What are the first-line treatment options for migraines prophylaxis?

Migraine Prophylaxis Treatment

First-Line Medications

Beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate (100 mg/day), and candesartan are the first-line prophylactic medications for migraine prevention. 1

Beta-Blockers

• Propranolol (80-240 mg/day) and timolol (20-30 mg/day) have the strongest evidence for efficacy and are FDA-approved for migraine prophylaxis 1, 2
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol if propranolol is not tolerated 1
• Propranolol is particularly useful for patients with comorbid hypertension or anxiety 2

Topiramate

• Target dose is 100 mg/day (typically 50 mg twice daily), which provides optimal efficacy without the increased side effects seen at 200 mg/day 1, 3, 4
• Start at 25 mg/day and titrate by 25-50 mg weekly to minimize adverse effects 5
• Topiramate is especially preferred for patients concerned about weight gain or who are currently overweight, as weight loss is a common side effect 3, 5
• Efficacy can be seen as early as the first month of treatment, though full evaluation requires 2-3 months 5
• Most common side effects are paresthesia (dose-related), fatigue, decreased appetite, nausea, and cognitive dysfunction 3, 4
• Topiramate is effective even in chronic migraine (≥15 headache days/month) and in the presence of medication overuse, reducing migraine days by 3.5 per month 6

Candesartan

• Candesartan is a first-line agent particularly useful for patients with comorbid hypertension 1
• This ARB provides dual benefit for both blood pressure control and migraine prevention 1

Second-Line Medications

Amitriptyline

• Amitriptyline (30-150 mg/day) is a second-line agent particularly effective in patients with mixed migraine and tension-type headache 1, 7
• Consider this option when first-line agents fail or when comorbid depression or insomnia is present 1

Valproate/Divalproex

• Sodium valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) are second-line options 1, 7
• These agents are strictly contraindicated in women of childbearing potential due to teratogenic effects 1

Indications for Preventive Therapy

Initiate prophylaxis when patients meet any of these criteria:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 1, 7
• Using acute/abortive medications more than twice per week (to prevent medication overuse headache) 1, 7
• Contraindications to or failure of acute treatments 1, 7
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 1

Implementation Strategy

Titration and Trial Period

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 1, 7
• Allow an adequate trial period of 2-3 months before determining efficacy for oral agents 1, 7
• For CGRP monoclonal antibodies, efficacy should be assessed only after 3-6 months 1

Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 1, 7
• Monitor for medication overuse, which can interfere with preventive treatment 1, 7
• Screen for medication overuse headache if patients use acute medications more than twice weekly 1

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

Third-Line Options

When first- and second-line agents fail or are contraindicated:

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered 1
• These require 3-6 months for efficacy assessment 1

Non-Pharmacological Adjuncts

• Neuromodulatory devices can be considered as adjuncts or stand-alone treatments when medications are contraindicated 1
• Biobehavioral therapy (biofeedback, relaxation training) can be used as adjunct or stand-alone treatment 1
• Acupuncture may be considered, though not superior to sham acupuncture in controlled trials 1

Critical Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications (more than twice weekly) 1, 7
• Inadequate duration of preventive trial (less than 2-3 months) before declaring treatment failure 1, 7
• Starting with too high a dose, leading to poor tolerability and discontinuation 1
• Prescribing valproate to women of childbearing potential without addressing contraception 1
• Allowing patients to increase frequency of acute medication use in response to treatment failure, creating a vicious cycle of medication overuse headache 8