Originally published 23 Jan 25
The U.S. Food and Drug Administration has approved Spravato (esketamine) CIII nasal spray for adults living with major depressive disorder who have had an inadequate response to at least two oral antidepressants, according to a news release issued by Johnson & Johnson.
Spravato is the first and only approved monotherapy for adults with refractory major depressive disorder. Approval of Spravato, granted following FDA priority review, was based on the results of a randomized, double-blind, multicenter, placebo-controlled trial. On day 28 of the trial, patients taking Spravato exhibited numerical improvements for all 10 items on the Montgomery-Asberg Depression Rating Scale (MADRS). After four weeks, 22.5 percent of patients taking Spravato achieved remission (score ≤12 on MADRS) compared with 7.6 percent of patients taking placebo.
Spravato nasal spray is administered by the patient under the supervision of a health care provider in a health care setting. Spravato targets the neurotransmitter glutamate; however, the mechanism by which esketamine exerts its antidepressant effect is unknown. In an effort to ensure the safe and appropriate use of Spravato, the medication is only available through a restricted program called the Spravato Risk Evaluation and Mitigation Strategy Program. This is due to the risks for serious adverse outcomes resulting from sedation, dissociation, respiratory depression, abuse, and misuse.
Here are the basics:
Spravato® (esketamine) nasal spray is an innovative FDA-approved medication designed to treat adults with treatment-resistant depression (TRD) who have not responded to at least two other antidepressant therapies, as well as those with major depressive disorder (MDD) experiencing suicidal thoughts or actions. Unlike traditional antidepressants, which primarily target serotonin or norepinephrine, Spravato works as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, modulating the glutamate system in the brain to provide rapid relief. This unique mechanism allows some patients to experience improvement in depressive symptoms within hours or days, making it a valuable option for those in urgent need of relief.
Administered as a nasal spray, Spravato is taken under the supervision of a healthcare provider in certified treatment centers to ensure safety and proper monitoring. The treatment regimen typically begins with twice-weekly doses during the first four weeks, followed by a maintenance phase with less frequent dosing. Due to potential side effects such as dissociation, dizziness, sedation, and increased blood pressure, patients are monitored for at least two hours after each administration. Spravato is not recommended for individuals with certain medical conditions, including aneurysmal vascular disease or uncontrolled hypertension.
To ensure safe use, Spravato is available only through a restricted distribution program called the Spravato REMS (Risk Evaluation and Mitigation Strategy). This program helps healthcare providers and patients navigate the treatment process while minimizing risks. By offering a rapid-acting alternative for severe depression, Spravato represents a significant advancement in mental health care, providing hope for patients who have not found success with conventional therapies.