What are the recommended treatments for migraine prevention?

Migraine Prevention: Recommended Treatments

For migraine prevention, start with propranolol (80-240 mg/day), timolol (20-30 mg/day), topiramate (100 mg/day), or candesartan as first-line agents, reserving CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) for patients who fail or cannot tolerate these initial options. 1

Indications for Starting Preventive Therapy

Initiate preventive therapy when patients meet any of these criteria:

• ≥2 migraine attacks per month with disability lasting ≥3 days per month 1
• Using abortive 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, or migrainous infarction 1

First-Line Preventive Medications

Beta-Blockers

• Propranolol 80-240 mg/day or timolol 20-30 mg/day have the strongest evidence for efficacy 1
• Alternative beta-blockers include atenolol, bisoprolol, or metoprolol 1
• Particularly useful for patients with comorbid hypertension or anxiety 1

Topiramate

• Target dose: 100 mg/day (typically 50 mg twice daily) 1
• Start low and titrate by 25 mg weekly to minimize side effects 2, 3
• Especially appropriate for patients concerned about weight gain or who are overweight (causes weight loss) 2
• Most common side effects: paresthesia (35-51%), fatigue, decreased appetite, nausea 2, 4
• Critical caveat: Cognitive dysfunction can occur; warn patients about difficulty with concentration and word-finding 4
• Effective even in chronic migraine (≥15 headache days/month) and medication overuse headache 5

Candesartan

• First-line agent, particularly for patients with comorbid hypertension 1
• Well-tolerated alternative when beta-blockers are contraindicated 1

Second-Line Preventive Medications

Amitriptyline

• Dose: 30-150 mg/day 1
• Particularly effective for patients with mixed migraine and tension-type headache 1
• Useful when insomnia is a comorbidity 1

Valproate/Divalproex Sodium

• Dose: 800-1500 mg/day (valproate) or 500-1500 mg/day (divalproex) 1
• Strictly contraindicated in women of childbearing potential due to teratogenic effects 1
• This is a hard stop—do not prescribe to any woman who could become pregnant 1

Flunarizine

• Effective second-line option where available (not available in the US) 1

Third-Line: CGRP Monoclonal Antibodies

Reserve for patients who have failed or cannot tolerate first- and second-line options:

• Erenumab, fremanezumab, or galcanezumab have strong evidence for episodic or chronic migraine prevention 1
• Eptinezumab (IV) has weaker evidence 1
• Require 3-6 months to assess efficacy (longer than oral agents) 1
• Significantly more expensive than traditional preventives 1

Implementation Strategy

Dosing Approach

• Start low, titrate slowly until clinical benefits achieved or side effects limit increases 1
• Allow an adequate trial period of 2-3 months before determining efficacy for oral agents 1
• For CGRP antibodies, assess efficacy only after 3-6 months 1

Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 1
• Calculate percentage reduction in monthly migraine days to quantify success 1
• A ≥50% reduction in attack frequency is considered successful 6

Duration of Therapy

• After 6-12 months of successful therapy, consider pausing preventive treatment to determine if it can be discontinued 1
• Many patients can successfully taper off after achieving sustained control 1

Critical Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent acute medication use (≥10 days/month for triptans, ≥15 days/month for NSAIDs) 1
• Inadequate trial duration (less than 2-3 months for oral agents) before declaring treatment failure 1
• Starting with too high a dose, leading to poor tolerability and discontinuation 1
• Prescribing valproate to women of childbearing potential—this is teratogenic and absolutely contraindicated 1
• Not addressing comorbidities that influence treatment selection (e.g., hypertension favors candesartan, insomnia favors amitriptyline) 1

Non-Pharmacological Adjuncts

Consider as adjuncts to medication or stand-alone treatments when medications are contraindicated:

• Neuromodulatory devices 1
• Biobehavioral therapy (biofeedback, relaxation training) 1, 6
• Acupuncture (though not superior to sham acupuncture in controlled trials) 1
• Limited evidence exists for physical therapy, spinal manipulation, and dietary approaches 1

Special Populations

Chronic Migraine (≥15 headache days/month)

• OnabotulinumtoxinA is recommended specifically for chronic migraine prevention, not episodic migraine 1
• Requires 6-9 months to assess efficacy 6
• Serious risks: problems with swallowing, speaking, or breathing; spread of toxin effects can cause botulism-like symptoms 7

Patients with Medication Overuse

• Topiramate remains effective even in the presence of medication overuse 5
• Address overuse pattern while initiating preventive therapy 1