Why the New Ketamine-Like Drug for Depression is a Big Deal
If you haven’t found an antidepressant that works for you, there might be hope for the first time in 30 years: The FDA just approved a new ketamine-based drug to help treatment-resistant depression.
The new medication—a nasal spray based on ketamine’s chemical sibling, esketamine—has two serious selling points: For starters, it can help the 30 to 40 percent of people with major depressive disorder who have had no luck with other antidepressants.
How it works
With other antidepressants on the market, “the difference from one kind to another is kind of like Coke to Pepsi,” says Men’s Health advisor Drew Ramsey, M.D., assistant clinical professor of psychiatry at Columbia University. “But ketamine is like kombucha.” While the majority of antidepressants work by influencing serotonin and epinephrine through your monoamine system, ketamine instead binds to entirely separate GABA receptors, forming new neural connections and actually stimulating brain growth.
The other reason esketamine is remarkable: While you have to wait anywhere from four weeks to three months to see if something like Zoloft will help depression (and then, if it doesn’t, you have to start the trial all over again with a new med), ketamine can improve your mood within a few hours, up to a few days.
The news that ketamine helps depression isn’t new. People have been using the drug off label for the mood disorder for the better part of a decade, and there are ketamine clinics all over the country where depressed patients can get the drug intravenously. The new medication is basically the same thing but in a nasal spray, which means it doesn’t involve needles and is therefore less scary and less costly.
Esketamine, to be marketed under the name Spravato, will have to be administered by a psychiatrist (more on why that’s super important in a minute), and the effects of one dose last about two to four weeks. It doesn’t work for everyone—Ramsey says it helps anywhere between 40 to 70 percent of people—but you’ll know if it does for you after just one infusion, which significantly speeds up the search for effective treatment, he adds. If it is effective, you’re looking at an infusion once or twice a month, instead of taking a pill every day.
Most people don’t question esketamine’s safety for the right population. Despite its reputation as a club drug, ketamine has been used in hospitals as an anesthetic for decades and the dose in the nasal spray is significantly lower than what people abuse.
But the science behind the drug’s efficacy is a bit controversial—mostly because two of five key studies didn’t meet their primary endpoints.
There is a whole subgroup of people with treatment-resistant depression who this drug isn’t right for—namely those with psychotic symptoms, for whom the ketamine can worsen episodes, and those with a history of substance or alcohol abuse.
Officially, the FDA lists sedation and blood pressure spikes as major risks. But the biggest risk, Ramsey says, is that you essentially have a bad mini trip. In order for esketamine to work, you have to experience dissociation, or the feeling of disconnecting from your thoughts, feelings, or sense of identity. Whether this is a pleasant, neutral, or unpleasant experience totally depends on the person, Ramsey explains. It can take people anywhere from a few hours to a few days to recover from a negative infusion experience, but the effects aren’t long term, he assures.
Thomas Kosten, M.D., professor of psychiatry and pharmacology at Baylor College of Medicine, foresees potential issues when the drug leaves clinical trials and enters the real world. “Most people don’t have clean depression—many have a dual diagnosis with other symptoms and disorders, so if you have a bad diagnosis, ketamine could make psychotic symptoms worse,” he explains. And there’s concern over the initial mood boost reducing the chances of getting long-term help if you receive esketamine in, say, the ER after being admitted for a suicide attempt.
Ramsey doesn’t refute that there are risks. “You’re giving a powerfully psychoactive medication to a patient with a severe psychiatric concern. Are there risk things will go wrong? Of course. But that’s why you put yourself in the hands of trained staff,” he says.
For the most part, the fact that the drug has to be prescribed and administered by a clinician will definitely help direct it to appropriate candidates, minimize abuse, and make unpleasant dissociations less scary. And, regardless of these side effects, the reality is: For many who suffer severe depression and haven’t found any lasting relief with the antidepressants available, esketamine offers a promise at recovery they don’t otherwise have.
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