What are the first-line medications for migraine prevention?

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From the Guidelines

The first-line medications for migraine prevention are propranolol (80 to 240 mg/d), timolol (20 to 30 mg/d), amitriptyline (30 to 150 mg/d), divalproex sodium (500 to 1500 mg/d), and sodium valproate (800 to 1500 mg/d). These medications are recommended for patients who experience two or more attacks per month that produce disability lasting 3 or more days per month, have a contraindication to or failure of acute treatments, use abortive medication more than twice per week, or have uncommon migraine conditions such as hemiplegic migraine, migraine with prolonged aura, or migrainous infarction 1. Key considerations for selecting a preventive therapy include the patient's comorbidities, potential side effects, and individual factors.

  • Beta-blockers like propranolol and timolol are effective but should be used with caution in patients with certain medical conditions.
  • Antiepileptic drugs such as divalproex sodium and sodium valproate are also effective options.
  • Amitriptyline, an antidepressant, is another first-line option for migraine prevention. It is essential to educate patients about the control of acute attacks and preventive therapy and engage them in the formulation of a treatment plan 1. Treatment should be started at a low dose and gradually increased over time to minimize side effects, and preventive therapy should continue for at least 3-6 months before reassessing effectiveness.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

First-Line Medications for Migraine Prevention

The following medications are considered first-line treatments for migraine prevention:

  • Propranolol 2, 3, 4, 5
  • Timolol 2, 4
  • Amitriptyline 2, 3, 4, 5
  • Divalproex 2, 4
  • Sodium valproate 2, 4
  • Topiramate 2, 3, 4, 5
  • Flunarizine 3, 5
  • Valproic acid 3

Second-Line Medications for Migraine Prevention

The following medications are considered second-line treatments for migraine prevention:

  • Gabapentin 2, 3, 4, 5
  • Naproxen sodium 2
  • Venlafaxine 3, 5
  • Butterbur root 3, 5
  • Vitamin B2 (riboflavin) 2, 3, 4, 5
  • Magnesium 2, 3, 4, 5
  • Botulinum toxin 2 (although its role in migraine prevention is still being studied)

Principles of Preventive Treatment

The choice of preventive treatment for migraine should be based on the presence of comorbid and coexistent illness, patient preference, reproductive potential and planning, and best available evidence 4. Treatment efficacy should be assessed after 2 or 3 months, and in case of failure or poor tolerance, another treatment should be started 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Medications for migraine prophylaxis.

American family physician, 2006

Research

Preventive Migraine Treatment.

Continuum (Minneapolis, Minn.), 2015

Research

Migraine: prophylactic treatment.

The Journal of the Association of Physicians of India, 2010

Research

[Prophylactic drug treatment of migraine].

Revue neurologique, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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