What are the options for migraine prophylaxis?

Migraine Prophylaxis Options

For migraine prophylaxis, start with propranolol (80-240 mg/day), timolol (20-30 mg/day), or topiramate (100 mg/day) as first-line agents, with the choice depending on comorbidities—use beta-blockers for patients with hypertension or anxiety, topiramate for those with obesity or epilepsy, and reserve amitriptyline (30-150 mg/day) for patients with comorbid tension-type headache or insomnia. 1

Indications for Starting Preventive Therapy

You should initiate prophylaxis when patients meet any of these criteria:

• Two or more migraine attacks per month causing disability lasting ≥3 days 2, 1
• Using acute/abortive medications more than twice weekly (risk of medication overuse headache) 2, 1
• Contraindication to or failure of acute treatments 2, 1
• Uncommon migraine variants: hemiplegic migraine, prolonged aura, or migrainous infarction 2, 1

First-Line Preventive Agents

Beta-Blockers (Strongest Evidence)

Propranolol is FDA-approved and has the most robust evidence, with moderate certainty that it reduces monthly migraine days by 1.27 days and increases the proportion achieving ≥50% reduction in attacks (relative risk 1.65). 3, 4

• Dosing: Start 80 mg once daily (extended-release), titrate to 120-160 mg daily; maximum 240 mg/day 4, 1
• Timolol 20-30 mg/day is equally effective with strong evidence 2, 1
• Alternative beta-blockers (atenolol, metoprolol, nadolol) have limited but supportive evidence 2, 1
• Avoid beta-blockers with intrinsic sympathomimetic activity (acebutolol, pindolol)—they are ineffective 2

Clinical pearl: Propranolol is superior for pure migraine, while amitriptyline works better for mixed migraine-tension headache. 2, 5

Topiramate

Topiramate 100 mg/day (typically 50 mg twice daily) is recommended as first-line with emerging strong evidence. 1

• Particularly useful for patients with comorbid obesity (causes weight loss) or epilepsy
• Requires slow titration to minimize cognitive side effects

Candesartan

Candesartan is a first-line agent, especially valuable for patients with comorbid hypertension. 1

• Offers dual benefit of blood pressure control and migraine prevention

Second-Line Preventive Agents

Amitriptyline

Amitriptyline 30-150 mg/day has consistent evidence and is the only tricyclic with proven efficacy. 2, 5

• Start low: 10-25 mg at bedtime, titrate gradually 5
• Superior to propranolol when patients have mixed migraine and tension-type headache 2, 5
• Side effects: drowsiness, weight gain, dry mouth, constipation 2, 5
• Nortriptyline lacks evidence despite being in the same class 5

Anticonvulsants (Valproate/Divalproex)

• Divalproex sodium 500-1500 mg/day or sodium valproate 800-1500 mg/day 2, 1
• Strictly contraindicated in women of childbearing potential due to severe teratogenic effects 1, 5

Flunarizine

Flunarizine 10 mg/day is effective where available (not in the US). 1, 5

Third-Line: CGRP Monoclonal Antibodies

Reserve for patients who have failed or cannot tolerate first- and second-line options: 1

• Erenumab, fremanezumab, galcanezumab, eptinezumab
• Require 3-6 months to assess efficacy (longer than traditional agents) 1
• Expensive but well-tolerated with favorable side effect profile

Implementation Strategy

Titration and Trial Duration

• Start low, titrate slowly over weeks to months to optimize tolerability 1, 5
• Adequate trial requires 2-3 months at therapeutic dose before declaring failure 2, 1, 5
• Clinical benefits may not appear for 2-3 months even at target dose 5

Monitoring

Use headache diaries to track: 2

• Attack frequency, severity, duration
• Disability and functional impact
• Acute medication use
• Adverse effects

Duration and Discontinuation

• After 6-12 months of successful control, consider tapering to determine if prophylaxis can be discontinued 1
• Taper gradually over several weeks, especially with beta-blockers (avoid rebound) 4
• Success metric: Calculate percentage reduction in monthly migraine days 1

Critical Pitfalls to Avoid

Medication Overuse Headache

Using acute medications >2 days per week causes rebound headaches that interfere with preventive treatment efficacy. 2, 1, 5

• Ergotamine, opioids, triptans, and butalbital/caffeine combinations are the worst offenders 2
• Address overuse before or concurrent with starting prophylaxis

Inadequate Trial Duration

Stopping preventive therapy before 2-3 months is the most common reason for perceived treatment failure. 1, 5

Starting Dose Too High

Aggressive initial dosing leads to poor tolerability and discontinuation. 1

• Always start at the low end and titrate based on response and side effects

Ignoring Comorbidities

• Never use valproate in women of childbearing potential 1, 5
• Leverage comorbidities: beta-blockers for hypertension/anxiety, topiramate for obesity, amitriptyline for insomnia/tension headache 1, 5

Non-Pharmacological Adjuncts

Consider as additions to medication or when medications are contraindicated: 1

• Neuromodulatory devices (limited evidence)
• Biobehavioral therapy (biofeedback, cognitive behavioral therapy)
• Acupuncture (not superior to sham but may help some patients)
• Aerobic exercise and progressive strength training 5