Preliminary results by Brain & Behavior Research Foundation NARSAD Young Investigator Grantee James W. Murrough, M.D.―in the largest clinical trial of ketamine for resistant depression to date―confirm the promise of the general anesthetic to quickly reduce symptoms of treatment-resistant depression for a majority of patients. This work on ketamine builds on studies led by Foundation-funded researchers since the 1990s.
According to Dr. Murrough, as many as 60% of patients with depression are not helped by currently-available antidepressant treatments and for those who are helped, it can take several weeks for the beneficial effects to be felt. The difference between ketamine and most antidepressants currently on the market is that it targets glutamate receptors instead of serotonin and noreprenephrine neurotransmitters.
Dr. Murrough and team studied 72 patients with treatment-resistant depression. To qualify for the study subjects had to have a history of unresponsiveness to at least three other biological treatments. Study participants were divided into two groups; one group received ketamine and the other received midazolam, another anesthetic that is not thought to have antidepressant effects.
Within one day or less, approximately 64% of participants who were given the intravenous dose of ketamine and 28% of the patients who were given the placebo experienced improvement of depression symptoms. The benefit of the treatment appeared to continue for at least a week in about 46% of the ketamine group and about 18% of the midazolam group, and major side effects were not reported. More research is needed to rule out whether ketamine has addictive qualities and to determine the frequency with which the treatment could be given to each patient.
"Using midazolam as an active placebo allowed us to independently assess the antidepressant benefit of ketamine, excluding any anesthetic effects," said study first author Dr. Murrough, assistant professor of psychiatry, Mood and Anxiety Disorders Program, Icahn School of Medicine at Mount Sinai, NY. "Ketamine continues to show significant promise as a new treatment option for patients with severe and refractory forms of depression…We found that ketamine was safe and well tolerated and that patients who demonstrated a rapid antidepressant effect after starting ketamine were able to maintain the response throughout the course of the study. Larger placebo-controlled studies will be required to more fully determine the safety and efficacy profile of ketamine in depression."
The results of the study have yet to be reviewed for publication but were reported by Dr. Murrough at the American Psychiatric Association 2013 Annual Meeting in San Francisco, CA, during the New Research Press Briefing on May 20, 2013. The press conference was hosted by Brain & Behavior Research Foundation President Jeffrey Borenstein, M.D.