Ketamine shows promise for hard-to-treat depression in new study

This week's research presents the strongest evidence to date that ketamine is at least as effective as electroconvulsive therapy for patients with depression resistant to treatment who do not have psychosis.

A new study suggests that, for some patients, the anesthetic ketamine is a promising alternative to electroconvulsive therapy, or ECT , currently one of the fastest and most effective therapies for patients with difficult-to-treat depression. The study is the largest direct comparison of the two treatments.

Patients who fail to respond to at least two antidepressants — about one-third of clinically depressed patients — have a disease that clinicians call "drug-resistant." Their options for relief are limited. Doctors typically recommend up to 12 sessions of ECT, which has long-established efficacy but is marred by the stigma of historical misuse and chilling Hollywood images of people tied to tables, writhing pain. Today's ECT is much safer and performed under general anesthesia, but the procedure remains underutilized.

The study, published Wednesday in the New England Journal of Medicine, found that ketamine, when given intravenously, was at least as effective as ECT in patients with treatment-resistant depression who did not have psychosis. (For people with psychosis, even very low doses of ketamine can make psychotic-like symptoms worse.)

"The results were very surprising to us “, said Dr. Amit Anand, lead author of the study and professor of psychiatry at Harvard Medical School who studies mood disorders at Mass General Brigham. His team initially speculated that ketamine would be nearly as effective as ECT. Instead, Dr. Anand said, they found ketamine worked even better than that.

This is important in part because some patients have trouble comfortable with the potential side effects of ECT, such as temporary memory loss, muscle pain or weakness. (In rare cases, this can lead to permanent memory lapses.)

The study, which was sponsored by the Cleveland Clinic Foundation, shows that ketamine is easier to administer, with fewer adjustments during treatment and fewer patients dropping out, Dr. Anand said. "More importantly, it shows that ECT, as expected, is associated with memory problems, whereas ketamine is not." Intravenous ketamine also has side effects, such as dissociation, but it's "usually not an unpleasant experience for patients," Dr. Anand said.

Previous studies have shown that both treatments can be effective in patients with difficult-to-treat depression, but this research has primarily looked at the two therapies independently. Dr. Roger S. McIntyre, a professor of psychiatry and pharmacology at the University of Toronto who is not affiliated with the study, called it "groundbreaking".

"It's that kind of pragmatic, rigorous, randomized and realistic, robust and very clinically meaningful data," said Dr. McIntyre.

The researchers randomly assigned intravenous ketamine or ECT to 365 patients. Almost half received ketamine twice a week while the others received electric shock therapy three times a week. At the end of the three-week treatment, 55% of people in the ketamine group and 41% of patients...