Key takeaway
Esketamine became the first FDA-approved ketamine-based treatment for depression. Here is what the trials found.
What is Spravato? Spravato is a nasal spray containing esketamine, a form of the ketamine molecule. The FDA approved it in 2019 for treatment-resistant depression, used alongside an oral antidepressant, and later for depressive symptoms in adults with major depression and suicidal thoughts or actions. In 2025 it was also approved for use on its own.
Key trials - TRANSFORM-2: Adults who added esketamine to a new oral antidepressant improved more after four weeks than those who added a placebo spray. - SUSTAIN-1: People who responded and continued esketamine were significantly less likely to relapse than those switched to placebo. - ESCAPE-TRD (2023, NEJM): Esketamine led to more remission at eight weeks than quetiapine extended-release, a common add-on medication.
How treatment works Spravato is given in a certified clinic under supervision, with at least two hours of monitoring after each dose. Many insurers cover it with prior authorization.
Sources: Popova V, et al. Am J Psychiatry 2019; Daly EJ, et al. JAMA Psychiatry 2019; Reif A, et al. N Engl J Med 2023. Educational only.
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