After trying antidepressants, psychotherapy and other treatments like electroconvulsive therapy, people with tough-to-treat depression are often out of options.
In recent years, however, there’s been fresh hope in an unexpected place: the club drug ketamine. Ketamine hydrochloride has been found in some small studies to help treatment-resistant depression. Research like this—and the buzzy headlines that follow it—have stoked curiosity in both clinicians and patients, leading to the rise of costly ketamine clinics, where a single dose can cost $500, and the off-label use of the drug for mood disorders. (Ketamine is FDA-approved as an anesthetic.)
Still, ketamine isn’t quite ready to be considered a primetime treatment for depression, concludes an American Psychiatric Association (APA) research task force in a new report published in JAMA Psychiatry.
“The evidence that we have to date clearly suggests there’s a very strong rapid antidepressant effect, but we don’t have great data on the longer-term efficacy and safety,” says lead author Dr. Gerard Sanacora, professor of psychiatry and director of the Yale Depression Research Program and a longtime researcher of ketamine’s effects on depression.
In studies, when depressed people who have exhausted their options take ketamine, 50-75% of them (and sometimes even more) feel at least 50% better within a day, Sanacora says. “For most antidepressants, it takes at least six weeks to get to that point,” he says. “I’ve had many patients who were acutely suicidal, have taken this medicine and report within 24 hours that they’re no longer suicidal. We see these amazing turnarounds, and we see them not uncommonly.”
But researchers, even the optimistic ones, still have a lot of questions about the drug. First of all, they aren't sure why it works—what the mechanism is. The positive effects seem to last for a few days or a week, but it’s not yet known what happens when people continue to take it for a few months or a year, nor is it known what happens when people stop taking it altogether. Experts also do not know the best dose for treating depression.
One of the problems is that a small number of people with depression—only about 368—have taken the drug in clinical trials. “That’s pitifully small compared to what a clinical trial would generally be comprised of for FDA approval,” says Dr. Charles Nemeroff, chair of the APA task force and chairman of the department of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine.
Ketamine is not a risk-free drug, and some patients have developed an increase in blood pressure in ketamine trials—part of the reason why the authors strongly advise against taking ketamine unsupervised or in a clinic that’s not equipped to handle complications like unexpected changes in heart functioning, respiration or dangerous behavior. Chronic use of ketamine has been linked to cognitive impairment and bladder inflammation.
Another concern is that ketamine, sometimes called “special K,” is a drug of abuse. “The last thing we would want to do as a field would be to promote the use of a substance to treat depression that turns out to have tremendous abuse liability, and that would end up creating a cadre of depressed patients who are now, in addition to that, substance abusers,” Nemeroff says.
While ketamine shows early promise for a condition with few other options, the authors urge further research to address these gaps in knowledge about the drug. “I still think it quite possibly is the most exciting finding in the field of depression research for the past 50 years,” says Sanacora. “It’s one of the most difficult things to face as a physician: that balance between not offering a treatment that has potential life-changing ability for some patients, but balancing that against the limited amount of data that we have on it.”