FDA Approves Esketamine as Monotherapy for Adults With Treatment-Resistant Depression
The approval of esketamine follows an FDA Priority Review and is based on data showing that esketamine alone demonstrated rapid and superior improvement in depressive symptoms compared with placebo.
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The US Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for esketamine (Spravato; Johnson & Johnson) CIII nasal spray as the first and only monotherapy for adults with major depressive disorder (MDD) who have not responded adequately to at least 2 oral antidepressants, according to a company news release.1
The approval follows an FDA Priority Review and is based on data showing that esketamine alone demonstrated rapid and superior improvement in depressive symptoms compared with placebo, beginning as early as 24 hours and meeting its primary endpoint at 4 weeks.1
"Treatment-resistant depression can be very complicated, especially for patients who do not respond to oral antidepressants or cannot tolerate them. For too long, healthcare providers have had few options to offer patients much-needed symptom improvement," said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience, Johnson & Johnson Innovative Medicine, in the news 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."1
In a randomized, double-blind, placebo-controlled study, esketamine led to statistically significant reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) total scores by day 28. A post-analysis revealed numerical improvements across all 10 MADRS items, and remission (MADRS ≤12) at week 4 was achieved by 22.5% of patients who received esketamine vs 7.6% of those in the placebo group. The safety profile of esketamine as monotherapy remained consistent with established clinical and real-world safety data, and no new concerns were identified.1
Because of the potential for sedation, dissociation, respiratory depression, and misuse, esketamine can be prescribed only through the Spravato Risk Evaluation and Mitigation Strategy (REMS) Program.1
According to Johnson & Johnson, approximately one-third of patients with MDD do not respond to oral antidepressants alone, underscoring the need for additional treatments. MDD is one of the most common psychiatric disorders, with an estimated 21 million adults in the U.S. living with the disease. About one-third of adults will not respond to oral antidepressants alone, which has a significant negative impact on the quality of life of those affected. MDD has a high economic burden, with nearly half of it attributable to treatment-resistant depression.2
"For more than six years, I've seen firsthand the real-world impact Spravatocan have on patients' lives," said Gregory Mattingly, M.D., President, Midwest Research Group and Founding Partner, St. Charles Psychiatric Associates, in the release release. "Now that it is also available as a monotherapy, healthcare providers have the freedom to further personalize treatment plans based on individual needs, so patients can experience the efficacy of SPRAVATO® in as little as 24 hours, through day 28, without the need for a daily oral antidepressant."1
Esketamine is a nonselective, noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, targeting the glutamate pathway. Although its exact antidepressant mechanism is unknown, esketamine has been administered to more than 140,000 patients worldwide and is approved in 77 countries.1
References
- Johnson & Johnson. SPRAVATO (esketamine) approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression [news release]. January 21, 2025. Accessed January 21, 2025. https://www.investor.jnj.com/news/news-details/2025/SPRAVATO-esketamine-approved-in-the-U.S.-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression/default.aspx
- National Institute of Mental Health. Major Depression. National Institute of Mental Health website. Accessed January 21, 2025. https://nimh.nih.gov/health/statistics/major-depression
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