New ACP Guideline on Migraine Prevention, Shows No Clinically Important Advantages for Newer, Expensive Medications

PHILADELPHIA Feb. 4, 2025 – The American College of Physicians (ACP) has developed new recommendations to prevent episodic migraines in nonpregnant adults in outpatient settings. Prevention of Episodic Migraine Headache using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline from the American College of Physicians was published today in Annals of Internal Medicine.

Migraine is characterized by recurrent episodes of usually moderate-to-severe intensity headache lasting 4 to 72 hours with or without sensory disturbances, generally pulsating and often accompanied by nausea, vomiting, or aversion to light or sound. Because the condition remains under-diagnosed and under-treated, only a small percentage of eligible people receive preventive pharmacologic treatments.

ACP considered the findings from an accompanying comparative effectiveness systematic review that used the GRADE approach to analyze the effects of pharmacologic treatment to prevent episodic migraine headache on the following outcomes: migraine frequency and duration, number of days medication was taken for acute treatment of migraine, frequency of migraine-related emergency room visits, migraine-related disability, quality of life and physical function, and discontinuations due to adverse events. Additional data about adverse events were identified through Food and Drug Administration medication labels and eligible studies.

In this guideline, ACP makes 3 Recommendations. In Recommendation 1, ACP suggests clinicians initiate monotherapy to prevent episodic migraine headache in nonpregnant adults in outpatient settings by choosing one of the following pharmacologic treatments: a beta-adrenergic blocker, either metoprolol or propranolol; the antiseizure medication valproate; the serotonin and norepinephrine reuptake inhibitor venlafaxine; or the tricyclic antidepressant amitriptyline. In Recommendation 2, if nonpregnant adults in outpatient settings do not tolerate or inadequately respond to a trial or trials of treatments in Recommendation 1, then ACP suggests that clinicians use monotherapy with a calcitonin gene-related peptide (CGRP) antagonist (atogepant or rimegepant) or a CGRP monoclonal antibody (eptinezumab, erenumab, fremanezumab, or galcanezumab) to prevent episodic migraine headache. In Recommendation 3, if nonpregnant adults in outpatient settings still do not tolerate or inadequately respond to a trial or trials of treatments suggested in Recommendations 1 and 2, then ACP suggests clinicians use monotherapy with the antiseizure medication topiramate to prevent episodic migraine headache.

Because of the lack of differences in clinical net benefit between virtually all treatments, the CGC used economic evidence and patients’ values and preferences data as primary factors in prioritizing different migraine prevention treatments. The median annual costs of recommended initial oral treatments varied substantially.

ACP recently published Incorporating Economic Evidence in Clinical Guidelines which is a framework for standardizing the approach to identifying, appraising, and considering economic evidence in the development of ACP clinical guidelines, in recognition of accelerating health care costs and the impact on patients. 

Recognizing that the actual cost of treatment for people may vary, it is important for physicians to carefully assess each person’s economic circumstances and preferences during the decision-making process when choosing the most appropriate treatment, for example the preference of oral vs. injectable medications.

“This guideline assessed the comparative effectiveness of medications to help clinicians select which medications to use for prevention of episodic migraine and will be of great value to internal medicine physicians who are on the frontline of treating patients suffering from these types of migraines,” said Isaac O. Opole, president, ACP. “Based on the evidence of the clinical recommendation, we can then take into consideration cost and personal preference in prevention treatment choices. These recommendations will be critical in helping physicians and other clinical staff to treat their patients with episodic migraine, ultimately supporting them in the prescribing process and contributing to patients’ improved wellbeing.”

The guideline emphasizes that a patient’s adherence to pharmacologic treatment is crucial because improvement may occur gradually after initiating a long-term treatment option for preventing episodic migraine, with an effect that may become apparent after the first few weeks of treatment.

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About the American College of Physicians
The American College of Physicians is the largest medical specialty organization in the United States with members in more than 172 countries worldwide. ACP membership includes 161,000 internal medicine physicians, related subspecialists, and medical students. Internal medicine physicians are specialists who apply scientific knowledge and clinical expertise to the diagnosis, treatment, and compassionate care of adults across the spectrum from health to complex illness. Follow ACP on XFacebookInstagram and LinkedIn.

Contact: Laura Baldwin, 215 351 2668,  lbaldwin@acponline.org