Ketamine holds promise for people with treatment-resistant depression
Washington: In a new study, patients with treatment-resistant major depression saw dramatic improvement in their illness after treatment with ketamine, an anesthetic.
The largest ketamine clinical trial to-date was led by researchers from the Icahn School of Medicine at Mount Sinai.
The antidepressant benefits of ketamine were seen within 24 hours, whereas traditional antidepressants can take days or weeks to demonstrate a reduction in depression.
Led by Dan Iosifescu, MD, Associate Professor of Psychiatry at Mount Sinai; Sanjay Mathew, MD, Associate Professor of Psychiatry at Baylor College of Medicine; and James Murrough, MD Assistant Professor of Psychiatry at Mount Sinai, the research team evaluated 72 people with treatment-resistant depression-meaning their depression has failed to respond to two or more medications-who were administered a single intravenous infusion of ketamine for 40 minutes or an active placebo of midazolam, another type of anesthetic without antidepressant properties.
Patients were interviewed after 24 hours and again after seven days. After 24 hours, the response rate was 63.8 percent in the ketamine group compared to 28 percent in the placebo group. The response to ketamine was durable after seven days, with a 45.7 percent response in the ketamine group versus 18.2 percent in the placebo group. Both drugs were well tolerated.
"Ketamine continues to show significant promise as a new treatment option for patients with severe and refractory forms of depression," said Dr. Murrough, who is first author on the new report.
Major depression is caused by a breakdown in communication between nerve cells in the brain, a process that is controlled by chemicals called neurotransmitters. Traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs) influence the activity of the neurotransmitters serotonin and noreprenephrine to reduce depression.
In these medicines, response is often significantly delayed and up to 60 percent of people do not respond to treatment, according to the U.S Department of Health and Human Services. Ketamine works differently than traditional antidepressants in that it influences the activity of the glutamine neurotransmitter to help restore the dysfunctional communication between nerve cells in the depressed brain, and much more quickly than traditional antidepressants.
Future studies are needed to investigate the longer term safety and efficacy of a course of ketamine in refractory depression.
Dr. Murrough recently published a preliminary report in the journal Biological Psychiatry on the safety and efficacy of ketamine given three times weekly for two weeks in patients with treatment-resistant 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," Dr. Murrough said.
"Larger placebo-controlled studies will be required to more fully determine the safety and efficacy profile of ketamine in depression," he added.
The research will be discussed at the American Psychiatric Association meeting on Monday, May 20, 2013 at 12:30 pm in the Press Briefing Room at the Moscone Center in San Franscico.