What are the medication options for migraine prophylaxis?

Migraine Prophylaxis Medication Options

First-line medications for migraine prophylaxis include beta blockers (propranolol, timolol), topiramate, candesartan, and amitriptyline, with selection based on patient characteristics and comorbidities. 1

When to Consider Prophylactic Treatment

Preventive treatment should be initiated when:

• Patient experiences ≥2 migraine days per month with significant disability despite optimized acute treatment 1
• Attacks produce disability lasting 3 or more days per month 1
• Acute medications are used more than twice per week 1
• Contraindications to or failure of acute treatments 1
• Presence of uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, migrainous infarction) 1

First-Line Medication Options

Beta Blockers

• Propranolol: 80-240 mg/day 1, 2

  • FDA-approved for migraine prophylaxis
  • Usual effective dose range: 160-240 mg once daily 2
  • Contraindicated in asthma, bradycardia, heart block
  • Common side effects: fatigue, dizziness, insomnia, depression

• Timolol: 20-30 mg/day 1

  • Similar efficacy to propranolol
  • Similar contraindication profile to propranolol

• Other beta blockers: Atenolol, bisoprolol, metoprolol 1

  • Must be beta blockers without intrinsic sympathomimetic activity

Anticonvulsants

• Topiramate: 50-200 mg/day 1, 3

  • Optimal dose: 100 mg/day (best balance of efficacy and tolerability) 3
  • Reduces migraine frequency by approximately 2 attacks/month 3
  • Common side effects: paresthesia, cognitive dysfunction, weight loss
  • Particularly effective in chronic migraine, even with medication overuse 4
  • May be more effective than propranolol at lower doses (50 mg/day) 5

• Divalproex sodium: 500-1500 mg/day 1

  • Good evidence for efficacy
  • Particularly effective for prolonged or atypical migraine aura
  • Side effects: hair loss, tremor, weight gain
  • Strictly contraindicated in women of childbearing potential due to teratogenicity 1

Other First-Line Options

• Candesartan: 16-32 mg/day 1

  • Angiotensin II receptor blocker
  • Well-tolerated alternative to beta blockers
  • Useful in patients with hypertension comorbidity

• Amitriptyline: 30-150 mg/day 1

  • Tricyclic antidepressant
  • May be superior to propranolol for mixed migraine and tension-type headache 1
  • Side effects: weight gain, drowsiness, anticholinergic symptoms

Second-Line Medication Options

• Flunarizine: Calcium channel blocker 1

  • Not available in the United States
  • Common side effects: weight gain, depression

• Sodium valproate: 800-1500 mg/day 1

  • Similar efficacy and side effect profile to divalproex sodium
  • Contraindicated in women of childbearing potential

Third-Line Medication Options

• CGRP monoclonal antibodies: 1
  • Erenumab, fremanezumab, galcanezumab, eptinezumab
  • Reserved for patients who have failed other preventive medications
  • Administered as monthly or quarterly injections
  • Generally well-tolerated but expensive

Adjunctive Treatments

• Topiramate as adjunctive therapy: Can be added to existing prophylactic treatment 6

  • Effective when added to propranolol or flunarizine
  • Titrate slowly: start at 25 mg/day, increase by 25-50 mg weekly to maximum of 100 mg/day

• Non-pharmacological options: 1

  • Neuromodulatory devices
  • Biobehavioral therapy
  • Acupuncture
  • Consider as adjuncts or when medications are contraindicated

Treatment Implementation

1. Start with low dose and increase slowly until benefits are achieved without adverse effects
2. Adequate trial period: Clinical benefits may take 2-3 months to appear
3. Assess efficacy: After 2-3 months for oral medications; 3-6 months for CGRP antibodies
4. Consider tapering after 6-12 months of stability
5. Monitor for medication overuse headache, especially if acute medications are used frequently

Common Pitfalls to Avoid

• Inadequate dosing: Ensure target therapeutic doses are reached
• Insufficient trial duration: Allow 2-3 months before determining efficacy
• Overlooking contraindications: Particularly valproate in women of childbearing potential
• Ignoring comorbidities: Select medications that may benefit coexisting conditions
• Medication overuse: Monitor and address overuse of acute medications

Special Considerations

• Failure of one preventive treatment does not predict failure with other drug classes
• Adherence issues can be improved with simplified dosing schedules
• Avoid butalbital-containing medications and opioids due to risk of dependence and medication overuse headache
• Approximately 90% of migraine patients can be effectively managed in primary care with proper medication selection and dosing