Experts say the spray approved this week by the FDA is the first truly new treatment for depression in decades.
No one believed the initial findings.
Dr. Dennis Charney and a colleague, Dr. John Krystal, had been studying antidepressants at Yale in the 1990s. Most of them targeted neurotransmitters in the brain — serotonin, norepinephrine, dopamine.
“We ultimately felt that couldn’t be the final answer because those drugs take weeks or months to work and don’t work in a lot of people,” Charney, now dean of the Icahn School of Medicine at Mount Sinai in New York, told Healthline.
The researchers eventually decided a different part of the brain, ionotropic glutamate receptors, might be involved, too.
The party drug ketamine, it turns out, can affect those receptors.
The researchers looked into whether the drug could be used to treat depression and found it started working within a few hours.
Charney says that even he was surprised by the results.
This week, that initial work on ketamine resulted in another milestone.
The approval by the Food and Drug Administration (FDA) of a form of esketamine as a nasal spray for patients with treatment-resistant depression marks the first truly new treatment for depression in decades, experts say.
Innovation in antidepressants had slowed in recent decades, so this week’s approval is being welcomed as a potential game-changer for the large number of people with depression for whom current treatments haven’t helped.
“There are upwards of 16 million people with depression, up to a third of whom have treatment-resistant forms,” Paul Gionfriddo, president of Mental Health America, told Healthline. “While there are good drugs on the market for depression, this has the potential to help a significant number of people for whom there has been no effective pharmaceutical treatment so far.”
“Esketamine offers hope to those patients,” Charney said, noting that studies found the new drug produced a response in about 70 percent of treatment-resistant patients studied.
The approval follows results Charney and colleagues published in 2006 showing that ketamine worked for those with treatment-resistant depression — depression that hasn’t responded to two or more different treatments — as well as more common depression.
They patented their treatment and licensed it to Janssen Pharmaceuticals, which is marketing the esketamine nasal spray under the brand name Spravato.
The treatment will be available only for adults who have treatment-resistant depression and only in conjunction with an oral antidepressant.
The spray will have to be administered in a doctor’s office or clinic, and patients will have to remain there for two hours for observation in case there are adverse reactions such as sedation or elevated blood pressure.
Initially, a new patient will receive the spray twice a week for a couple weeks and then with reduced frequency after that.
Charney said esketamine, a form of ketamine, is fast-acting, but its effects should last until the following dose.
Still, the eventual hope may be to reduce some of the inconvenience of these requirements.
“I’d like to see it roll out more widely and be made more accessible as soon as this is practical” assuming appropriate safeguards are put in place, said Gionfriddo.
“Right now, the FDA is concerned about side effects and so it wants to be sure that people who take this medication do so under supervision,” he said.
Over time, if side effects are limited, Gionfriddo hopes the observation period can limited or done away with, and eventually patients may even be able to administer the spray at home.
That could potentially get the drug to more people who might have had a hard time getting to clinics due to their depression.
However, some experts would prefer to see the drug administered in a professional setting.
Levine called esketamine the “first truly new medication for depression in about 60 years.” Those couple hours in a clinic, he said, can be a time for other supportive measures such as talk therapy or just checking in with the patient about their illness.
“Those are things you can’t do if someone is taking pills at home but can do in the office,” Levine told Healthline.
“It’s possible those restrictions could loosen over time, but it would lose something beyond just safety,” he said.
Charney predicted that thousands or maybe millions of patients are going to take the new drug. That’s a lot more than participated in clinical trials, of course, so researchers and regulators will be on the lookout for potential overlooked side effects or safety impacts.
For now, experts don’t see much risk of illicit or illegal use.
“I would have concerns if people were taking it home,” Levine said. But he said the restrictions “virtually eliminate the possibility of any negative outcomes.”
He estimates each nasal spray device will cost about $290 and that patients will go through two to three per treatment. Since it’s now FDA-approved he expects insurance to cover most of the cost.
The FDA has approved what is being hailed as the “first truly new” drug for depression in decades.
The esketamine nasal spray, using a form of the party drug ketamine, could give hope to the many people with depression for whom current antidepressants don’t work, experts say.
The development is being welcomed as a potential game-changer for the large number of people with treatment-resistant depression.