Patients with treatment-resistant major depression saw dramatic improvement after treatment with ketamine, according to results from a clinical trial.
According to researchers from the Icahn School of Medicine at Mount Sinai Hospital in New York City, the antidepressant benefits of ketamine, normally used as an anesthetic, were seen within 24 hours. Traditional antidepressants can take days or even weeks to demonstrate a reduction in depression, researchers noted.
Led by psychiatrists Drs. Dan Iosifescu, of Mount Sinai, Sanjay Mathew of Houston’s Baylor College of Medicine; and James Murrough, at Mount Sinai, the research team evaluated 72 people with treatment-resistant depression, which means their depression failed to respond to two or more medications.
These patients 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.
According to the researchers, 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, however, did not last for most, with only 45.7 percent reporting benefits seven days after treatment. Only 18 percent of people in the placebo group reported such benefit after a week.
“Using midazolam as an active placebo allowed us to independently assess the antidepressant benefit of ketamine, excluding any anesthetic effects,” said Murrough, who is first author on the new study. “Ketamine continues to show significant promise as a new treatment option for patients with severe and refractory forms of depression.”
Major depression is caused by a breakdown in communication between nerve cells in the brain, a process involving chemicals called neurotransmitters, the researchers explained. Traditional antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), influence the activity of the neurotransmitters serotonin and noreprenephrine to reduce depression, though the exact mechanism is not known.
But these medications can take a long time to make a difference — 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, the researchers said. It also works much more quickly than traditional antidepressants.
Further studies are needed to investigate the longer term safety and efficacy of ketamine in depression, according to Murrough.
He 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.
Because ketamine is a short-acting drug, it must be injected multiple times a week in order for a person to continue to receive its antidepressant effects. Longitudinal studies on its long-term use over the course of months or even years have not yet been done, so its long-term effects on a person’s health remain unknown.
“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,” he said. “Larger placebo-controlled studies will be required to more fully determine the safety and efficacy profile of ketamine in depression.”
“Major depression is one of the most prevalent and costly illnesses in the world, and yet currently available treatments fall far short of alleviating this burden,” said Dr. Dennis Charney, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai. Charney was among the researchers who discovered the potential of ketamine for treating depression.
“There is an urgent need for new, fast-acting therapies, and ketamine shows important potential in filling that void,” he said.