New ACP Guidelines Recommend Adding Triptan to NSAID or Acetaminophen for Migraines

The American College of Physicians (ACP) now recommends adding a triptan to nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen to treat moderate to severe acute episodic migraine headache.1

Announced on March 17, 2025, the ACP released new recommendations for treating acute episodic migraines in nonpregnant adults in outpatient settings, published in the Annals of Internal Medicine. The updated guidelines are based on ACP’s evaluation of migraine pharmacologic treatments.

“Comparative effectiveness evidence showed that the combination of a triptan (sumatriptan) and an NSAID (naproxen) had the greatest net benefit, with a larger net benefit than monotherapy with a triptan (moderate-certainty evidence), an NSAID (aspirin, celecoxib, diclofenac, ibuprofen, or naproxen; high-certainty evidence), acetaminophen (low-certainty evidence), or a CGRP antagonist-gepant (low-certainty evidence),” ACP wrote in a statement.

Migraine, characterized by recurrent episodes of a moderate to severe headache lasting 4 to 72 hours, can occur with or without sensory disturbances. Patients may experience nausea, vomiting, or aversion to light or sound. Migraine is often underdiagnosed and undertreated.

ACP examined strong evidence on the comparative effectiveness of migraine pharmacologic treatments, focusing on benefits and harms, patient values and preferences, and the economy. They examined the treatments of acetaminophen, imegepant, ubrogepant, zavegepant, Lasmiditan, dihydroergotamine (mesylate), aspirin, celecoxib, diclofenac potassium, ibuprofen, naproxen, almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan. They hoped to prioritize the most effective migraine treatment.

The guidelines present 2 new recommendations: adding triptan to unresponsive NSAIDs or acetaminophen to treat moderate to severe acute episodic migraine headache in outpatient settings for nonpregnant adults. Patients on combination therapy had a greater likelihood of sustained pain relief up to 48 hours after initial treatment and a lower likelihood of using rescue medication at 24 hours.

ACP also recommends clinicians to consider counseling their patients to initiate combination therapy—a triptan with NASAID or acetaminophen—as soon as possible after the onset of acute migraine headache.

The ACP had previously published a companion guideline, Prevention of Episodic Migraine Headache using Pharmacologic Treatments in Outpatient Settings, in February, which prioritized treatments based on economics and patient values.2 Here, ACP members balanced the benefits and harms of treatment from an economic standpoint. The updated guideline was informed by a comparative effectiveness systematic review that used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the effects of pharmacologic treatment to prevent episodic migraine.

This guideline stated there were no clinical advantages for newer, expensive medicine, and the recommended treatments for episode migraine headache in nonpregnant adults were monotherapy with a beta-adrenergic blocker (metoprolol or propranolol), antiseizure medication valproate, the serotonin and norepinephrine reuptake inhibitor venlafaxine, or the tricyclic antidepressant amitriptyline.

Patients who do not respond to or tolerate monotherapy are recommended a monotherapy with a calcitonin gene-related peptide (CGRP) antagonist (atogepant or Rimegepant) or a CGRP monoclonal antibody (eptinezumab, erenumab, fremanezumab, or galcanezumab. If patients still do not respond, the guidelines recommend monotherapy with the antiseizure medication topiramate.

Injectable CGRP-mAbs (eptinezumab, erenumab, fremanezumab, and galcanezumab) or oral CGRP antagonists-gepants (atogepant and rimegepant) had an annual cost from $7071 to $22,790. The analysis showed a low certainty that these drugs had intermediate value.

A little earlier in December, ACP published Incorporating Economic Evidence in Clinical Guidelines, which provided a framework for standardizing the approach to identifying, appraising, and considering economic evidence in the development of ACP clinical guidelines.3 The guidelines emphasized the importance of recognizing health care costs and the treatment’s impact on patients.

References

1. Qaseem A, Cooney TG, Etxeandia-Ikobaltzeta I, Wilt TJ, Harrod CS, Tice JA, Crandall CJ; Clinical Guidelines Committee of the American College of Physicians; Hicks LA, Cross JT Jr, Fitterman N, Lewis J, Linsky AM, Maroto M, Miller MC, Obley AJ, Owens DK, Shekelle PG, Shamliyan T, Yost J. Prevention of Episodic Migraine Headache Using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline From the American College of Physicians. Ann Intern Med. 2025 Feb 4. doi: 10.7326/ANNALS-24-01052. Epub ahead of print. PMID: 39899861.

2. Derman, C. New ACP Migraine Guidelines Show No Advantage for More Costly, Newer Medications. HCPLive. February 6, 2025. https://www.hcplive.com/view/new-acp-migraine-guidelines-show-no-advantage-pricy-newer-medications. Accessed March 17, 2025.

3. Qaseem A, Shamliyan T, Owens DK, Tice JA, Crandall CJ; Clinical Guidelines Committee of the American College of Physicians; Hicks LA, Wilt TJ, Balk EM, Cooney TG, Cross JT Jr, Fitterman N, Lewis J, Lin JS, Linsky A, Maroto M, Miller MC, Obley AJ, Shekelle P, Tufte JE, Etxeandia-Ikobaltzeta I, Harrod CS, Yost J, Qaseem A, Shamliyan T, Crandall CJ, Owens DK, Tice JA. Incorporating Economic Evidence in Clinical Guidelines: A Framework From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2025 Feb;178(2):241-248. doi: 10.7326/ANNALS-24-02149. Epub 2024 Dec 31. PMID: 39745810.