At least 21 million adults in the United States have experienced Depression. And while oral antidepressants are a common treatment, they don’t work for everyone. Now the Food and Drug Administration (FDA) has extended approval for Johnson & Johnson’s nasal spray, Spravato, to be used as a stand-alone treatment for people with severe depression who have not been helped by other treatment methods.
You were good previously approved by the FDA in 2019 for treatment-resistant depression, but it was required to be used with an oral antidepressant. The new FDA approval means that people can use the nasal spray as is to treat depression. This means there is no need to take an oral antidepressant with it.
That said, Spravato is a tightly controlled drug, and getting it isn’t as simple as visiting your local pharmacy. Here’s what doctors want you to know about Spravato, plus potential side effects to be aware of.
Experts featured in this article:
Thea GallagherPsyD, is a clinical associate professor at NYU Langone Health and co-host of the Mind in View podcast.
Gail SaltzPsyD, is Associate Professor of Psychiatry at NY Presbyterian Hospital Weill-Cornell School of Medicine.
Yvette ShelineMD, is director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania Perelman School of Medicine.
Amir AfkhamiMD, PhD, is Professor and Vice Chair of the Department of Psychiatry at the George Washington University Milken Institute School of Public Health.
David MerrillMD, PhD, is a psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and the Singleton Endowed Chair in Integrative Brain Health.
What is Spravato, the anti-depression nasal spray?
Spravato is the brand name for esketamine, a chemical form of the anesthetic ketamine, according to Thea Gallagher, PsyD, a clinical associate professor at NYU Langone Health and cohost of Mind in View podcast. The drug is “ketamine-related, but not ketamine,” explains Gail Saltz, MD, associate professor of psychiatry at NY Presbyterian Hospital Weill-Cornell School of Medicine. Ketamine is historically a party drug also nicknamed “Special K” – but it has also been used off-label intravenously at some wellness clinics in an attempt to alleviate symptoms of depression. Unlike Spravato, this use of ketamine has not been approved by the FDA.
“The data show that Spravato is really effective for treatment-resistant depression,” says Dr. Gallagher. Previous research cited by FDA found that the nasal spray showed a “statistically significant effect” on severe depression compared to those taking a placebo, and the effect of the drug was seen within two days of the first dose for some.
“Spravato is intended to be administered under the direct supervision of a healthcare provider,” said Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania Perelman School of Medicine. Because Spravato carries a risk of abuse, it is only available through a limited distribution system under a Risk Evaluation and Mitigation Strategy (REMS). This means that you must go to a specialized treatment center and use the drug under the supervision of a licensed health care provider.
After taking Spravato, you must be observed for at least two hours at the treatment center while you are monitored for any side effects, according to official website of the drug.
How does Spravato work?
Spravato works on a pathway in the brain that affects glutamate, a neurotransmitter in the brain that may play a role in depression. “It targets a different system in the brain than the typical antidepressant,” says Dr. Gallagher.
Spravato increases the release of glutamate, which ultimately boosts mood by improving brain connectivity, says Amir Afkhami, MD, PhD, professor and vice chair of the Department of Psychiatry at the George Washington University Milken Institute School of Public Health.
“Unlike existing drugs for depression, esketamine does not directly involve serotonin, norepinephrine, or dopamine reuptake,” said Dr. Sheline.
But it’s not entirely known why Spravato works in people with treatment-resistant depression — research just shows that it does. One thing we do know: It acts quickly. “What differentiates Spravato from traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs) is that it has a relatively rapid onset of action,” said Dr. Afkhami. “Traditional antidepressants usually take weeks to work. With Spravato, you’ll see the antidepressant effect sometimes within hours or a day.”
Who is Spravato best for?
Spravato is designed to be used by people with major depression who have not responded well to previous treatments. The FDA specifically requires that patients have an “inadequate response” to at least two oral antidepressants before they qualify for Spravato.
Right now this is only approved for use in adults: The Made a website notes that it is not currently known whether the drug is safe or effective in children.
Potential risks with Spravato
Spravato has a list of potential side effects, including disassociation, dizziness, nausea, sedation, dizziness, decreased sensation or sensitivity, anxiety, lethargy, increased blood pressure, vomiting, and feeling intoxicated, according to FDA.
It also comes with a risk of high blood pressurewhich is one of the reasons why patients are closely monitored after receiving the drug, says Dr. Afkhami. Spravato is also not recommended for expectant or breastfeeding mothers.
Another caveat: “One must remember that this is a potentially addictive drug that can create dependence, abuse, and withdrawal, and must therefore be handled carefully,” says Dr. Saltz. Because Spravato comes with a risk of addiction, it is highly regulated, says David Merrill, MD, PhD, psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and Singleton Endowed Chair in Integrative Brain Health.
“It’s involved and getting Spravato involves a lot of effort,” he says. “But safety is important. We’ve seen the fallout socially of someone using ketamine unsupervised.” (Friends star Matthew Perry died of one ketamine overdose in 2023. He had previously used an infusion form of ketamine in therapy for depression.)
If you think Spravato might be right for you, Dr. Saltz recommends you talk to a healthcare provider about next steps. “You need to be evaluated by a psychiatrist who is familiar with and uses ketamine and ketamine-related products to treat depression,” she says. They will be able to help you decide if this treatment option is the best for you.
Corinne Miller is a writer specializing in general wellness, health and lifestyle trends. Her work has appeared in Women’s Health, Self, Health, Forbes and more.
