What are the first-line and second-line treatment options for migraine prophylaxis?

Migraine Prophylaxis: First-Line and Second-Line Treatment Options

First-line treatments for migraine prophylaxis include propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (100 mg/day), amitriptyline (30-150 mg/day), divalproex sodium (500-1500 mg/day), sodium valproate (800-1500 mg/day), and flunarizine. 1

When to Consider Prophylactic Treatment

Prophylactic treatment should be initiated when:

• Migraine episodes occur ≥2 times per month
• Attacks are prolonged and disabling
• Poor response to acute treatments
• Quality of life is reduced between attacks 1

The target goal for preventive treatment is a 50% reduction in attack frequency.

First-Line Treatment Options

Beta Blockers

• Propranolol (80-240 mg/day): FDA-approved for migraine prevention with strong evidence. Has demonstrated efficacy in reducing migraine frequency in controlled studies 1, 2
• Timolol (20-30 mg/day): FDA-approved with strong evidence for efficacy 1

Anticonvulsants

• Topiramate (100 mg/day): FDA-approved with strong evidence. The 100 mg/day dose provides optimal balance of efficacy and tolerability 1, 3

  • Particularly beneficial for patients concerned about weight gain or who are overweight 3
  • Shows efficacy as early as the first month of treatment 4
  • Common side effects include paresthesia, fatigue, decreased appetite, and cognitive dysfunction 3

• Divalproex sodium (500-1500 mg/day) and Sodium valproate (800-1500 mg/day): Effective options but contraindicated in pregnancy due to teratogenic effects 1

Other First-Line Options

• Amitriptyline (30-150 mg/day): Effective tricyclic antidepressant option 1
• Flunarizine: Calcium channel blocker with solid evidence, particularly useful for hemiplegic migraine 1

Second-Line Treatment Options

If inadequate response to first-line agents after 6-8 weeks, consider:

Angiotensin Pathway Modulators

• Candesartan (8-32 mg daily): Provides additional benefit for patients with comorbid hypertension 1
• Telmisartan: Alternative ARB option 1

Antidepressants

• Venlafaxine (75-150 mg daily): SNRI with evidence for migraine prevention, may help with comorbid insomnia 1

Non-Pharmacological Approaches

These can be used alone for mild cases or as adjuncts to medication:

• Supplements:

  • Magnesium (400-600 mg daily)
  • Riboflavin (400 mg daily)
  • Coenzyme Q10 1

• Behavioral interventions:

  • Cognitive behavioral therapy
  • Relaxation training
  • Thermal biofeedback
  • Mindfulness-based treatment 1

• Lifestyle modifications:

  • Regular sleep schedule
  • Adequate hydration
  • Identification and avoidance of personal triggers using a headache diary
  • Regular aerobic exercise
  • Stress management techniques 1

Treatment Algorithm

1. Initial Assessment:

   • Determine frequency (≥2 migraines/month warrants prophylaxis)
   • Assess severity and disability
   • Evaluate comorbidities that may influence treatment choice

2. First-Line Selection Based on Comorbidities:

   • Hypertension → Propranolol, timolol, or candesartan
   • Overweight/obesity → Topiramate (weight loss benefit)
   • Depression/anxiety → Amitriptyline or venlafaxine
   • Epilepsy → Topiramate, valproate
   • Pregnancy (planning) → Avoid valproate and topiramate due to teratogenicity

3. Initiation and Titration:

   • Start at low dose and gradually titrate to effective dose
   • For topiramate: Begin with 25 mg/day, increase by 25-50 mg weekly to target 100 mg/day 4
   • For propranolol: Start at lower doses and gradually increase to 80-240 mg/day

4. Evaluation Period:

   • Allow 6-8 weeks at therapeutic dose before assessing efficacy
   • Target is ≥50% reduction in attack frequency

5. If Inadequate Response:

   • Switch to another first-line agent
   • If still inadequate, move to second-line options

Important Considerations and Pitfalls

• Medication overuse: Limit acute medications to ≤10 days/month for triptans and ≤15 days/month for NSAIDs to prevent medication overuse headache 1

• Pregnancy considerations: Valproate and topiramate should be avoided due to teratogenic effects. Acetaminophen is the safest acute option during pregnancy 1

• Drug interactions:

  • Propranolol may interact with statins and warfarin 2
  • Review current medications for potential interactions with migraine treatments

• Special populations:

  • In patients with diabetes, monitor blood glucose more frequently when initiating beta blockers or topiramate
  • In patients with renal impairment, use magnesium with caution 1

By following this evidence-based approach to migraine prophylaxis, clinicians can effectively reduce the frequency and severity of migraine attacks, improving patients' quality of life and reducing disability.