FDA Approves Esketamine Nasal Spray For Hard-To-Treat Depression

Mar 5, 2019
Originally published on March 10, 2019 11:49 am

Editor's note, March 6, 9:30 a.m.: This story was updated to include information about the price of Spravato.

The Food and Drug Administration approved the first drug that can relieve depression in hours instead of weeks.

Esketamine, a chemical cousin of the anesthetic and party drug ketamine, represents the first truly new kind of depression drug since Prozac hit the market in 1988.

The FDA's decision came Tuesday, less than a month after a panel of experts advising the agency voted overwhelmingly in favor of approval.

"There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition," said Dr. Tiffany Farchione, acting director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research, in a press release about the decision.

"This is potentially a game changer for millions of people," said Dr. Dennis Charney, dean of the Icahn School of Medicine at Mount Sinai in New York. "It offers a lot of hope."

Esketamine works through a mechanism different from those of drugs like Prozac, Charney said. And that is probably why studies show it can often help people with major depressive disorder who haven't been helped by other drugs.

"Many of them are suicidal," Charney said. "So it's essentially a deadly disease when you haven't responded to available treatments and you've been suffering for years if not decades."

Charney was part of the team that first showed two decades ago that ketamine could treat depression. He also is named as co-inventor on patents filed by the Icahn School of Medicine relating to the treatment for treatment-resistant depression, suicidal ideation and other disorders.

Esketamine, developed by Johnson & Johnson, will be administered as a nasal spray and be used in conjunction with an oral antidepressant. It will be marketed under the brand name Spravato. The FDA has approved it for patients who have failed to respond adequately to at least two other drugs.

That means about 5 million of the 16 million people in the U.S. with major depression might benefit from esketamine, said Courtney Billington, president of Janssen Neuroscience, a unit of Johnson & Johnson.

But esketamine presents some challenges because of its similarities to ketamine. In high doses, both drugs can cause sedation and out-of-body experiences. And ketamine, often called Special K in its illicit form, has become a popular party drug.

So Johnson & Johnson is taking steps to make sure esketamine will be used only as intended, Billington said.

"Spravato will not be dispensed directly to a patient to take at home," he said. "It will only be available in approved and certified treatment centers."

Patients will inhale the drug under supervision at these centers once or twice a week. And they will receive a dose that is unlikely to produce side effects such as hallucinations.

"The amount of active ingredient that's in this product, it's at a very, very low dose," Billington said.

Even so, the FDA, according to its press release, is requiring a warning label that says patients "are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug,"

Esketamine's approval comes as more and more doctors have begun administering a generic version of ketamine for depression. Generic ketamine is approved as an anesthetic, not as an antidepressant. Even so, doctors can legally prescribe it for off-label medical uses.

And as a growing number of studies have shown ketamine's effectiveness against depression, ketamine clinics have sprung up around the United States. These clinics often administer the drug in an intravenous infusion that can cost more than $500 per treatment.

Many doctors who have become comfortable offering ketamine for depression probably won't switch to esketamine, said Dr. Demitri Papolos, director of research for the Juvenile Bipolar Research Foundation and a clinical associate professor at Albert Einstein College of Medicine.

For the past 10 years, Papolos has been prescribing an intranasal form of ketamine for children and adolescents who have a disorder that includes symptoms of depression.

"I'm very pleased that finally the FDA has approved a form of ketamine for treatment-resistant mood disorders," Papolos said. He said the approval legitimizes the approach he and other doctors have been taking.

But he hopes that doctors who are currently using ketamine continue to do so. "It'll be a lot less expensive and a lot easier for their patients [than esketamine]," he said.

And animal studies show it's possible that old-fashioned ketamine is a more potent antidepressant than esketamine, Papolos said.

Esketamine "may not be as effective as a generic that any psychiatrist or physician can prescribe without restrictions," Papolos said.

Johnson & Johnson said the wholesale cost of each treatment with esketamine will range from $590 to $885, depending on the dose. That means twice-weekly treatments during the first month will cost centers that offer the drug at least $4,720 to $6,785. Subsequent weekly treatments will cost about half as much.

The drugmaker says those figures don't include administration and observation costs.

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DAVID GREENE, HOST:

For the first time in decades, the FDA has approved a major new drug to treat depression. It's a nasal spray that can relieve symptoms in hours rather than weeks. This medicine is called Spravato. And it's produced by Johnson & Johnson. It's based on the anesthetic ketamine, which has a reputation as a club drug. Psychiatrists such as Martin Teicher of Harvard Medical School have been studying the use of this drug to treat a growing number of disorders.

MARTIN TEICHER: I think it's, actually, one of the biggest advances in psychiatry in a very long time. It doesn't work for everybody. But it's sort of remarkable to have a treatment that can work pretty much immediately.

GREENE: NPR science correspondent Jon Hamilton is with me in the studio.

Hi, Jon.

JON HAMILTON, BYLINE: Hi.

GREENE: All right - biggest advancements in psychiatry in a very long time. How is this anesthetic different than other antidepression drugs we've had out there?

HAMILTON: Well, I should say that scientists don't really know how any antidepressant works.

GREENE: Oh, interesting.

HAMILTON: (Laughter) But that said...

GREENE: But they work. I mean, they clearly have...

HAMILTON: They do work.

GREENE: They do work.

HAMILTON: They do work. But exactly what they're doing in the brain is still a mystery. And the thing they do know is that drugs like Prozac, the drug people probably know best, target the brain's serotonin system, whereas Spravato targets the brain's glutamate system. And it also, by doing this, may help the brain rewire itself, forming new connections.

GREENE: So the psychiatrist there said this is not - this drug won't work for everyone. Like - so who are the candidates who might use this nasal spray?

HAMILTON: This is a drug for people who have what is called treatment-resistant depression. And the way the FDA is defining that right now is that you have to have failed to respond adequately to at least two other treatments for depression. And a few months ago, I spoke to a patient who was - had depression and had not responded to any drug - he tried everything - until he was prescribed ketamine. This guy's name is James. He's an advertising executive. And he didn't want us to say his full name because he was afraid it would hurt his career.

JAMES: My wife took a summer off to be with me because she was scared of what was going to happen to me. She would go to work for a few hours, rush home. There'd be times I'd call her, just screaming, please come home. I can't get through another minute.

HAMILTON: So the amazing thing is that when James started on ketamine, he totally recovered. He was able to go back to his job. He said he felt calm. And there are a lot of people like James out there. There are about 5 million other people in the U.S. who have this sort of treatment-resistant depression. And for them, this could be a real lifeline, this new drug.

GREENE: So the FDA approving it is something that you can use if other treatments have not worked. Is that a sign that the FDA's being really cautious with this?

HAMILTON: Yeah. And there are good reasons to be cautious. We mentioned it's a club drug. And Spravato, like ketamine, which it's based on, it can produce some pretty major side effects. People talk about memory loss, a sense of being unable to control their bodies, hallucinations. I mean, it's a lot. And so patients won't be able to take Spravato at home. The whole idea is that they will have to go to a certified treatment center to take this. And then they will be observed not just when they take the drug but for a couple of hours after to make sure the side effects aren't a problem.

GREENE: But it can work really quickly, right? I mean, does that mean that this is something that people will use in a real crisis?

HAMILTON: It could be. But the effects of ketamine are almost instantaneous. People talk about feeling better within hours. However, the effects wear off with most patients after a few days or a week. And so people are going to have to go back and take additional treatments at first for - twice a week and maybe once a week after that.

GREENE: NPR science correspondent Jon Hamilton with us in the studio this morning. Jon, thanks as always.

HAMILTON: You're welcome.

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