FDA Approves Spravato as Monotherapy for Major Depressive Disorder

The FDA has approved esketamine (Spravato) for the treatment of major depressive disorder (MDD) in adult patients who have had inadequate response to at least 2 oral antidepressants, Johnson and Johnson announced in a release.¹ The decision makes Spravato the first and only monotherapy approved for adults living with the condition.

FDA Approves Spravato as Monotherapy for Major Depressive Disorder / Tada Images - stock.adobe.com

The approval was based on data from the phase 4 TRD4005 study (NCT04599855), in which the therapy showed a rapid and superior improvement in total score on the Montgomery-Asberg Depression Rating Scale (MADRS). The safety of Spravato as a monotherapy was also found to be consistent with the existing body of clinical and real-world data, with no new safety concerns being identified in the study.

READ MORE: Pharmacy Screening Can Identify Depression in Older Adults

“For more than 6 years, I’ve seen firsthand the real-world impact Spravato can have on patients’ lives,” Gregory Mattingly, MD, president of Midwest Research Group and founding partner St. Charles Psychiatric Associates, said in a release.¹ “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.”

The TRD4005 study was a randomized, double-blind, multicenter, place-controlled phase 4 trial that evaluated the efficacy, safety and tolerability of Spravato as a monotherapy in adults living with MDD. The study cohort included 477 patients who randomly received 56 mg Spravato, 84 mg Spravato or a placebo. Patients were followed for 4 weeks and changes in symptoms were assessed via the MADRS from baseline through day 28.

The study found treatment with Spravato resulted in rapid change in MADRS total score as early as 24 hours after the first dose and was sustained through at least 4 weeks of treatment. At day 28, patients treated with the therapy showed improvements across all 10 MADRS items. And at week 4, 22.5% of patients taking the therapy achieved remission, compared to 7.6% of patients who received placebo.

“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,” Bill Martin, PhD, Global Therapeutic Area Head of Neuroscience at Johnson & Johnson Innovative Medicine, said in a release.¹ “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.”

Spravato is an esketamine nasal spray that is absorbed into the blood stream through the nasal passages. It works on the ionotropic glutamate receptor N-methyl-D-aspartate (NMDA) in the brain. However, the mechanism by which it exerts its antidepressant effect is not known. The therapy is only available through a restricted program due to the risks of serious adverse outcomes resulting from sedation, dissociation, respiratory depression, abuse, and misuse.

Spravato was initially approved by the FDA in March 2019 for use in conjunction with an oral antidepressant in adults with treatment-resistant depression. The therapy used the first new mechanism of action in decades to treat MDD.² In 2020, the FDA approved a supplemental new drug application for Spravato to treat depressive symptoms in adults with MDD who have acute suicidal ideation or behavior.³

READ MORE: Mental and Behavioral Health Resource Center

References

1. SPRAVATO^® (esketamine) approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression. News Release. J&J. January 21, 2025. Accessed January 21, 2025. https://www.jnj.com/media-center/press-releases/spravato-esketamine-approved-in-the-u-s-as-the-first-and-only-monotherapy-for-adults-with-treatment-resistant-depression

2. Janssen Announces U.S. FDA Approval of SPRAVATO^TM (esketamine) CIII Nasal Spray for Adults with Treatment-Resistant Depression (TRD) Who Have Cycled Through Multiple Treatments Without Relief. News Release. J&J. March 5, 2019. Accessed January 21, 2025. https://www.jnj.com/media-center/press-releases/janssen-announces-u-s-fda-approval-of-spravatotm-esketamine-ciii-nasal-spray-for-adults-with-treatment-resistant-depression-trd-who-have-cycled-through-multiple-treatments-without-relief

3. Janssen Announces U.S. FDA Approval of SPRAVATO^® (esketamine) CIII Nasal Spray to Treat Depressive Symptoms in Adults with Major Depressive Disorder with Acute Suicidal Ideation or Behavior. News Release. J&J. August 3, 2020. Accessed January 21, 2025. https://www.jnj.com/media-center/press-releases/janssen-announces-u-s-fda-approval-of-spravato-esketamine-ciii-nasal-spray-to-treat-depressive-symptoms-in-adults-with-major-depressive-disorder-with-acute-suicidal-ideation-or-behavior