What is the best medication for migraine prevention?

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Last updated: June 4, 2025View editorial policy

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From the Guidelines

The most effective medication for migraine prevention is erenumab, fremanezumab, or galcanezumab, as recommended by the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline for the management of headache 1.

Migraine Prevention Medications

The choice of medication depends on the individual's specific migraine pattern, medical history, potential side effects, and insurance coverage.

  • First-line preventive medications include beta-blockers (propranolol 40-240 mg daily or metoprolol 50-200 mg daily), anticonvulsants (topiramate 25-100 mg twice daily or valproate 250-500 mg twice daily), and certain antidepressants (amitriptyline 10-150 mg at bedtime).
  • CGRP monoclonal antibodies like erenumab (70-140 mg monthly), fremanezumab (225 mg monthly), or galcanezumab (120 mg monthly after loading dose) are newer options with fewer side effects.

Key Considerations

  • Prevention should be started at a low dose and gradually increased, with treatment typically continued for 3-6 months before evaluating effectiveness.
  • Preventive medication is generally recommended when you experience four or more migraine days monthly, significant disability despite acute treatment, or when acute medications aren't effective or can't be used.
  • These medications work by stabilizing neuronal excitability, reducing inflammation, or blocking pain pathways involved in migraine development, as discussed in the American College of Physicians clinical guideline for the prevention of episodic migraine headache 1.

From the Research

Migraine Prevention Medications

The following medications are considered effective for migraine prevention:

  • Topiramate: studies have shown that topiramate is an effective option for adults who require migraine prophylaxis, with a dosage of 100 mg/day being the most effective in terms of efficacy and tolerability 2, 3, 4
  • Propranolol: considered a first-line agent for migraine prevention, with sufficient evidence and consensus to support its use 5, 6
  • Amitriptyline: a first-line agent for migraine prevention, with sufficient evidence and consensus to support its use 5, 6
  • Divalproex: a first-line agent for migraine prevention, with sufficient evidence and consensus to support its use 5, 6
  • Valproate: a first-line agent for migraine prevention, with sufficient evidence and consensus to support its use 5, 6

Comparison of Medications

Studies have compared the efficacy of different medications for migraine prevention, including:

  • Topiramate vs. propranolol: topiramate has been shown to be an effective option for migraine prevention, with a similar reduction in migraine frequency to propranolol 2, 3
  • Topiramate vs. other preventive agents: the efficacy of topiramate is comparable to other first-line drugs, but there are no published trials with a superiority design to establish its role in the available therapeutic armamentarium 4

Side Effects and Considerations

The following side effects and considerations should be taken into account when using medications for migraine prevention:

  • Topiramate: common side effects include paresthesia, cognitive dysfunction, and weight loss, with a dose-related increase in paresthesia 2, 3
  • Propranolol: common side effects include fatigue, dizziness, and nausea 5
  • Amitriptyline: common side effects include drowsiness, dry mouth, and constipation 5
  • Divalproex: common side effects include nausea, vomiting, and dizziness 5
  • Valproate: common side effects include nausea, vomiting, and dizziness 5

Dosage and Administration

The following dosages and administration schedules are recommended for medications used in migraine prevention:

  • Topiramate: 100 mg/day, with a gradual increase in dosage to minimize side effects 2, 3
  • Propranolol: 80-240 mg/day, with a gradual increase in dosage to minimize side effects 5
  • Amitriptyline: 25-100 mg/day, with a gradual increase in dosage to minimize side effects 5
  • Divalproex: 500-1000 mg/day, with a gradual increase in dosage to minimize side effects 5
  • Valproate: 500-1000 mg/day, with a gradual increase in dosage to minimize side effects 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Topiramate for migraine prevention.

Pharmacotherapy, 2006

Research

Clinical pharmacology of topiramate in migraine prevention.

Expert opinion on drug metabolism & toxicology, 2011

Research

Medications for migraine prophylaxis.

American family physician, 2006

Research

Migraine: prophylactic treatment.

The Journal of the Association of Physicians of India, 2010

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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