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ORLANDO, Fla. — Use of the recently approved non-opioid pain medication suzetrigine was associated with a decrease headache pain with tolerable side effects, a new study showed.

In the single-center retrospective cohort study, two thirds (67.5%) of the participants experienced improvement in their headache symptoms, whereas only 6.3% experienced worsening symptoms.

Though the study was small, was conducted mostly in patients with refractory headache, and lacked a placebo comparison, the results suggest value in studying suzetrigine as a potential treatment for headache disorders, lead investigator Molly Fensterwald, MD, assistant professor of neurology at the University of California, Los Angeles (UCLA), said.

“We do feel our findings support investigation of suzetrigine use in headache disorders, and that selective sodium channel inhibition is an exciting approach to treating headache, and hopefully we’ll see more new developments of pain therapies in this realm to come,” Fensterwald said.

The findings were presented on June 6 at the American Headache Society (AHS) Annual Meeting 2026 and published online simultaneously in Headache.

Acute Pain Drug for Headache?

Suzetrigine is a first-in-class non-opioid analgesic that the FDA approved last year for moderate-to-severe acute pain in adults on the basis of two phase 3 randomized controlled trials that showed efficacy comparable to hydrocodone and acetaminophen.

The drug is a selective sodium channel inhibitor, and there is some evidence to suggest sodium channel involvement in headache disorders, Fensterwald explained. For example, prior small studies of intravenous lidocaine, a sodium channel blocker, have shown efficacy in refractory headache, researchers reported.

“The issues with the current available treatments that have these properties is that they can lead to unwanted central nervous system side effects like sedation, ataxia, or vision changes,” as well as effects on other vital organs, she said.

To learn more about suzetrigine in headache, researchers conducted a retrospective descriptive analysis of patients seen at the UCLA Goldberg Migraine Program who were treated with suzetrigine for headache and facial pain disorders between January 2025 and February 2026. Of 1394 patients prescribed suzetrigine at UCLA Medical Center, 80 were part of the migraine program and had a documented response to the drug.

The patients were predominantly female (74%) with an average age of 48 years, and half (50%) were White.

Most were prescribed suzetrigine for a migraine disorder, followed by trigeminal autonomic cephalalgia, neuralgia and facial pain, secondary headache, medication-overuse headache, and other primary headache disorders.

Most patients had tried other rescue medications before, including nonsteroidal anti-inflammatory drugs, anti-calcitonin gene-related peptide (CGRP) agents, steroids, triptans/dihydroergotamine, and anti-emetics. One third had tried opioids, barbiturates, or ketamine.

Most had also used a wide range of preventive medications, including anti-CGRPs and anti-seizure medicines. Other preventive treatments used to a lesser extent include anti-hypertension drugs, memantine, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, chemodenervation, and nutraceuticals.

The primary outcome of patient response was assessed through the Patient Global Impression of Change, which asks “Since starting suzetrigine, how is your pain?” The scale runs from 0 (very much better) to 6 (very much worse). The researchers categorized the responses as “improved” for responses 0-2, “no change” for response 3, and “worsened” for responses 4-6.

Decrease in Pain Reported

Overall, 67.5% of patients reported improvement, including 13.8% who classified their pain as “very much better,” 25% “much better,” and 28.7% “minimally better.”

About a quarter of patients reported no change and 6.3% reported their symptoms worsened, including 3.8% who said they became “very much worse.”

The highest rates of improvement (83.3%) were in patients with trigeminal autonomic cephalalgias, whereas those with medication-overuse headache reported the least improvement.

Side effects were reported by 19% of patients, most commonly itching, muscle spasms, lightheadedness, and constipation.

“Our results indicate that suzetrigine shows potential benefit for patients with a variety of headache disorders who demonstrate inadequate efficacy or poor tolerability to currently available standard therapies,” researchers wrote.

Fensterwald acknowledged that the results were limited by the study’s retrospective, single-center design, and the lack of a placebo comparison. The dosing schedules of the patients also varied. Clinical trials are currently underway for longer term safety data, she said.

In response to an attendee question about paying for the medication, Fensterwald said that the easiest way for patients to pay for the drug currently is through the pharmaceutical company, Vertex Pharmaceuticals, which has a copay program, though that program may be ending toward the end of this year, she added.

“There’s a select number of insurance [plans] that do cover it, but I haven’t encountered that as much, and if there are issues, I usually send them to the copay program,” Fensterwald said.

Standard dosing is 100 mg as a loading dose, followed by 50 mg twice a day over 14 days, used as an acute medication.

Experts See Potential

Naveen George, DO, of University Hospitals Cleveland Medical Center in Cleveland, told Medscape Medical News that he’s had a few patients try suzetrigine, but the challenge is getting insurance to cover it long-term since its use for headache disorders is off label.

Despite that challenge, he sees the drug as very promising.

“It’s always great to have new options, and it’s a target that we can’t specifically address with available drugs,” George said.

Michael Yang, MD, a neurologist with Emplify Health System in La Crosse, Wisconsin, said he likes the fact that it is an agent that works outside the blood-brain barrier yet provides efficacy that is not seen with currently available therapies.

The study was funded by the Wendy and Leonard Goldberg Endowment. Fensterwald reported having no disclosures. Disclosures for other authors are available in the original article. George reported consulting for Pfizer, being a speaker for AbbVie and Lundbeck, and involvement in a clinical trial with Verve Therapeutics. Yang had no disclosures.