Edward Fruitman, MD
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Ketamine’s Efficacy Validated in Major Refractory Depression

Caroline Cassels (Medscape.com)

Ketamine is a rapid, effective treatment for patients with treatment-resistant depression, new research shows.

The study showed that a single intravenous dose of ketamine, a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist, improved depression in 64% of patients within 24 hours of administration vs 28% of patients who received the anesthetic midazolam.

“Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression,” the investigators, with first author James Murrough, MD, assistant professor of psychiatry and neuroscience and associate director of the Mood and Anxiety Disorders Program at the Icahn School of Medicine at Mount Sinai, in New York City, write.

Reported in April 2013 at the Anxiety and Depression Association of America 33rd Annual Conference and covered by Medscape Medical News at that time, the results of 2-site, parallel-arm, randomized placebo-controlled study were published online August 28 in the American Journal of Psychiatry.

Promise of New Therapies

The study, which the researchers note is the largest to date to test the antidepressant effects of ketamine, included 73 participants with treatment-resistant major depression. Patients were randomly assigned in a 2:1 ratio to receive IV ketamine (n = 47) or midazolam (n = 25).

The study’s primary outcome was change in depression severity 24 hours after drug administration, as measured by the Montgomery-Ǻsberg Depression Rating Scale (MADRS).

Depression scores were not significantly different between treatment groups at 7 days.The researchers report that the likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% confidence interval, 1.21 – 4.14), with response rates of 64% and 28%, respectively.

Side effects associated with ketamine infusion included dissociative symptoms immediately following administration in 8 patients (17%). However, these side effects resolved by 2 hours postinfusion. In addition, for 2 patients, ketamine infusion was terminated due to significant changes in blood pressure.

The researchers note that more research is needed to identify strategies to prolong and maintain ketamine’s initial antidepressant response and to determine the drug’s long-term safety profile.

In an accompanying editorial, A. John Rush, MD, Duke–National University of Singapore Graduate Medical School in Singapore, writes that study does not validate a new treatment but rather points to a promising lead for new therapeutic development.

“While insufficient to recommend a wholesale change in practice presently, these results certainly provide substantial hope for patients with treatment-resistant depression, insight into the biology of this condition, and a major obligation by clinician scientists and funding agencies to answer this next set of important clinical questions for our patients with refractory depression,” Dr. Rush writes.


About the Author
Dr. Edward Fruitman graduated from the University of Michigan with a Bachelor of Science degree in Biology and Bachelor of Arts in Psychology. He went on to receive his Doctor of Medicine (MD) degree from Michigan State University, College of Human Medicine. Dr. Fruitman completed his residency at Einstein/Montefiore. He is a Diplomate of the American Board of Psychiatry and Neurology.

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