What to Know About Spravato, the Nasal Spray For Depression

At least 21 million adults in the U.S. have experienced depression. And, while oral antidepressant medications are a common treatment, they don't work for everyone. Now, the Food and Drug Administration (FDA) has expanded approval for Johnson & Johnson's nasal spray, Spravato, to be used as a standalone treatment for people with severe depression who haven't been helped by other treatment methods.

Spravato was 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 people can use the nasal spray as-is to treat depression. Meaning, there's no need to take an oral antidepressant with it.

That said, Spravato is a tightly controlled medication, 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 Gallagher, PsyD, is a clinical associate professor at NYU Langone Health and cohost of the Mind in View podcast.

Gail Saltz, PsyD, is an associate professor of psychiatry at the NY Presbyterian Hospital Weill-Cornell School of Medicine.

Yvette Sheline, MD, is the director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania Perelman School of Medicine.

Amir Afkhami, MD, PhD, is a professor and vice chair of the department of psychiatry in the George Washington University Milken Institute School of Public Health.

David Merrill, MD, PhD, is a psychiatrist at Providence Saint John's Health Center in Santa Monica, CA, and Singleton Endowed Chair in Integrative Brain Health.

What Is Spravato, the Nasal Spray For Depression?

Spravato is the brand name for esketamine, a chemical form of the anesthetic drug ketamine, according to Thea Gallagher, PsyD, a clinical associate professor at NYU Langone Health and cohost of the Mind in View podcast. The drug is “ketamine related, but not ketamine,” explains Gail Saltz, MD, associate professor of psychiatry at the NY Presbyterian Hospital Weill-Cornell School of Medicine. Ketamine is historically a recreational party drug that also has the nickname “Special K” — but it has also been used off-label intravenously in some wellness clinics in an attempt to mitigate symptoms of depression. Unlike Spravato, this usage of ketamine has not been FDA approved.

“The data show Spravato is really effective for treatment-resistant depression,” Dr. Gallagher says. Previous research cited by the FDA found that the nasal spray showed a “statistically significant effect” on severe depression compared to those who took 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 direct supervision by a healthcare provider,” says Yvette Sheline, MD, director of the Center for Neuromodulation in Depression and Stress at the University of Pennsylvania Perelman School of Medicine. Because Spravato comes with the potential for misuse, it's only available through a restricted distribution system under a Risk Evaluation and Mitigation Strategy (REMS). Meaning, you have to go to a specialty treatment center and use the medication under the supervision of a licensed healthcare provider.

After you take Spravato, you have to be observed for at least two hours at the treatment center while you're monitored for possible side effects, according to the drug's official website.

How Does Spravato Work?

Spravato acts on a pathway in the brain that impacts 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,” Dr. Gallagher says.

Spravato increases the release of glutamate, ultimately boosting mood by enhancing brain connectivity, says Amir Afkhami, MD, PhD, a professor and vice chair of the department of psychiatry in 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,” says 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 sets Spravato apart from traditional antidepressants such as selective serotonin reuptake inhibitors (SSRIs) is that it has a relatively rapid onset of action,” Dr. Afkhami says. “Traditional antidepressants usually take weeks to show effect. 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 depressive disorder who haven't responded well to previous treatments. The FDA specifically requires patients to have an “inadequate response” to at least two oral antidepressants before qualifying for Spravato.

Right now, this is just approved for use in adults: The Spravato website notes that it's not currently known if the drug is safe or effective in children.

Potential Risks of Spravato

Spravato has a list of potential side effects, including disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity, anxiety, lethargy, increased blood pressure, vomiting, and feeling drunk, per the FDA.

It also comes with a risk of high blood pressure, which is one of the reasons why patients are closely monitored after receiving the drug, Dr. Afkhami says. Spravato is also not recommended for expectant or breastfeeding moms.

Another warning: “One must keep in mind this is a potentially addictive drug that can create dependence, abuse, and withdrawal, and so must be carefully managed,” Dr. Saltz says. Because Spravato comes with a risk of dependency, it's 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 from a ketamine overdose in 2023. He had previously used an infusion form of ketamine in therapy for depression.)

If you think Spravato may be right for you, Dr. Saltz recommends contacting a healthcare provider about next steps. “One needs to be evaluated by a psychiatrist who is familiar with and uses ketamine, and ketamine-related products, to treat depression,” she says. They'll be able to help you decide if this treatment option is the best for you.

Korin 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.