What is the best medication for daily migraine prophylaxis?

Best Medication for Daily Migraine Prophylaxis

For most patients requiring daily migraine prophylaxis, propranolol (80-240 mg/day) or topiramate (100 mg/day) should be your first-line choice, with the decision between them based on comorbidities and side effect profiles. 1

First-Line Prophylactic Medications

The strongest evidence supports three medication classes as first-line options:

Beta-Blockers (Strongest Overall Evidence)

• Propranolol (80-240 mg/day) has the most robust evidence for efficacy and is FDA-approved for migraine prophylaxis. 1
• Timolol (20-30 mg/day) is also FDA-approved with strong evidence, though less commonly used. 1
• Alternative beta-blockers including atenolol, bisoprolol, or metoprolol can be considered if propranolol is not tolerated. 1
• Critical contraindication: Avoid beta-blockers in patients with suspected angle-closure glaucoma, as they can precipitate acute angle closure. 2

Topiramate (Best Evidence in Chronic Migraine)

• Topiramate 100 mg/day is the optimal dose balancing efficacy and tolerability. 1, 3, 4, 5
• Topiramate is the ONLY medication proven effective in randomized controlled trials specifically for chronic migraine (≥15 headache days/month). 6
• Large multicenter trials demonstrate reduction of approximately 2 migraines per month, with 49% of patients achieving ≥50% reduction in migraine frequency at 100 mg/day. 5
• Efficacy appears within the first month of treatment at therapeutic doses. 5
• Start at 25-50 mg/day and titrate by 25 mg weekly to minimize side effects. 7, 4
• Approximately 25% of patients respond to lower doses (50 mg/day), though 50% will ultimately require 100 mg/day for optimal response. 7

Candesartan (Excellent Safety Profile)

• Candesartan is particularly useful for patients with comorbid hypertension and has the cleanest safety profile in glaucoma patients. 1, 2
• This ARB represents a first-line option with strong evidence for efficacy. 1

Second-Line Prophylactic Medications

When first-line agents fail or are contraindicated:

Amitriptyline

• Dosing: 30-150 mg/day, particularly effective in patients with mixed migraine and tension-type headache or comorbid depression. 1, 2
• Use cautiously in confirmed narrow-angle glaucoma without prior laser peripheral iridotomy. 2

Valproate/Divalproex Sodium

• Dosing: 500-1500 mg/day, but ABSOLUTELY CONTRAINDICATED in women of childbearing potential due to teratogenic effects. 1, 2
• This is a critical pitfall to avoid—always verify pregnancy status before prescribing. 2

Special Consideration: Chronic Migraine (≥15 Headache Days/Month)

OnabotulinumtoxinA (Botox)

• OnabotulinumtoxinA is the ONLY FDA-approved therapy specifically for chronic migraine prophylaxis. 6
• The Phase III PREEMPT trials demonstrated reductions in headache days, migraine episodes, cumulative headache hours, and improved quality of life. 6
• This should be administered by a neurologist or headache specialist using the PREEMPT protocol. 6
• For chronic migraine specifically, consider topiramate as initial oral therapy while arranging specialist referral for onabotulinumtoxinA. 6

Implementation Algorithm

Step 1: Determine Migraine Frequency

• Episodic migraine (≥2 attacks/month with ≥3 days disability): Start with propranolol, topiramate, or candesartan. 1
• Chronic migraine (≥15 headache days/month): Topiramate is the only oral agent with proven efficacy; consider onabotulinumtoxinA referral. 6

Step 2: Screen for Contraindications and Comorbidities

• Hypertension present: Candesartan or propranolol preferred. 1, 2
• Glaucoma suspected: Candesartan or topiramate; avoid beta-blockers. 2
• Depression/anxiety: Amitriptyline preferred. 1, 2
• Overweight/obesity: Topiramate preferred (causes weight loss). 3, 4
• Women of childbearing age: Avoid valproate entirely. 1, 2

Step 3: Titration and Trial Period

• Allow 2-3 months at therapeutic dose before declaring treatment failure. 1
• Start low and titrate slowly to minimize side effects and improve adherence. 1
• Use headache diaries to objectively track frequency, severity, and disability. 6, 1

Step 4: Assess for Medication Overuse

• Limit acute medication use to no more than 2 days per week to prevent medication-overuse headache. 6, 1
• Medication overuse can interfere with preventive treatment efficacy. 1

Common Pitfalls to Avoid

• Inadequate trial duration: Preventive medications require 2-3 months at therapeutic dose before efficacy can be determined. 1
• Starting at too high a dose: This leads to poor tolerability and discontinuation, particularly with topiramate. 1, 7
• Prescribing valproate to women of childbearing potential: This is absolutely contraindicated due to severe teratogenic effects. 1, 2
• Failing to recognize medication-overuse headache: Frequent acute medication use (>2 days/week) perpetuates chronic migraine. 6, 1
• Using beta-blockers in angle-closure glaucoma: This can precipitate acute angle closure. 2

Side Effect Profiles to Counsel Patients

Topiramate

• Most common: paresthesias (dose-related), weight loss, cognitive dysfunction ("word-finding difficulty"), fatigue, nausea. 3, 4, 5
• Rare but serious: acute angle-closure glaucoma (monitor for vision changes, eye pain, halos in first 2-4 weeks). 2

Propranolol

• Most common: fatigue, bradycardia, hypotension, exercise intolerance, depression. 1
• Contraindications: asthma, heart block, severe bradycardia. 1

Amitriptyline

• Most common: dry mouth, constipation, weight gain, sedation, urinary retention. 1, 2
• Anticholinergic effects can theoretically worsen angle-closure risk. 2

When to Consider Third-Line Options

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be reserved for patients who have failed or cannot tolerate multiple first- and second-line agents. 1
• These require 3-6 months for efficacy assessment and are typically managed by specialists. 1