FDA approves Spravato as monotherapy for adults with major depressive disorder

Key takeaways:

• Spravato is the first monotherapy for adults with major depressive disorder who had an inadequate response to at least two oral antidepressants.
• It is available only through a restricted REMS program.  

The FDA has approved a supplemental new drug application for Spravato, an esketamine nasal spray that can be used as monotherapy for adults with treatment-resistant depression, Johnson & Johnson announced in a press release.

According to the release, Spravato (esketamine, Johnson & Johnson/Janssen) CII nasal spray, a nonselective, noncompetitive antagonist of the N-methyl-D-aspartate receptor, is the first and only monotherapy for adults with major depressive disorder who have had inadequate response to at least two oral antidepressants.

“Treatment-resistant depression can be very complicated, especially for patients who do not respond to oral antidepressants or cannot tolerate them,” Bill Martin, PhD, global therapeutic area head of neuroscience at Johnson & Johnson Innovative Medicine, said in the release. “Spravato is now available as a standalone treatment, meaning patients may experience improvements in depressive symptoms as early as 24 hours and at 28 days, without the need for daily oral antidepressants.”

The approval, which followed FDA priority review of a supplemental new drug application submitted in July 2024, stemmed from results of a randomized, double-blind, multicenter, placebo-controlled clinical trial, which showed that Spravato monotherapy demonstrated rapid, superior improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score compared with placebo.

Further, the company reported that in a post-hoc analysis, 22.5% of patients in the treatment group achieved remission (MADRS total score 12) vs. 7.6% of patients in the placebo at week 4. Spravato demonstrated improvements across all 10 MADRS items at day 28, and, as a standalone treatment, maintained a safety profile consistent with existing data when used with an oral antidepressant.

No new safety concerns were identified, the release stated.

Due to the risk for serious adverse outcomes linked to sedation, dissociation, respiratory depression, abuse and misuse, Spravato is available only through the restricted Spravato Risk Evaluation and Mitigation Strategy (REMS) Program.