What are the first-line and second-line treatment options for migraine prophylaxis?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: June 3, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

First-line treatments for migraine prophylaxis include beta-blockers (propranolol 40-240 mg/day, metoprolol 50-200 mg/day), antiepileptics (topiramate 25-200 mg/day, valproate 500-1500 mg/day), and certain antidepressants (amitriptyline 10-150 mg/day). These medications are typically started at low doses and gradually increased over 4-8 weeks to minimize side effects. Treatment should continue for at least 3-6 months before assessing effectiveness, with success defined as a 50% reduction in migraine frequency.

Key Considerations

  • Second-line options include calcium channel blockers (verapamil 120-360 mg/day), angiotensin pathway modulators (candesartan 8-32 mg/day, lisinopril 10-20 mg/day), and newer CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) for refractory cases.
  • Medication choice should be individualized based on comorbidities, potential side effects, and patient preferences. For example, propranolol should be avoided in patients with asthma, while topiramate may benefit those with concurrent obesity.
  • Prophylactic treatment is generally recommended when patients experience four or more migraine days monthly, have significant disability despite acute treatments, or when acute medications are contraindicated or causing medication overuse headache, as noted in studies such as 1.

Treatment Approach

  • The treatment approach should involve educating patients about their condition and involving them in the management plan, as emphasized in 1.
  • Regular follow-up is necessary to assess the effectiveness of the treatment and to make adjustments as needed, considering the patient's response and any side effects, as discussed in 1.

From the Research

First-Line Treatment Options

  • Beta-blockers such as propranolol, timolol, and metoprolol are recommended as first-line agents for migraine prevention 2, 3, 4
  • Anticonvulsants like divalproex, sodium valproate, and topiramate are also considered first-line treatments 2, 3, 4
  • Amitriptyline is another first-line option, particularly useful in patients with comorbid tension-type headache, depression, and sleep disorders 5, 6, 3

Second-Line Treatment Options

  • Gabapentin and naproxen sodium have fair evidence of effectiveness and can be considered as second-line agents 2, 5
  • Venlafaxine, atenolol, and nadolol are probably effective but should be used as second-line therapy 4
  • Botulinum toxin has demonstrated fair effectiveness, but further studies are needed to define its role in migraine prevention 2
  • Other second-line options include lisinopril, candesartan, and magnesium, although evidence for these is limited 6, 4

Non-Pharmacological Treatments

  • Relaxation techniques, bio-feedback, cognitive behavioral therapy, and acupuncture are supported by some evidence and can be used as non-pharmacological treatments 5, 6, 4
  • Lifestyle modifications, such as maintaining a regular sleep schedule, meals, exercise, and stress management, are also important in migraine prevention 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 Headache Prophylaxis.

American family physician, 2019

Research

Migraine: prophylactic treatment.

The Journal of the Association of Physicians of India, 2010

Research

Update on the prophylaxis of migraine.

Current treatment options in neurology, 2008

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.