FDA approves Johnson & Johnson’s nasal spray for depression as standalone treatment

The Food and Drug Administration on Tuesday approved Johnson & Johnson‘s nasal spray to be used alone in adults with a major depressive disorder that is difficult to treat, as sales of the drug grow. 

The spray, called Spravato, is now the first-ever standalone therapy for treatment-resistant depression, which is when trying at least two standard treatments does little to nothing to improve depression symptoms in a patient. 

Previously, Spravato was cleared in the U.S. to use together with an oral antidepressant for both treatment-resistant depression and for people with major depressive disorder who are experiencing thoughts of suicide or harm. The drug first entered the U.S. market in 2019. 

“We want to recognize that this is a medicine that treats a disease that [when] left untreated, depression is potentially fatal,” Bill Martin, J&J’s global therapeutic area head of neuroscience, said in an interview. 

Around one-third of the estimated 21 million U.S. adults with major depression battle symptoms — such as persistent feelings of sadness, sleep disturbances, low energy and thoughts of death or suicide — that don’t respond to treatment, according to some estimates. 

“For the first time ever, we now have an option that gives patients freedom,” said Dr. Gregory Mattingly, a physician and president of the Midwest Research Group who was involved in Spravato’s original clinical trials. 

His center in St. Louis, Missouri, has treated more than 6,000 patients with the drug, and currently just over 100 people are taking it there. That is one of 3,000 outpatient treatment centers in the U.S. that are certified to administer Spravato, according to J&J’s tally.

Mattingly said patients can now choose to take Spravato with or without an oral antidepressant, especially if those pills aren’t improving their symptoms and are causing undesirable side effects, such as weight gain and sexual issues. 

J&J’s Martin said the approval provides “an avenue for caregivers and their patients to really optimize, personalize the treatment paradigm for each individual” and determine the best way for them to manage the disease. 

That could potentially “open up the number of patients who could benefit” from Spravato, according to Martin. 

Spravato is on its way to becoming a blockbuster product, with the drug bringing in $780 million in sales during the first nine months of 2024 as doctors grow more comfortable using it, according to J&J’s third-quarter earnings. The company has even higher expectations for its growth, telling investors in December that it expects sales will increase to between $1 billion and $5 billion annually. 

That is a boon to J&J as it prepares for an upcoming patent expiration and new negotiated prices with Medicare to pressure sales of its top-selling inflammatory treatment, Stelara. 

The approval is based on a phase four trial, which showed that Spravato alone improved depressive symptoms beginning about 24 hours after treatment and lasting through at least one month. The company has said that the safety profile was consistent with previous clinical data on Spravato’s use in combination with oral antidepressants.

Martin said that demonstrates “not only rapid symptom relief, but also a durable symptom relief” when patients take Spravato by itself. 

Spravato blazed a new trail in 2019 as the first new major depression treatment to win FDA approval in more than three decades. The drug is related to ketamine, a common anesthetic that can have hallucinogenic effects and is sometimes misused recreationally. J&J made it into a nasal spray to get it into the brain quickly. 

Spravato “turns on neural networks in a way that’s different,” said Mattingly. 

“Our standard oral antidepressants took weeks to months to see if they’re going to work,” he added. “Quite often with the same day, the very next day, the very next day, people can already start to feel they’re feeling somewhat better” with Spravato.

Spravato’s warning label cautions about the risk of sedation and dissociation, respiratory depression, suicidal thoughts and abuse or misuse of the drug, among other potential side effects. Because of that, Spravato is only available through a restricted program, meaning it can’t be purchased at a pharmacy and is only administered in certified health-care settings under strict supervision. 

Users of the medication must also be monitored by a health-care professional for two hours following administration.

Spravato’s launch had a sluggish start, especially as pandemic-related challenges complicated arrangements for the drug’s necessary medical supervision. But J&J began to market Spravato more heavily after in-person doctor visits became the norm again, and physicians became more aware of its benefits. 

“The mental health community wasn’t really used to doing procedures at that point. We weren’t used to having a space set aside. We weren’t used to thinking about how to do Spravato,” Mattingly said. “I think the good news is now we’ve all seen the benefits to our patients. So many of us have become really strong advocates” for it. 

Five years of real-world data on the drug and a head-to-head study demonstrating Spravato’s superior efficacy to an oral antidepressant also gave doctors higher confidence in the treatment, according to J&J’s Martin.