A team of researchers funded by the National Institutes of Health (NIH) recently discovered why the drug ketamine may act as a rapid antidepressant.
Ketamine is best known as an illicit, psychedelic club drug. Often referred to as “Special K” or a “horse tranquilizer” by the media, it has been around since the 1960s and is a staple anesthetic in emergency rooms and burn centers. In the last 10 years, studies have shown that it can reverse — sometimes within hours or even minutes — the kind of severe, suicidal depression that traditional antidepressants can’t treat.
Researchers writing in the August 2010 issue of Archives of General Psychiatry reported that people in a small study who had treatment-resistant bipolar disorder experienced relief from depression symptoms in as little as 40 minutes after getting an intravenous dose of ketamine. Eighteen of these people had previously been unsuccessfully treated with at least one antidepressant medication and a mood stabilizer; the average number of medications they had tried unsuccessfully was seven. Within 40 minutes, 9 of 16 (56 percent) of the participants receiving ketamine had at least a 50 percent reduction in symptoms, and 2 of 16 (13 percent) had full remission and became symptom-free. The response lasted an average of about a week.
In a small 2006 NIMH study, one of the first to look at ketamine for depression, 18 treatment-resistant, depressed (unipolar) patients were randomly selected to receive either a single intravenous dose of ketamine or a placebo. Depression symptoms improved within one day in 71 percent of those who were given ketamine, and 29 percent of the patients became nearly symptom-free in a day. Thirty-five percent of patients who received ketamine still showed benefits seven days later.
In the most recent study published online in the journal Nature in May 2016, researchers discovered that a chemical byproduct, or metabolite, is created as the body breaks down ketamine. The metabolite reversed depression-like behaviors in mice without triggering any of the anesthetic, dissociative, or addictive side effects associated with ketamine.
“This discovery fundamentally changes our understanding of how this rapid antidepressant mechanism works, and holds promise for development of more robust and safer treatments,” said Carlos Zarate, MD, of the National Institute of Mental Health (NIMH), and a study coauthor and pioneer of research using ketamine to treat depression. “By using a team approach, researchers were able to reverse-engineer ketamine’s workings from the clinic to the lab to pinpoint what makes it so unique.”
In response to the Nature report, Sara Solovitch of The Washington Post wrote that “experts are calling [ketamine] the most significant advance in mental health in more than half a century.” She reported that many academic medical centers, including Yale University, the University of California in San Diego, the Mayo Clinic, and the Cleveland Clinic, have all begun offering ketamine treatments off-label for severe depression.
Therese Borchard, Associate Editor Psych Central. She is the founder of Project Hope & Beyond, an online community for persons with treatment-resistant depression and other chronic mood disorders. She blogs for Everyday Health and is the author of Beyond Blue: Surviving Depression & Anxiety and Making the Most of Bad Genes.