What are the recommended prophylactic medications for migraine?

Prophylactic Medications for Migraine

First-Line Prophylactic Agents

Beta-blockers, topiramate, and candesartan are the first-line medications for migraine prophylaxis, with propranolol (80-240 mg/day) and timolol (20-30 mg/day) having the strongest evidence for efficacy. 1

Beta-Blockers

• Propranolol (80-240 mg/day) is FDA-approved and carries the strongest evidence for migraine prevention 1
• Timolol (20-30 mg/day) is equally effective as first-line therapy 1
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol if propranolol is not tolerated 1

Topiramate

• Target dose is 100 mg/day (typically 50 mg twice daily), with no additional benefit observed at 200 mg/day 1, 2
• Start at 25 mg daily and increase by 25 mg weekly to minimize side effects 1
• Efficacy can be observed as early as the first month, though a 2-3 month trial is recommended before determining effectiveness 1, 3
• Most common side effects include paresthesia (48%), weight loss (50%), fatigue, decreased appetite, and cognitive disturbances (20%) 2, 4
• Particularly advantageous for patients concerned about weight gain or who are currently overweight 2

Candesartan

• Recommended as first-line therapy, especially useful for patients with comorbid hypertension 1

Second-Line Prophylactic Agents

Amitriptyline

• Dose range: 30-150 mg/day 1
• Particularly effective for patients with mixed migraine and tension-type headache 1

Valproate/Divalproex Sodium

• Sodium valproate: 800-1500 mg/day 1
• Divalproex sodium: 500-1500 mg/day 1
• Strictly contraindicated in women of childbearing potential due to teratogenic effects 1
• Common side effects include weight gain (24%), hair loss (24%), tremor, and gastrointestinal symptoms (24%) 4

Flunarizine

• Effective second-line option where available 1

Third-Line Agents: CGRP Monoclonal Antibodies

CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) should be considered when first- and second-line preventive treatments have failed or are contraindicated. 1

• Require 3-6 months of treatment before assessing efficacy (longer than oral agents) 1
• Strong evidence supports their use for both episodic and chronic migraine prevention 1

Indications for Preventive Therapy

Preventive therapy should be initiated for patients experiencing ≥2 migraine attacks per month with disability lasting ≥3 days per month. 1

Additional indications include:

• Using acute medications more than twice per week (to prevent medication overuse headache) 1
• Contraindications to or failure of acute treatments 1
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 1

Implementation Strategy

Titration and Trial Period

• Start with low doses and titrate slowly until clinical benefits are achieved or side effects limit further increases 1
• Allow 2-3 months for oral agents before determining efficacy 1
• CGRP monoclonal antibodies require 3-6 months for adequate assessment 1

Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 1
• Monitor for medication overuse, which can interfere with preventive treatment effectiveness 1

Duration of Therapy

• Consider tapering or discontinuing preventive treatment after 6-12 months of successful therapy 1
• A useful measure of success is calculating the percentage reduction in monthly migraine days 1

Critical Pitfalls to Avoid

• Do not fail to recognize medication overuse headache from frequent use of acute medications (>2 days/week) 1
• Avoid inadequate trial duration (less than 2-3 months for oral agents) 1
• Do not start with excessively high doses, which leads to poor tolerability and discontinuation 1
• Never prescribe valproate/divalproex to women of childbearing potential 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) serves as effective adjunctive treatment 1
• Acupuncture may be considered, though not superior to sham acupuncture in controlled trials 1