National Headache Foundation Response to American College of Physicians Migraine Headache Guidelines

Download the National Headache Foundation's full Response Statement above.

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In February 2025, the American College of Physicians (ACP) published a featured article titled, “Prevention of Episodic Migraine Headache Using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline from the American College of Physicians,” in its journal Annals of Internal Medicine.¹ According to the ACP, the guidelines were developed to identify which pharmacologic treatments for acute episodic migraine should be prioritized based on a comparison of harms and benefits, patient preferences, and economic considerations.

Since publication, these guidelines have generated significant debate and criticism from headache and migrain specialists, especially with respect to recommendations regarding the use of the antiseizure medication valproate and calcitonin gene-related peptide (CGRP)–targeting therapies. Members of the National Headache Foundation (NHF) Scientific Committee met to discuss the guidelines and released a response statement available on www.practicalneurology.com and on the NHF’s website (https://headaches.org/nhf-response-acp-guideline-prevention-episodic-migraine/). Below is a summary of the main points covered in the NHF statement.

Concerns Regarding Recommendations for Women of Reproductive Age

A primary concern was the ACP’s recommendation of the use of valproate as a first-line migraine treatment despite the medication’s well-documented teratogenic effects and side effect profile. The NHF highlights risks for women of reproductive age who may become pregnant while using valproate.

Use of Non–Migraine-Specific First-Line Pharmacologic Agents

The ACP’s guideline recommends the use of non–migraine-specific medications for first-line treatment over newer, migraine-specific preventive treatments, specifically CGRP-targeting medications. In their response statement, the NHF cited evidence demonstrating that CGRP antagonists may have less frequent and more tolerable side effects compared with non–migraine-specific medications such as divalproex and topiramate. Additionally, CGRP-targeting therapies may have better long-term compliance. The NHF urges the ACP to reconsider CGRP-targeting therapies as first-line treatment options. Additionally, they recommend moving divalproex to a lower tier behind other medications like topiramate, due to weight gain associated with its use.

Lack of Headache Specialists in “Topic Expert Panel”

The ACP’s guideline was developed through a systematic review conducted by the organization’s Clinical Guidelines Committee, comprising a team of internal medicine physicians. In their response statement, the NHF expressed concern about the lack of information available on the therapeutic area of expertise of participants on the Clinical Guideline Committee. It is unclear whether the guideline authors have sufficient experience in migraine management, according to the NHF.

Overemphasis of Cost Over Clinical Efficacy and Safety

In their response statement, the NHF questioned the ACP’s prioritization of cost over compliance and tolerability for patients in the guidelines. The ACP noted that, if cost was not a factor, CGRP-targeting therapies would be recommended as a first-line therapy. The NHF questioned this decision as well as the recommendation of topiramate as a third-line treatment behind valproate, despite the latter’s greater risk profile. The NHF suggests that the ACP recategorize topiramate as a first-line preventive therapy for migraine.

Negative Impact on Insurance Coverage for CGRP Antagonist Gepants and Monoclonal Antibody Therapies

The NHF warned that the ACP’s decision to not recommend CGRP-targeted therapies, including gepants and monoclonal antibodies, as first-line treatments may impact future decisions made by insurers. Insurance providers may cite the published ACP guideline in decisions to deny coverage for CGRP therapies, requiring patients to try and fail less effective, non–Migraine-Specific options, which would delay appropriate care.

Reliance on Low-Certainty Evidence

The NHF expressed concern about the ACP’s decision to base their guideline on “low-certainty evidence,” which may limit clinical applicability. Although CGRP-targeting therapies are not recommended as a first-line option by the ACP, they are supported by robust clinical trial data.

Disregard for American Headache Society Guidelines

The final concern noted by the NHF is the ACP’s decision not to incorporate the recent consensus position statement of the American Headache Society on CGRP-targeting therapies in their guideline. This consensus statement, titled “Calcitonin Gene-Related Peptide-Targeting Therapies Are a First-Line Option for the Prevention of Migraine: An American Headache Society Position Statement Update” and published in Headache, constitutes a comprehensive set of recommendations based on a review of all preventive options, and the omission of these recommendations, according to the NHF, weakens the credibility of the ACP’s guideline.²

Members of the NHF committee include Vincent Martin, MD—NHF Board President; Fred Cohen, MD; Merle Diamond, MD; Jaclyn R. Duvall, MD; Mark Green, MD; Paul G. Mathew, MD; Hope O’Brien, MD; and Timothy R. Smith, MD.

The views and opinions expressed in this article do not reflect the views and opinions of Practical Neurology, Bryn Mawr Communications, and/or US HealthConnect.