For the first time in 30 years, the Food and Drug Administration has approved a new treatment for depression.
Last month, an FDA advisory committee recommended that federal regulators approve a nasal spray that delivers the active ingredient of ketamine to be used as a treatment for adults with severe depression. Ketamine was first introduced as an anesthetic in the 1960s but has also become a well-known recreational drug.
In 2013, the FDA designated the drug as a “breakthrough therapy,” which speeds up the review process for a treatment for serious or life-threatening conditions.
The drug, called Spravato (known chemically as esketamine – a cousin of ketamine), was developed by the Janssen Pharmaceutical Companies of Johnson & Johnson and is aimed at people with treatment-resistant depression, or those who have tried at least two other antidepressants without success.
“I believe there is compelling evidence that esketamine is an effective treatment for this highly treatment resistant population,” said advisory panel member Walter Dunn, MD, PhD, of the University of California, Los Angeles. “From our experience with ketamine off-label use for the last 10-plus years, we know it works and we know it works fast.”
About one-third of people with depression do not find relief with current treatments, according to Mark Rasenick, a professor of physiology, biophysics and psychiatry at the University of Illinois at Chicago. “These are people who have not found a remedy in more traditional drugs, they need and deserve our help,” he said. “It’s good that something will be available for people who might otherwise (commit) suicide.”
But Rasenick, who is working on developing personalized depression treatments, has some reservations about using ketamine for such treatment. “It is a club drug. ‘Special K’ is the popular version of it,” he said, adding it can cause dissociative effects in users.
There is also not a lot of data on long-term ketamine use, Rasenick said, other than data “from addicts who may have a variety of health problems in addition to whatever the ketamine is doing,” he said.
He’s also concerned about potential diversion. “When it gets out to the general public, even though it’s supposed to be tightly controlled, who knows what happens and it’s a lot easier to put something in your nose than in your veins.”
Dr. Danesh Alam calls the drug a breakthrough, particularly in treating suicidal thoughts. Alam is the medical director of Behavioral Health Services at Northwestern Medicine Central DuPage Hospital, where clinical trials involving esketamine are being conducted. “I feel that will be probably the next frontier for this drug – where you actually have medication to treat suicidal thoughts very quickly, which makes this a remarkable option.”
Spravato will be administered under the supervision of health care professionals rather than dispensed to patients for at-home use to mitigate potential misuse and abuse, as well as allow health care providers to monitor patients for side effects, like dissociation and sedation, according to the FDA. “The most common side effects are a brief episode of dissociation, out-of-body sensations,” Alam said. “Generally folks tolerate it pretty well. The concern is really around the abuse potential. The way the study was designed there is no ability to measure its abuse potential since they didn’t think it was a good idea to allow patients to take the inhalers home. I think the concern we have is the population that abuses ketamine develops serious problems – urinary and memory problems – so there’s reason to believe there could be brain damage with chronic use.”
The Spravato labeling contains a “boxed warning” informing patients they are at risk for sedation, difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug.
This is the first FDA approval of esketamine for any use.
Note: This story was first published March 4, 2019. It has been updated following our conversation with Dr. Danesh Alam.