What is the best medication for migraine prophylaxis?

Best Medications for Migraine Prophylaxis

Beta blockers (propranolol, metoprolol, atenolol, or bisoprolol), topiramate, and candesartan are the first-line medications for migraine prophylaxis based on the most recent guidelines. 1, 2

Indications for Preventive Therapy

• Consider preventive treatment for patients who experience ≥2 migraine days per month with significant disability despite optimized acute treatment 1, 2
• Preventive therapy is indicated for patients using acute medications more than twice per week to avoid medication overuse headache 2, 3
• Patients with contraindications to or failure of acute treatments should be evaluated for preventive therapy 2
• Patients with uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, migrainous infarction) are candidates for preventive therapy 2

First-Line Medications

• Beta blockers without intrinsic sympathomimetic activity:

  • Propranolol (80-240 mg/day) - FDA approved for migraine prophylaxis with strong evidence for efficacy 1, 2, 4
  • Metoprolol, atenolol, or bisoprolol - also effective first-line options 1, 2

• Topiramate (100 mg/day):

  • Typically administered as 50 mg twice daily 2, 5
  • Shows significant efficacy within the first month of treatment 5
  • Particularly useful for patients concerned about weight gain 6

• Candesartan:

  • Effective first-line agent, particularly useful for patients with comorbid hypertension 1, 2

Second-Line Medications

• Amitriptyline (30-150 mg/day):

  • Particularly effective for patients with mixed migraine and tension-type headache 2, 3

• Flunarizine:

  • Effective second-line option where available 1

• Sodium valproate/divalproex sodium (500-1500 mg/day):

  • Effective second-line option but STRICTLY CONTRAINDICATED in women of childbearing potential due to teratogenic effects 1, 2, 3

Third-Line Medications

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab):
  • Consider when other preventive treatments have failed or are contraindicated 1
  • In Europe, regulatory restrictions limit use to patients in whom other preventive drugs have failed 1

Implementation of Preventive Therapy

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 2, 3
• Allow an adequate trial period of 2-3 months before determining efficacy 2, 3
• For CGRP monoclonal antibodies, efficacy should be assessed only after 3-6 months 1
• Monitor for medication overuse, which can interfere with preventive treatment 2, 3
• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 3

Medication-Specific Considerations

Propranolol

• Starting dose of 80 mg daily, with gradual titration to 160-240 mg daily for optimal migraine prophylaxis 4
• Available as extended-release capsules for once-daily dosing 4
• Shown to reduce migraine frequency in controlled trials 4

Topiramate

• Target dose of 100 mg/day (optimal balance of efficacy and tolerability) 6, 5
• Common side effects include paresthesia, fatigue, decreased appetite, and cognitive dysfunction 5, 7
• Extended-release formulations may have fewer cognitive side effects and better adherence 7
• Contraindicated in pregnancy (Category D) due to increased risk of cleft lip/palate 7

Non-Pharmacological Options

• Consider neuromodulatory devices, biobehavioral therapy, or acupuncture as adjuncts to medication or as stand-alone treatments when medications are contraindicated 1, 2
• Limited evidence exists for physical therapy, spinal manipulation, and dietary approaches 1

Common Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications 2, 3
• Inadequate duration of preventive trial (less than 2-3 months) 2, 3
• Starting with too high a dose, leading to poor tolerability and discontinuation 2, 3
• Not addressing comorbidities that may influence treatment selection (e.g., avoiding valproate in women of childbearing potential) 2, 3

Duration of Therapy

• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 1
• A useful measure to quantify success is calculating the percentage reduction in monthly migraine days 1