FDA advisory committees recommend approval of esketamine nasal spray for treatment-resistant depression

Cross-posted from our Optum Insights blog.

Two advisory committees of the U.S. Food and Drug Administration (FDA) recently voted to approve esketamine nasal spray for the treatment of adults with treatment-resistant depression (TRD), which is typically defined as failing trials of at least two antidepressant treatments for major depressive disorder. Esketamine is chemically related to ketamine, a general anesthetic used off-label in pain management to treat various neuropathic pain conditions, such as complex regional pain syndrome. Esketamine is believed to have a new mechanism of action and thought to work differently than currently available medications for major depressive disorder and TRD.

Context for ketamine and esketamine

Although ketamine is used off-label in workers’ compensation for the treatment of neuropathic pain, through topical compounded medications and by intravenous infusion, there is not enough evidence to support its use for the treatment of pain. Intravenous ketamine has also been used off-label for the treatment of depression even though its safety and effectiveness are not well-studied. In addition, ketamine is known as a medication of abuse.

Despite being related to ketamine, the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted to approve esketamine nasal spray for the treatment of TRD. The decision to recommend its approval was based on data from five Phase 3 clinical studies in patients with a history of inadequate response to at least two prior antidepressants and having severe symptoms.

Two of the five studies provided the most evidence to support its effectiveness and showed that treatment with esketamine nasal spray, plus a newly initiated oral antidepressant, resulted in rapid and sustained improvement of depressive symptoms compared to placebo nasal spray combined with a newly initiated oral antidepressant.

Strategy to address potential risks

If ultimately approved by the FDA, esketamine nasal spray will be classified as a Schedule III controlled substance and labeled as Spravato™, marketed under Johnson and Johnson’s pharmaceutical unit Janssen. To address the potential for adverse events, which reportedly may occur within the first two hours of administration (e.g., sedation and increased blood pressure), the committees recommended a Risk Evaluation and Mitigation Strategy (REMS) requiring administration to occur only in healthcare settings, where patients could be monitored closely for at least two hours.

Next steps for esketamine

The FDA is not bound by the recommendations of its advisory committees and will consider their guidance during its review. The FDA is expected to make its decision as early as March 4, 2019. Since this nasal spray is intended to be prescribed for those with TRD who have failed other antidepressants, it is unlikely to be considered first-line therapy. If approved by the FDA, Spravato will be reviewed by our Pharmacy and Therapeutics Committee to determine its status on all of our standard formularies.

For more information on the FDA announcement, please click here.

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  1. FDA Advisory Committee Recommends Approval of SPRAVATO™ (esketamine) Nasal Spray CIII for Adults with Treatment-Resistant Depression [news release]. Titusville, New Jersey; February 12, 2019: Janssen website. https://www.janssen.com/fda-advisory-committee-recommends-approval-spravato-esketamine-nasal-spray-ciii-adults-treatment. Accessed February 20, 2019.
  2. MPR. FDA Committees Vote on Esketamine Nasal Spray for Treatment-Resistant Depression [news release]. February 13, 2019. Available at: https://www.empr.com/home/news/drugs-in-the-pipeline/fda-committees-vote-on-esketamine-nasal-spray-for-treatment-resistant-depression/. Accessed February 20, 2019.