Ketamine for depression: what changed, 2000 to 2025
A small trial in 2000 first showed ketamine's rapid antidepressant effect. The FDA approved esketamine nasal spray in 2019, added a second indication in 2020, and approved it as a stand-alone treatment in 2025. Large trials have compared ketamine with ECT, while the FDA warned in 2023 about unsupervised compounded ketamine.
A sourced timeline of ketamine in mental health: the first depression trial, esketamine approvals, the PTSD and ECT trials, and the FDA's warning on compounded ketamine.
From anesthetic to approved depression treatment, step by step.
Key takeaways
- Approvals have covered esketamine only; IV ketamine for depression remains off-label.
- Research has expanded from depression to PTSD and other conditions.
- Regulators have warned about compounded, unsupervised use.
What to watch next
Longer-term studies of benefit and safety, more trials for conditions such as PTSD, and any change in how compounded and telehealth ketamine is regulated. This page will be updated as each happens.
Frequently asked questions
When was ketamine first approved?
Ketamine was approved decades ago as an anesthetic. For depression, only esketamine nasal spray is FDA-approved, first in March 2019.
Related on Beiing
- The four kinds of ketamine - Where each stands today.
- Ketamine for mental health - The hub for every page in this guide.
Sources
- Berman RM, et al. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 2000 - U.S. National Library of Medicine
- FDA approves esketamine nasal spray for hard-to-treat depression (March 2019) - Healio Psychiatry
- FDA okays new indication for esketamine nasal spray (August 2020) - MDedge
- Repeated ketamine infusions reduce symptom severity in chronic PTSD (Feder et al., American Journal of Psychiatry, January 2021) - Icahn School of Medicine at Mount Sinai
- Ketamine comparable to ECT for many patients with refractory depression (ELEKT-D trial, New England Journal of Medicine, 2023) - Psychiatric News (American Psychiatric Association)
- FDA warns patients and health care providers about potential risks associated with compounded ketamine products, including oral formulations, for the treatment of psychiatric disorders (October 2023) - U.S. Food and Drug Administration
- SPRAVATO approved in the U.S. as the first and only monotherapy for adults with treatment-resistant depression (21 January 2025) - Johnson & Johnson (manufacturer press release)
Written by Beiing Editorial Team · Editorially reviewed by Beiing Editorial & Research Review · Published · Last reviewed . Editorial and research review by Beiing writers and researchers. This is not medical or clinical review, and no clinician signs off on our content.
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