What preventative medication is recommended for a patient with frequent or severe migraine attacks?

Preventative Medication for Migraine

For patients with frequent or severe migraines (≥2 attacks per month with significant disability, or using acute medications >2 days per week), initiate preventive therapy with propranolol 80-240 mg/day, timolol 20-30 mg/day, topiramate 50-100 mg/day, or candesartan as first-line options, with selection based on comorbidities and side effect profiles. 1

Indications for Preventive Therapy

Preventive therapy should be initiated when patients meet any of the following criteria:

• Two or more migraine attacks per month producing disability lasting 3 or more days per month 1
• Using acute medications more than twice per week (>10 days per month for triptans, >15 days per month for NSAIDs), which risks medication-overuse headache 1
• Contraindication to or failure of acute treatments, making attack management inadequate 1
• Uncommon migraine conditions such as hemiplegic migraine, migraine with prolonged aura, or migrainous infarction 1
• Patient preference when quality of life is significantly impaired despite optimized acute therapy 1

First-Line Preventive Medications

Beta-Blockers (Preferred for Patients with Hypertension or Anxiety)

• Propranolol 80-240 mg/day has the strongest evidence for efficacy and is FDA-approved for migraine prevention 1
• Timolol 20-30 mg/day is equally effective with strong evidence 1
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol, though with slightly less robust evidence 1
• Contraindications: Avoid in patients with asthma, heart block, or those who practice competitive sports 1

Topiramate (Preferred for Patients with Obesity)

• Topiramate 50-100 mg/day (typically 50 mg twice daily) is first-line with strong evidence for efficacy 1
• Start low (25 mg daily) and titrate slowly over 4-8 weeks to minimize side effects, particularly cognitive symptoms and paresthesias 1, 2
• Associated with weight loss, making it advantageous for patients with obesity 1
• Contraindications: Use caution in patients with kidney stones or glaucoma 1

Candesartan (Preferred for Patients with Hypertension)

• Candesartan is recommended as first-line, particularly useful for patients with comorbid hypertension 1
• Provides dual benefit of blood pressure control and migraine prevention 1

Second-Line Preventive Medications

Amitriptyline (Preferred for Patients with Depression, Anxiety, or Mixed Headache Types)

• Amitriptyline 30-150 mg/day is effective for patients with mixed migraine and tension-type headache or comorbid depression 1
• Start at 10-25 mg at bedtime and titrate slowly to minimize anticholinergic side effects 1
• Side effects include sedation, dry mouth, weight gain, and constipation 1

Valproate/Divalproex (Use with Extreme Caution)

• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day are effective second-line options 1
• Absolutely contraindicated in women of childbearing potential due to severe teratogenic effects 1
• Side effects include weight gain, hair loss, tremor, and hepatotoxicity 1

Flunarizine (Where Available)

• Flunarizine 5-10 mg once daily at night is an effective second-line agent with efficacy comparable to propranolol and topiramate 1
• Contraindications: Active Parkinsonism, history of extrapyramidal disorders, or current depression 1
• Avoid in elderly patients due to increased risk of extrapyramidal symptoms and depression 1
• Common side effects include sedation, weight gain, and daytime tiredness 1

Third-Line: CGRP Monoclonal Antibodies (For Treatment-Resistant Cases)

• Erenumab, fremanezumab, or galcanezumab administered monthly via subcutaneous injection should be considered when patients have failed 2-3 oral preventive medications 1
• Efficacy assessment requires 3-6 months of treatment before determining effectiveness 1
• Erenumab 70 mg or 140 mg monthly reduces migraine days by approximately 2.5 days per month in chronic migraine 3
• Galcanezumab 120 mg monthly (with 240 mg loading dose) reduces migraine days by approximately 2 days per month in episodic migraine 4
• Significantly more expensive than oral agents, with annualized costs of $5,000-$6,000 1

Implementation Strategy

Starting and Titrating Preventive Therapy

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 1
• Allow an adequate trial period of 2-3 months before assessing efficacy, as most oral preventives require this duration to demonstrate benefit 1
• Use headache diaries to track attack frequency, severity, duration, disability, and treatment response 1
• Success is defined as ≥50% reduction in monthly migraine days, though even 30-40% reduction can be clinically meaningful 1

Duration of Therapy

• Continue successful preventive therapy for 6-12 months, then consider tapering to determine if it can be discontinued 1
• Some patients may require long-term or indefinite preventive therapy if migraines recur after discontinuation 1

Critical Pitfalls to Avoid

• Do not fail to recognize medication-overuse headache from frequent use of acute medications (≥10 days/month for triptans, ≥15 days/month for NSAIDs), which can interfere with preventive treatment effectiveness 1
• Do not conduct inadequate duration of preventive trial (less than 2-3 months), as premature discontinuation may miss therapeutic benefit 1
• Do not start with too high a dose, leading to poor tolerability and discontinuation—always start low and titrate slowly 1
• Do not prescribe valproate to women of childbearing potential due to severe teratogenic risk 1
• Do not ignore comorbidities that may influence treatment selection, such as using beta-blockers for patients with hypertension or amitriptyline for those with depression 1

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, and relaxation training should be offered alongside medication as effective adjuncts 1
• Neuromodulatory devices can be considered as adjuncts or stand-alone treatments when medications are contraindicated 1
• Acupuncture may be considered, though evidence shows it is not superior to sham acupuncture in controlled trials 1
• Lifestyle modifications including sleep hygiene, regular meals, hydration, and stress management should be addressed 1