“Impressive” results for intranasal ketamine in migraine

Intranasal (IN) ketamine may be a viable treatment alternative for people with chronic, refractory migraine headaches that are unresponsive to other medications, new research shows.

Half of study participants who used IN ketamine for treatment-refractory chronic migraine in a new retrospective cohort study reported it as “very effective,” and over a third said it improved quality of life.



Dr. Hsiangkuo Yuan

“In our study, we showed that even with just a few uses per day, intranasal ketamine can still improve patients’ quality of life,” said lead researcher Hsiangkuo Yuan, MD, PhD. Medscape Medical News. Yuan is an associate professor of neurology at Thomas Jefferson University in Philadelphia and director of clinical research at the Jefferson Headache Center.

He added that “multiple drugs failed these patients and most patients had daily headaches. So if something works, even partially and for a short time, it could still give patients some relief to get them through the day.” .

The results were published online on May 30 Regional anesthesia and pain medicine.

Daily migraines, failed medications

The use of IN ketamine has not been studied for the treatment of treatment-refractory chronic migraine, although it has been studied in patients with cluster headaches and migraine, the researchers note.

Ketamine has not yet been approved by the US Food and Drug Administration for the treatment of migraines.

To further explore the effect of ketamine in those with treatment-refractory chronic migraine, the researchers retrospectively analyzed the electronic health records of Jefferson Headache Center patients who had received IN ketamine for migraine treatment between January 2019 and February 2020.

Of the 242 patients who had received IN ketamine, Yuan’s team followed up with 169 patients who agreed to be part of the study.

The majority (67%) experienced daily migraines, and 85% had tried more than three classes of migraine preventative medications. They have currently used a median of two drugs, the most common of which was a CGRP monoclonal antibody.

On average, patients used six puffs per day for a median of 10 days per month. The median onset of pain relief was 52 minutes after dosing.

Nearly three-quarters of patients reported at least one side effect of ketamine, most commonly fatigue (22%), double/blurred vision (21%) and confusion/dissociation (21%). These effects were mostly temporary, the researchers report.

The most common reasons for starting IN ketamine included an incomplete response to previous acute medications (59%), an incomplete response to previous preventive medications (31%), and prior benefit from IV ketamine (23%).

The study researchers noted that ketamine has the potential to be addictive and indicated that “physicians should consider using a potentially addictive drug such as ketamine only for significantly disabled patients with migraine.”

About half of the participants who used IN ketamine found it “very effective” and 40% found it “fairly effective.” Within the same group, 36% and 43% found the overall impact of IN ketamine on their quality of life was much better and slightly better, respectively.

Among those still using ketamine during study follow-up, 82% reported that ketamine was very effective.

Compared with other acute headache medications, IN ketamine was rated as much better (43%) or slightly better (30%).

Nearly 75% of participants reported using fewer pain relievers while using IN ketamine.

Yuan said future research could focus on finding predictors for response to IN ketamine or determining the optimal effective and safe dose for the drug in those with treatment-refractory chronic migraine.

“We still need a prospective, randomized controlled trial to evaluate the efficacy and tolerability of intranasal ketamine,” he added.

“Impressive result”



Dr Richard Lipton

Commenting on the results for Medscape Medical NewsRichard Lipton, MD, professor of neurology, psychiatry, and behavioral sciences and director of the Montefiore Headache Center at the Albert Einstein College of Medicine, New York City, said, “In this refractory population with multiple treatment failures, this is very impressive. open result.”

“These real-world data suggest that ketamine is an effective option for people with medically intractable chronic migraine headaches,” said Lipton, who was not part of the study. “In these very difficult-to-treat patients, 65 percent of those who started taking ketamine persisted. Of those who continued taking ketamine, 82 percent found it very effective.”

“This study makes me more confident that intranasal ketamine is a useful treatment option and I plan to use it more often in the future,” she added.

Like Yuan, Lipton emphasized the need for “well-designed placebo-controlled trials” and “rigorous comparative efficacy studies.”

The study was funded by Miles for Migraine. Yuan has received institutional support to serve as an investigator from Teva and AbbVie, and royalties from Cambridge University Press and MedLink. Lipton has received consulting fees from Alder/Lumbeck, Axsome, Supernus, Theranica, Upsher-Smith, and Satsuma. She has participated in speaking engagements for Eli Lilly and Amgen/Novartis and received institutional support to serve as principal investigator from Teva, GammaCore and Allergan/AbbVie. You have received paternity or royalty payments from Demos Medical, Cambridge University Press and MedLink.

Reg Anesth Pain Med. Published online May 30, 2023. Abstract

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