What are the options for migraine prophylaxis?

Migraine Prophylaxis Options

Start with beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate 100 mg/day, or candesartan as first-line agents, with the choice depending on comorbidities and patient-specific factors such as hypertension, weight concerns, or epilepsy. 1, 2, 3

Indications for Starting Prophylaxis

Consider preventive therapy when patients experience:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 2
• Use of abortive medications more than twice weekly (risk of medication-overuse headache) 2, 3
• Contraindications to or failure of acute treatments 2
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 2

First-Line Prophylactic Medications

Beta-Blockers

• Propranolol (80-240 mg/day) and timolol (20-30 mg/day) have the strongest evidence and FDA approval 2, 3
• Alternative beta-blockers with moderate evidence: atenolol, metoprolol, nadolol, bisoprolol 1, 3
• Avoid beta-blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) as they are ineffective 3
• Common side effects: dizziness, fatigue, bradycardia 1

Topiramate

• Target dose: 100 mg/day (typically 50 mg twice daily) 2, 4
• Reduces migraine frequency by approximately 2 attacks per month 4, 5
• Particularly useful for patients concerned about weight gain, currently overweight, or with coexisting epilepsy 3, 4
• Start at 25 mg/day with weekly 25-50 mg increments to minimize side effects 4, 6
• Most common adverse events: paresthesia (dose-related), fatigue, decreased appetite, cognitive dysfunction, weight loss 4, 5
• Contraindicated in women of childbearing potential due to teratogenic effects 3
• Effective even in chronic migraine (≥15 headache days/month) and with medication overuse 7

Candesartan

• First-line agent, particularly useful for patients with comorbid hypertension 1, 2, 3
• Well-tolerated alternative when beta-blockers are contraindicated 1

Second-Line Prophylactic Medications

Amitriptyline

• Dose: 30-150 mg/day 2, 3
• Only antidepressant with consistent evidence for migraine prophylaxis 3
• Particularly effective in patients with mixed migraine and tension-type headache 2, 3
• Common side effects: sedation, dry mouth, weight gain 1

Valproate/Divalproex Sodium

• Dose: valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day 2, 3
• Good evidence for efficacy 1, 2
• Strictly contraindicated in women of childbearing potential due to teratogenic effects 1, 2, 3

Flunarizine

• Dose: 10 mg/day 1
• Proven efficacy where available (not available in the United States) 1, 3
• Side effects: sedation, weight gain, abdominal pain, depression, extrapyramidal symptoms (particularly in elderly) 1

Third-Line Medications: CGRP Monoclonal Antibodies

Consider when first- and second-line treatments have failed or are contraindicated 1, 2, 3:

• Erenumab, fremanezumab, galcanezumab (strong recommendations) 2
• Eptinezumab (intravenous, weaker evidence) 2
• Assess efficacy only after 3-6 months of treatment 1, 3

Chronic Migraine-Specific Option

OnabotulinumtoxinA (Botox)

• FDA-approved specifically for chronic migraine prophylaxis (≥15 headache days/month), NOT for episodic migraine 1, 2, 8
• Delivered using the Phase III Research Evaluating Migraine Prophylaxis Therapy protocol 1
• Assess efficacy only after 6-9 months 1
• Requires administration by neurologist or headache specialist 1
• Serious risks include spread of toxin effects causing botulism-like symptoms (muscle weakness, swallowing/breathing problems) 8

Implementation Strategy

Dosing Principles

• Start with low dose and titrate slowly until clinical benefits achieved or side effects limit further increases 1, 2, 3
• Allow adequate trial period of 2-3 months for oral agents before determining efficacy 1, 3
• For CGRP antibodies: 3-6 months; for onabotulinumtoxinA: 6-9 months 1, 3

Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, and treatment response 1, 2
• Calculate percentage reduction in monthly migraine days to quantify success 1, 3

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if discontinuation is possible 1, 3
• This minimizes unnecessary drug exposure 1

Medication Overuse Management

• Limit acute medications to no more than twice weekly to prevent medication-overuse headache 2, 3
• Address medication overuse before or concurrent with preventive therapy initiation 1, 2

Non-Pharmacological Options

Consider as adjuncts to medication or stand-alone when medications contraindicated 1, 2:

• Neuromodulatory devices (some evidence) 1, 2
• Biobehavioral therapy (some evidence) 1, 2
• Acupuncture (not superior to sham in controlled trials) 1, 2
• Limited to no evidence for physical therapy, spinal manipulation, dietary approaches 1

Critical Pitfalls to Avoid

• Failing to recognize medication-overuse headache from frequent acute medication use, which interferes with preventive efficacy 2, 3
• Inadequate trial duration (<2-3 months for oral agents); premature discontinuation prevents accurate efficacy assessment 2, 3
• Starting with excessively high doses, leading to poor tolerability and treatment discontinuation 2, 3
• Using valproate/divalproex or topiramate in women of childbearing potential due to teratogenic effects 1, 2, 3
• Prescribing onabotulinumtoxinA for episodic migraine (ineffective and not indicated) 2
• Using beta-blockers with intrinsic sympathomimetic activity 3