What are the first-line treatments for migraine prevention?

First-Line Treatments for Migraine Prevention

Beta blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate (100 mg/day), and candesartan are the recommended first-line medications for migraine prevention. 1, 2

Indications for Preventive Therapy

• Preventive therapy should be considered for patients who experience two or more migraine attacks per month with disability lasting 3 or more days per month 1, 2
• Patients who have contraindications to or failure of acute treatments should be evaluated for preventive therapy 1, 2
• Those using abortive medication more than twice per week should be considered for preventive treatment to avoid medication overuse headache 1, 2
• Patients with uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura, or migrainous infarction) are candidates for preventive therapy 1

First-Line Preventive Medications

Beta Blockers

• Propranolol (80-240 mg/day) and timolol (20-30 mg/day) have strong evidence for efficacy 1, 3
• Common side effects include dizziness, nausea, fatigue, depression, and insomnia, though these are generally well-tolerated 1
• Propranolol has demonstrated efficacy in reducing migraine frequency in controlled trials 3

Topiramate

• Recommended dose is 100 mg/day (typically 50 mg twice daily) 1, 4, 5
• Clinical trials show topiramate reduces migraine days by approximately two per month 6
• Most common side effects include paresthesia (51% at 100 mg/day), fatigue, decreased appetite, and cognitive difficulties 4, 5
• Particularly beneficial for patients concerned about weight gain, as it is often associated with weight loss 5
• Efficacy has been demonstrated even in chronic migraine with medication overuse 7

Candesartan

• Emerging evidence supports candesartan as a first-line agent 1
• Particularly useful for patients with comorbid hypertension 1

Second-Line Preventive Medications

• Amitriptyline (30-150 mg/day) is recommended as a second-line agent 1

• May be particularly effective in patients with mixed migraine and tension-type headache 1

• Common side effects include weight gain, drowsiness, and anticholinergic symptoms 1

• Flunarizine (not available in the US) is a second-line option where available 1

• Sodium valproate (800-1500 mg/day) or divalproex sodium (500-1500 mg/day) are second-line options 1

  • These are strictly contraindicated in women of childbearing potential due to teratogenic effects 1
  • Side effects include hair loss, tremor, and weight gain 1

Third-Line Preventive Medications

• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) are recommended as third-line agents 1
• In Europe, these are restricted to patients in whom other preventive medications have failed 1
• OnabotulinumtoxinA (Botox) is FDA-approved for chronic migraine prevention in adults with 15 or more headache days per month 8

Implementation of Preventive Therapy

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 1, 2
• Allow an adequate trial period of 2-3 months before determining efficacy 1, 2
• Monitor for medication overuse, which can interfere with preventive treatment 2
• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 2

Common Pitfalls to Avoid

• Failing to recognize medication overuse headache from frequent use of acute medications 2
• Inadequate duration of preventive trial (less than 2-3 months) 2
• Starting with too high a dose, leading to poor tolerability and discontinuation 1
• Not addressing comorbidities that may influence treatment selection (e.g., avoiding valproate in women of childbearing potential) 1

Non-Pharmacological Options

• Consider neuromodulatory devices, biobehavioral therapy, or acupuncture as adjuncts to medication or as stand-alone treatments when medications are contraindicated 1
• Limited evidence exists for physical therapy, spinal manipulation, and dietary approaches 1