FDA

Esketamine nasal spray approved as monotherapy for treatment-resistant depression

January 23, 2025

FDA approved Spravato (esketamine) nasal spray for use as monotherapy for adults with treatment-resistant depression (TRD).

The non-competitive N-methyl D-aspartate (NMDA) receptor antagonist was previously approved for use in conjunction with an oral antidepressant for 1) TRD in adult and 2) depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.

Efficacy

Approval of the new monotherapy indication was supported by data from the phase 4 TRD4005 trial (NCT04599855) in which esketamine nasal spray alone led to rapid and superior improvement in Montgomery-Asberg Depression Rating Scale (MADRS) total score compared with placebo. In a post-hoc analysis, esketamine nasal spray demonstrated numerical improvements across all 10 MADRS items at day 28. At week 4, 22.5% of esketamine nasal spray recipients achieved remission (defined as MADRS total score ≤12) compared with 7.6% of placebo recipients.

Safety

The most common adverse events reported with esketamine monotherapy were dissociation, nausea, dizziness, headache, anxiety, vomiting, feeling drunk, increased BP, and sedation. No new safety signals were identified.

Due to risks of serious adverse outcomes resulting from sedation, dissociation, respiratory depression, abuse, and misuse, Spravato is only available through the Spravato Risk Evaluation and Mitigation Strategy (REMS) Program. The drug must be administered intranasally under direct supervision of an HCP.

Sources:

SPRAVATO® (esketamine) approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression. Johnson & Johnson. 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

Spravato. Package insert. Johnson & Johnson. 2025. Accessed January 22, 2025. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf