trial
- Continue treatment for 2-3 months before assessing efficacy 1, 4
- Use headache diaries to track attack frequency, severity, duration, and medication use 1
- After 6-12 months of successful therapy, consider tapering to determine if discontinuation is possible 1
Second-Line Options (If First-Line Fails)
- Amitriptyline 30-150 mg/day - particularly effective for patients with comorbid depression, anxiety, or mixed migraine/tension-type headache 1
- Flunarizine 5-10 mg/day - effective where available, comparable efficacy to propranolol 1
- Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day - effective but strictly contraindicated in women of childbearing potential due to teratogenic effects 1
Third-Line: CGRP Monoclonal Antibodies
Consider when 2-3 oral preventive medications have failed 1:
- Erenumab, fremanezumab, or galcanezumab administered monthly via subcutaneous injection 1
- Require 3-6 months for efficacy assessment (longer than oral agents) 1
- Significantly more expensive ($5,000-$6,000 annually) 1
Critical Pitfalls to Avoid
- Do not fail to recognize medication-overuse headache from frequent acute medication use (≥10 days/month for triptans, ≥15 days/month for NSAIDs) before starting preventive therapy 1
- Do not start with too high a dose - this leads to poor tolerability and discontinuation 1
- Do not conduct inadequate trial duration (less than 2-3 months) before declaring treatment failure 1
- Do not prescribe valproate to women of childbearing potential - it is teratogenic 1
- Do not allow continued frequent use of acute medications while on preventive therapy - this interferes with preventive efficacy 1
Non-Pharmacological Adjuncts
Consider alongside medication 1:
- Neuromodulatory devices (when medications contraindicated)
- Biobehavioral therapy (cognitive behavioral therapy, biofeedback, relaxation training)
- Acupuncture (though not superior to sham in controlled trials)
- Trigger modification (sleep hygiene, regular meals, hydration, stress management)