What calcium channel blockers (CCBs) are best for treating headaches, specifically migraines?

Flunarizine is the Most Effective Calcium Channel Blocker for Headache Prevention

Among calcium channel blockers, flunarizine at 10 mg/day has the strongest evidence for efficacy in migraine prevention, though it is not available in the United States. For patients in countries where flunarizine is available, it should be the first-choice calcium channel blocker for migraine prophylaxis 1.

Evidence-Based Selection of Calcium Channel Blockers

First-Line CCB (Where Available):

• Flunarizine (10 mg/day): Has proven efficacy in multiple controlled trials for migraine prevention 1
  • Demonstrated consistent positive results in 5 studies 1
  • Response rates comparable to beta-blockers like propranolol 2
  • Important side effects to monitor: sedation, weight gain, depression, and extrapyramidal symptoms (especially in elderly patients) 1

Alternative CCBs (When Flunarizine Unavailable):

• Verapamil: Has modest evidence for efficacy in migraine prevention

  • Evidence is of poor quality but suggests some benefit 1
  • Three controlled studies showed improvement in 10/12,8/14, and 20/23 patients respectively 3
  • Higher doses (320 mg/day) may be more effective than lower doses (240 mg/day) 3
  • Common side effects: dizziness, constipation, edema, and flushing 1

• Nimodipine: Mixed evidence

  • Two trials showed significant benefits while three showed no difference from placebo 1
  • Overall evidence quality is poor 1

Comparative Efficacy with Other Preventive Medications

When selecting a preventive medication for migraine, it's important to note that calcium channel blockers are not typically first-line agents. The evidence-based hierarchy for migraine prevention is:

1. First-line preventive agents 1:

   • Propranolol (80-240 mg/day)
   • Timolol (20-30 mg/day)
   • Amitriptyline (30-150 mg/day)
   • Divalproex sodium (500-1,500 mg/day)
   • Sodium valproate (800-1,500 mg/day)

2. Second-line agents (including calcium channel blockers)

Special Considerations for Calcium Channel Blockers

For Cluster Headache:

• Verapamil is the preferred calcium channel blocker for cluster headache prevention 4, 5
  • Dosing is higher than for cardiovascular indications (360-720 mg/day)
  • Requires three times daily dosing for optimal effect
  • May need to tailor timing of doses to attack patterns (e.g., higher evening dose for nocturnal attacks) 4
  • ECG monitoring recommended at higher doses due to risk of heart block

Important Caveats:

• Diltiazem has no evidence supporting its use in migraine prevention 1
• Beta-blockers with intrinsic sympathomimetic activity (e.g., acebutolol, pindolol) are ineffective for migraine prevention and should be avoided 1
• Calcium channel blockers may take 4-8 weeks to show full preventive effect
• For patients with both migraine and hypertension, consider a beta-blocker like propranolol as first-line to address both conditions

Practical Algorithm for CCB Selection:

1. Determine if patient is in a country where flunarizine is available

   • If YES: Start flunarizine 10 mg daily (preferably at bedtime to minimize daytime sedation)
   • If NO: Consider verapamil starting at 80 mg three times daily, titrating up to 240-320 mg/day as needed

2. Monitor for effectiveness over 8-12 weeks

   • If inadequate response to verapamil, may increase to 480 mg/day with appropriate cardiac monitoring

3. If CCBs fail or are contraindicated, switch to a first-line agent like propranolol or amitriptyline

4. For patients with comorbid conditions:

   • Depression: prefer amitriptyline over CCBs
   • Hypertension: prefer beta-blockers over CCBs
   • Epilepsy: prefer valproate over CCBs

Remember that calcium channel blockers generally have more modest efficacy for migraine prevention compared to first-line agents like beta-blockers, antidepressants, and anticonvulsants.