FDA Approves Esketamine Nasal Spray for Treatment-Resistant Depression

The FDA has approved esketamine (Spravato) nasal spray as a monotherapy for adults with treatment-resistant depression. This approval applies to individuals who have had an inadequate response to at least two oral antidepressants. The announcement was made by the drug’s manufacturer, Johnson & Johnson, on Tuesday.

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 (TRD).

“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. “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.”

This approval, which was granted following FDA Priority Review, is supported by positive results from the randomized, double-blind, multicenter, placebo-controlled study in which SPRAVATO® alone showed a rapid and superior improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score vs. placebo. In a post-hoc analysis, SPRAVATO® demonstrated numerical improvements across all 10 MADRS items at day 28.2 At week 4, 7.6% of patients taking placebo and 22.5% of patients taking SPRAVATO® achieved remission (MADRS total score ≤ 12).1 The safety profile of SPRAVATO® as a standalone treatment was consistent with the existing body of clinical and real-world data when used in conjunction with an oral antidepressant, and no new safety concerns were identified.

Because of the risks of serious adverse outcomes resulting from sedation, dissociation, respiratory depression, abuse, and misuse, to facilitate safe and appropriate use, SPRAVATO® is only available through a restricted program called the SPRAVATO® Risk Evaluation and Mitigation Strategy (REMS) Program.

“For more than six years, I’ve seen firsthand the real-world impact SPRAVATO® can have on patients’ lives,” said Gregory Mattingly, M.D., President, Midwest Research Group and Founding Partner St. Charles Psychiatric Associates. “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.”

SPRAVATO® is unique and works by targeting glutamate, which is the most abundant excitatory neurotransmitter in the brain.6 The mechanism by which esketamine exerts its antidepressant effect is unknown.

Backed by more than a decade of research and almost six years of real-world evidence, SPRAVATO® has proven to be a transformational treatment option for many patients with TRD by reducing depression symptoms in as little as 24 hours and reducing the time to relapse for patients who stay on treatment. To date, SPRAVATO® has been administered to more than 140,000 patients worldwide.

Depression is a common mental health disorder that impacts an estimated 280 million people worldwide.3 In the U.S., approximately 21 million adults have had at least one major depressive episode. Approximately one-third of adults with MDD will not respond to oral antidepressants alone and are considered to have treatment-resistant depression (TRD), which is defined as inadequate response to two oral medications.4,5 TRD has a significant negative impact on the lives of those affected and has one of the highest economic burdens of all psychiatric disorders.5 Patients often cycle through multiple oral medications, waiting 4-6 weeks for potential relief. After trying their third oral antidepressant, approximately 86% of patients do not achieve remission.

SPRAVATO® (esketamine) CIII nasal spray is approved by the U.S. Food and Drug Administration alone or in conjunction with an oral antidepressant for adults with MDD when they have inadequate response to at least two oral antidepressants (TRD) and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior in conjunction with an oral antidepressant. It is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and is believed to work differently by acting on a pathway in the brain that affects glutamate. The mechanism by which esketamine exerts its antidepressant effect is unknown. To date, SPRAVATO® has been approved in 77 countries and administered to more than 140,000 patients worldwide.