What are the second-line therapies for migraine prevention?

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From the Guidelines

Second-line therapies for migraine prevention should include CGRP monoclonal antibodies such as erenumab, fremanezumab, or galcanezumab, as they have shown strong evidence for preventing episodic or chronic migraine 1. When considering second-line options, it's essential to evaluate the patient's specific needs and medical history. Other alternatives may include:

  • Topiramate, which has shown weak evidence for preventing episodic and chronic migraine 1
  • Propranolol, a beta-blocker with weak evidence for migraine prevention 1
  • Valproate, which has weak evidence for preventing episodic migraine 1
  • OnabotulinumtoxinA injections, which have weak evidence for preventing chronic migraine 1
  • Lisinopril, an angiotensin pathway blocker with weak evidence for migraine prevention 1
  • Candesartan or telmisartan, which have strong evidence for preventing episodic migraine but may not be considered second-line due to their first-line recommendation 1 It's crucial to note that the choice of second-line therapy should be individualized, taking into account the patient's response to previous treatments, potential side effects, and comorbidities. Key considerations when initiating preventive therapy include:
  • Starting with a low dose and gradually increasing to minimize side effects
  • Allowing at least 2-3 months of treatment at an adequate dose to assess efficacy
  • Monitoring for potential interactions with other medications and adjusting the treatment plan as needed.

From the Research

Second-Line Therapies for Migraine Prevention

The following are considered second-line therapies for migraine prevention:

  • Venlafaxine, gabapentin, naproxen, butterbur root, riboflavin, and magnesium, which have less efficacy and evidence compared to first-line agents 2
  • Dihydroergotamine and valproic acid, which have some data supporting efficacy as second-line therapy in the emergency department setting 3
  • Greater occipital nerve blocks (GONBs), which have been shown to be efficacious as a second-line treatment option 3
  • Injectable non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, which can be used as second-line therapy for patients who fail to improve after treatment with first-line medication 3

Considerations for Second-Line Therapy

When considering second-line therapies for migraine prevention, it is essential to take into account the patient's individual characteristics, such as co-morbidity, side effects, and treatment history 2, 4. The choice of second-line therapy should be based on the available evidence and the patient's specific needs.

Emerging Therapies

Newer therapies, such as monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor, have shown high efficacy and are currently recommended for use if two traditional preventive therapies have proven inadequate 4. Oral CGRP receptor antagonists (gepants) are also being tested for migraine prevention 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Migraine: prophylactic treatment.

The Journal of the Association of Physicians of India, 2010

Research

Preventive Migraine Treatment.

Continuum (Minneapolis, Minn.), 2021

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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