Migraine Prevention Medication
For patients with frequent and severe migraines, especially those with comorbid depression or anxiety, amitriptyline (30-150 mg/day) is the optimal first-line choice as it effectively treats both migraine and mood disorders simultaneously. 1
First-Line Medication Selection Algorithm
Choose based on comorbidities:
Depression or anxiety present: Amitriptyline 30-150 mg/day is superior because it addresses both migraine and mood disorders in a single agent 1
Hypertension present: Propranolol (80-240 mg/day) or candesartan provide dual benefit for both conditions 1, 2
Obesity present: Topiramate 100 mg/day (typically 50 mg twice daily) offers weight loss as an additional benefit 1
No significant comorbidities: Propranolol (80-240 mg/day) or timolol (20-30 mg/day) have the strongest evidence and FDA approval 1, 2
Implementation Strategy
Start low and titrate slowly to minimize side effects and improve tolerability 1:
- Begin amitriptyline at 10-25 mg at bedtime, increase by 10-25 mg weekly to target dose of 30-150 mg/day 1
- Begin propranolol at 80 mg daily, titrate to 80-240 mg daily (most patients achieve control at 160 mg) 2
- Begin topiramate at 25 mg daily, increase by 25 mg weekly to target of 100 mg/day 1
Allow adequate trial period of 2-3 months before declaring treatment failure, as clinical benefits may not appear immediately 1, 2
Second-Line Options When First-Line Fails
If first-line agents fail or are not tolerated:
Sodium valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) are effective second-line agents 1
Strictly contraindicated in women of childbearing potential due to severe teratogenic effects 1
Flunarizine (5-10 mg once daily at night) is effective where available, comparable to propranolol and topiramate 1
Avoid in elderly patients due to increased risk of extrapyramidal symptoms and depression 1
Screen for depression and Parkinson's disease before initiating, as flunarizine may exacerbate these conditions 1
Third-Line: CGRP Monoclonal Antibodies
Reserve for patients who have failed 2-3 oral preventive medications 1:
- Erenumab, fremanezumab, or galcanezumab administered monthly via subcutaneous injection 1
- Require 3-6 months for adequate efficacy assessment, longer than oral agents 1
- Significantly more expensive ($5,000-$6,000 annually) compared to oral agents 1
Critical Indications for Preventive Therapy
Initiate preventive treatment when:
- ≥2 migraine attacks per month with disability lasting ≥3 days per month 1
- Using acute medications more than twice per week (risk of medication overuse headache) 1
- Contraindications to or failure of acute treatments 1
- Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 1
Common Pitfalls to Avoid
Medication overuse headache: Rule out before starting preventive therapy, defined as using acute medications ≥10 days/month for triptans or ≥15 days/month for NSAIDs 1. This can interfere with preventive treatment effectiveness.
Inadequate trial duration: Failing to allow 2-3 months at therapeutic dose before declaring failure 1. Patients and providers often abandon effective treatments prematurely.
Starting dose too high: Leading to poor tolerability and discontinuation 1. Always start low and titrate gradually.
Ignoring contraindications: Particularly valproate in women of childbearing potential (teratogenic) 1, propranolol in patients with bradycardia or heart block 2, and flunarizine in patients with depression or Parkinsonism 1.
Duration and Discontinuation
After 6-12 months of successful therapy, consider tapering preventive treatment to determine if it can be discontinued 1. A useful measure is calculating the percentage reduction in monthly migraine days to quantify success 1.
Non-Pharmacological Adjuncts
Offer alongside medication for enhanced efficacy 1: