New ACP guidelines advise combination therapy for treatment of acute episodic migraines

Key takeaways:

• ACP’s guidance on treating acute episodic migraines centers around combination therapy through a triptan.
• ACP also recommends prescribing less costly medications and suggesting lifestyle changes to patients.

ACP released new clinical guidance on outpatient treatment of acute episodic migraine with combination therapy in patients who are not pregnant or lactating in outpatient settings.

The two recommendations come after the association recently issued guidelines on the prevention of such migraines, which are defined as one to 14 headache days a month.

Amir Qaseem, MD, PhD, MHA, MGIN, MRCP, FACP, ACP chief science officer and senior vice president of clinical policy at the Centers for Evidence Reviews, and colleagues wrote in Annals of Internal Medicine that migraines account for 4 million ED visits and 4.3 million office visits in the U.S. yearly, “representing an important health problem and a substantial economic burden of more than $78 billion annually in medical expenses and lost productivity.”

A migraine, or a recurrent moderate or severe headache lasting 4 to 72 hours with or without sensory disturbances, “is very common, especially in women, yet remains underdiagnosed and undertreated,” Qaseem told Healio.

ACP used the Grading of Recommendations, Assessment, Development and Evaluation approach, systematic reviews and a meta-analysis to assess several clinical outcomes of pharmacologic treatments for acute episode migraine, including:

• pain relief and pain freedom at 2 hours;
• sustained pain relief and sustained pain freedom up to 48 hours;
• nausea, vomiting and restored physical function at 2 hours;
• the need for rescue medication within 24 hours; and
• overall and serious adverse events.

The guidelines committee identified further data on adverse events through FDA medication labels.

Recommendations

ACP’s first recommendation said physicians should add a triptan to an NSAID prescribed to treat moderate to severe episodic migraine in nonpregnant patients in outpatient settings who have not adequately responded to the drug.

Qaseem and colleagues noted that the evidence behind this “strong” recommendation — the classification of which means there is confidence that the benefits clearly outweigh the risks — is of moderate certainty.

In the second recommendation, ACP suggests adding a triptan to acetaminophen given to nonpregnant patients suffering from moderate or severe episodic migraine who have not adequately responded to the treatment.

This recommendation’s evidence is of low certainty. It is also classified as being conditional, meaning the benefits probably outweigh the risks but that there is “appreciable uncertainty.”

Lifestyle changes also suggested

The researchers highlighted several considerations and implications stemming from the guidance, such as that patients who may not respond well to one recommended migraine treatment “may respond to another within the same drug class.”

Qaseem and colleagues, who recommended to prescribe less costly medications, also pointed out that physicians should suggest lifestyle changes that could help treat episodic migraines to patients.

Such modifications may include maintaining regular meals, staying hydrated, consistently exercising, managing stress through relaxation and meditation techniques, and pursuing weight loss in cases where the patient has overweight or obesity.

“Also, explore modifiable migraine triggers or contributing factors during a detailed history,” they wrote.

Editorial

The guidance shows that ACP “recognizes that acute treatment may involve a step care approach,” Marianna Shnayderman Yugrakh, MD, an assistant professor of neurology at Columbia University Medical Center, wrote in an accompanying editorial.

Health care providers “need to think beyond guidelines to optimize the treatments for individual patients with each subsequent encounter” as literature on the effectiveness of newer migraine treatments grows, she noted.

“An individual’s migraine symptoms may warrant specific drugs from a class, and patients whose symptoms vary by attacks may need several different treatments,” Yugrakh added. “Although patients may generally prioritize effectiveness over potential harms, preferences should always be assessed individually.”

For more information:

Amir Qaseem, MD, PhD, MHA, MGIN, MRCP, FACP, can be reached at aqaseem@acponline.org.

References:

• Qaseem A, et al. Ann Intern Med. 2025;doi:10.7326/ANNALS-24-03095.
• Yugrakh M. Ann Intern Med. 2025;doi:10.7326/ANNALS-25-00372.