Ketamine Nasal Spray May Be Effective Migraine Treatment

By Pat Anson, PNN Editor

In recent years, ketamine has become a trendy drug for treating depression, anxiety, post-traumatic stress and some types of chronic pain. Usually administered by infusion or injection, ketamine is a non-opioid analgesic that acts on the brain by putting patients into a temporary dream-like state.

A new study at Thomas Jefferson University suggests that ketamine may also be an effective treatment for chronic migraine. Several previous trials have shown that intravenous ketamine is effective for chronic headache, but it required close monitoring by a pain specialist to adjust the dose and monitor any side effects.

In the new study, researchers gave 169 migraine patients a ketamine nasal spray that they could use at home without supervision. Over two-thirds of the participants suffered from daily headaches and nearly 85% had tried over 3 types of migraine prevention drugs, with limited success.

The study findings, published in the journal Regional Anesthesia & Pain Medicine, showed that nearly half the participants said the nasal spray was “very effective” and about 40% found it “somewhat effective.” Over a third said their quality of life was “much better.” 

Nearly 3 in 4 patients reported at least one side effect from ketamine, the most common being fatigue and double/blurred vision, followed by cognitive effects such as confusion, dissociation, vivid dreams and hallucinations. Most of the side effects were only temporary.

“In this descriptive study, intranasal ketamine served as an acute treatment for refractory chronic migraine by reducing headache intensity and improving quality of life with relatively tolerable adverse events. Most patients found intranasal ketamine effective and continued to use it despite these adverse events,” wrote lead author Michael Marmura, MD, Outpatient Director at the Jefferson Headache Center.

Marmura and his colleagues are cautious about who should use ketamine because of its potential for abuse. Ketamine has a short half-life of less than two hours, meaning patients may be tempted to use it repeatedly to keep chronic headaches at bay. Patients in this study used the nasal spray an average of just 6 times a month, but a small number (13.9%) used the spray daily.

“Clinicians should only consider the use of a potentially addictive medication such as ketamine for significantly disabled patients with migraine,” they warned. “(This) should be addressed carefully and individually, as some may respond only to repeated ketamine, while some may overuse it.”

In 2019, the FDA approved the use of Spravato, a nasal spray that contains a ketamine-like substance, for severe depression. Because of the risk of abuse, Spravato can only be administered in a doctor’s office, where patients can be observed for two hours after taking a dose. The use of such a spray to treat migraine would be considered an off-label use.

In addition to its medical uses, ketamine has long been known as a party drug – “Special K” -- because it can cause hallucinations and intense, dream-like states.

It didn’t take long for drug dealers to note the increase in ketamine’s popularity. Recent research published in JAMA shows that seizures of illicit ketamine in the U.S. have risen from 55 seizures in 2017 to 247 in 2022, a 350% increase. Because much of its was seized in powder form, researchers are concerned black market ketamine could easily be adulterated with illicit fentanyl.