Ketamine shows antidepressant effect in refractory depression

FDA Highlights by Bruce Sylvester – Researchers report that, in a double-blind trial involving clinically depressed patients who had not responded to at least three prior antidepressants, intravenous ketamine therapy improved symptoms of depression within 24 hours.

The findings were published online on August 28, 2013 by The American Journal of Psychiatry (AJP).

Lead investigator Sanjay Mathew, M.D., associate professor at Baylor College of Medicine in Houston, Texas, said that that the findings are particularly helpful, “because the currently available antidepressants don’t offer patients with treatment-resistant major depression a very good prognosis. Ketamine is also important because it works on a neurotransmitter system different from the ones affected by current antidepressants.”

The investigators enrolled 72 subjects, the largest group studied to-date in a trial of ketamine for depression. They measured improvement at 24 hours after initial ketamine dosing. Midazolam, with similar sedative side effects to ketamine, was chosen as a comparator.

They reported that 64% of the ketamine-treated subjects achieved improvement in symptoms of depression at 24 hours after a single dosing, compared to 28% of midazolam-treated subjects.

All subjects had been screened to exclude those with a history of a psychotic illness or bipolar disorder, alcohol or substance abuse in the previous 2 years, unstable medical illnesses, serious and imminent suicidal or homicidal risk and other medical issues.

Eight ketamine-treated subjects (17%) showed some dissociative symptoms immediately after the initial dosing. These side-effects ended within 2 hours post-infusion.

The investigators reported no severe psychotic side-effects.  Two patients had their ketamine infusion terminated because of significant changes in blood pressure.

The authors noted that the trial suggests a role of the N-methyl-D-aspartate glutamate receptor in depression, a receptor not currently activated by existing antidepressant drugs.

In an accompanying editorial, A. John Rush, M.D., professor of psychiatry at the University of Texas Southwestern Medical Center in Dallas, Texas, said that, while the findings point toward a promising lead for a new therapeutic development, they do not validate a new treatment.