Club-drug ketamine relieves depression in largest patient study

(Bloomberg) -- The hallucinogen ketamine relieved symptoms of hard-to-treat depression within a day of treatment, in the largest study yet of the popular club drug’s use in psychiatry.

In the trial of 72 people whose depression hadn’t responded to at least two antidepressants, patients taking ketamine were twice as likely to report improvement than those on a placebo. The study, by researchers at the Baylor College of Medicine in Houston and Mount Sinai School of Medicine in New York, assessed patients after one day and again a week later.

The results support continued research into the use of ketamine, also known as Special K and used to anesthetize horses, for relieving low mood and feelings of hopelessness that plague as many as 350 million people globally. Researchers presented findings at the meeting of the American Psychiatric Association in San Francisco.

“Ketamine continues to show significant promise as a new treatment option,” says James W. Murrough, an assistant professor of psychiatry at Mount Sinai and one of the researchers involved in the study. Even so, “we have a long way to go before I think we can recommend it as treatment.”

Murrough’s research suggests ketamine may help depressed patients requiring urgent relief. The antidepressant benefits of ketamine were seen within 24 hours in the study, whereas traditional antidepressants can take days or weeks to alleviate symptoms.

More data are needed from depressed patients to establish the long-term effectiveness and safety of ketamine — a drug that’s toxic at high doses and known to cause psychotic-like symptoms, he said.

“The enthusiasm is a little bit ahead of the science,” Murrough says.

The medicine, whose street name is a play on Kellogg Co.’s Special K breakfast cereal, initially disinhibits brain circuitry, causing over-excitement in response to a stimulus.

Major depression is caused by a breakdown in communication between nerve cells in the brain, a process that is controlled by chemicals called neurotransmitters.

Ketamine influences brain receptors activated by a transmitter called glutamate to help restore the dysfunctional communication between nerve cells in the depressed brain, and much more quickly than traditional antidepressants.

Participants enrolled in Murrough’s study, which was sponsored by the National Institutes of Health, had suffered bouts of major depression over decades and a third had made suicide attempts, he says.

They were randomly selected to receive a single, intravenous dose of either ketamine or an active placebo of midazolam, another type of anesthetic without antidepressant properties. The treatments, given over 40 minutes, were sufficient to cause mild sedation and intoxication, he said.

After 24 hours, 63.8% of patients in the ketamine group reported a response, compared with 28% in the placebo group. After seven days, 45.7% still reported a response to ketamine, versus 18.2% in the placebo group.

 “Using midazolam as an active placebo allowed us to independently assess the antidepressant benefit of ketamine, excluding any anesthetic effects,” Murrough says.

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