A Ketamine-Like Drug to Treat Depression Could Soon Gain FDA Approval
Esketamine meets an "unmet medical need."
Until recently, the Food and Drug Administration’s newly greenlit treatment for depression might have seemed more at home in a club than in a mental health clinic. Esketamine, a chemical very closely related to the party drug ketamine, is the active ingredient in a new Johnson and Johnson nasal spray discussed by a panel of FDA experts on Tuesday. After reviewing the research, the panel voted overwhelmingly in favor of the drug’s safety and efficacy for treating depression, taking it one step closer toward FDA approval.
Ketamine is used medically as an anesthetic and, less legally, as a party drug because of its ability to induce a trance state. In spite of this reputation, both ketamine and its cousin esketamine have shown promise as a treatment for depression and migraines.
In the meeting on Tuesday, the FDA advisory was swayed by that existing evidence, and voted 14-2 in favor of the drug, reports NBC News.
“I think esketamine has the potential to be a game-changer in the treatment of depression … I use the term potential because the issues of cost and patient accessibility need to be addressed,” said Walter Dunn, Ph.D., one of the panel members.
The Potential Downsides
Deciding whether esketamine should get the FDA’s stamp of approval meant balancing its potential for abuse with its potential for treatment. Right now, ketamine is a Schedule III drug in the US, suggesting that it has a moderate to low potential for abuse (Tylenol with codeine is also in this category). But that’s not to say that it doesn’t come with risks: For example, some research shows that it affects opioid receptors— the same ones implicated in opioid abuse and addiction — suggesting that there needs to be a plan to help prospective patients wean themselves off esketamine eventually. In briefing documents, the FDA’s panel also advised including a warning statement on the drug alerting users that “the long-term cognitive effects of repeated exposure to ketamine are not well understood.”
"“It’s been around for 50 years. Those of us who have seen it used know the adverse-event profile is large."
The panel, unsurprisingly, is being extremely cautious about the new drug. One member, Steve Meisel, Ph.D., system director of medication safety at Fairview Health Services in Minneapolis, went so far as to call it a “nasty drug.”
“It’s been around for 50 years. Those of us who have seen it used know the adverse-event profile is large,” he told Bloomberg.
The Potential Upsides
Nevertheless, there is compelling evidence that esketamine both fills a gap in mental health treatment and may actually provide better treatment than current options for depression. For example, a paper published in 2018 in the American Journal of Psychiatry showed that an esketamine nasal spray was more effective than a placebo in treating major depressive disorder and alleviating thoughts of suicide in six patients. That’s just one example of numerous clinical trials in the US and beyond showing similar results.
In addition to weighing the science behind esketamine, the panel also considered how it compares to existing treatments for depression. In documentation outlining the FDA’s approach to reviewing the drug, the agency specifies that the drug is meant to address treatment-resistant depression (TRD) — that is, depression that hasn’t responded to at least two other types of treatment. The current options for treating this type of depression are limited, and even the FDA admits they’re not great: “TRD treatments remain an unmet medical need,” state the documents from Tuesday’s meeting.
What’s Next for Esketamine?
In short, the idea that ketamine could become a good treatment option for certain types of depression has been circulating for awhile. The results of Tuesday’s vote could go a long way in securing FDA approval for the drug.
Still, it’s far from a done deal. Although the 14-2 vote seems like a good indicator that the nasal spray might see FDA approval, the agency won’t officially announce its decision until March 4th.