Anesthetic may help severe depression

NEW YORK – A single dose of the anesthetic ketamine appears to reduce depression in patients who show little improvement with standard medications, new research suggests.

The beneficial effects start less than 2 hours after the drug is given and last for about 7 days, according to results of a study conducted by investigators at the National Institutes of Health in Bethesda, Maryland.

A major problem with antidepressant medications is their late onset of effect, Dr. Carlos A. Zarate, Jr, and his colleagues note. Any option that would provide an antidepressant effect during this lag time would be of major benefit.

The researchers decided to look at ketamine as a treatment because it blocks an enzyme system that seems to play a key role in depression. Their study group included 17 patients with severe depression that failed to respond to at least two trials of antidepressants. They were required to have a score of at least 18 on a standard depression test called the Hamilton Depression Rating Scale (HDRS).

In the trial, the participants received an intravenous infusion of ketamine or inactive “placebo,” then switched to an infusion of the other agent 1 week later. To assess the onset and duration of effect, Zarate and his team used the HDRS at 60 minutes prior to the infusion, and at 40, 80, 110, and 230 minutes afterwards, then on days 1, 2, 3, and 7 days.

As reported in the Archives of General Psychiatry, patients treated with ketamine scored significantly lower on the HDRS at 110 minutes, lasting through 7 days, compared with those receiving placebo treatment. The HDRS at day 1 fell by up to 90 percent, indicating a substantial improvement in depression. Seventy-one percent of patients were classified as treatment responders and 29 percent had little or no evidence of depression on day 1 after the ketamine dose. The treatment response was maintained for at least 1 week by 35 percent of patients.

The authors note that the time that the antidepressant response began and lasted was “nearly identical” for each subject. They say, “The relatively prolonged antidepressant effect that occurred with ketamine is remarkable considering its short half-life, which is approximately 2 hours.”

None of the patients had any response to placebo.

“To our knowledge, there has never been a report of any other drug or (therapy) that results in such a dramatic, rapid and prolonged response with a single administration,” the investigators write.