Also called: ketamine-assisted psychotherapy (KAP)
Ketamine-assisted therapy combines psychotherapy with one or more sessions of ketamine, an anesthetic that at lower doses can ease depressive symptoms within hours and brings on a feeling of detachment called dissociation. It is a treatment approach, not a diagnosis, and practices vary widely in dose, route and how much therapy is given.
Where it comes from
Ketamine was approved in the US as an anesthetic in 1970. A 1997 review summarized ten years of work on ketamine-assisted psychotherapy for alcohol dependence, and in 2000 a small placebo-controlled study in seven people found that one infusion relieved depressive symptoms within three days. In a 2006 trial in treatment-resistant depression, 71 percent of patients responded the day after an infusion, but only 35 percent still did a week later.
What is approved and what is not
In March 2019 the FDA approved esketamine nasal spray, sold as Spravato, for treatment-resistant depression. It is also approved for depressive symptoms with acute suicidal thoughts, and since January 2025 it may be used on its own, without an oral antidepressant, for treatment-resistant depression. It is given only in certified settings, with monitoring for at least two hours after each dose. Ketamine itself is not FDA-approved for any psychiatric disorder; clinics use it off-label, and in 2023 the FDA warned about compounded ketamine taken at home without monitoring.
What the evidence shows
In a phase 3 trial of 227 patients, esketamine plus a new antidepressant lowered depression scores by 4.0 points more than the antidepressant with a placebo spray after four weeks, on a 60-point scale. Whether therapy adds to ketamine’s effect is less clear. A 2023 review of 19 studies with 1,006 patients found mostly positive results but too much variation for firm conclusions. In a trial of 96 people with severe alcohol use disorder, three ketamine infusions led to more days without alcohol at six months, most of all when paired with therapy, but relapse rates did not differ.
Risks
The esketamine label carries a boxed warning for sedation, dissociation, slowed breathing, misuse and, as with all antidepressants, suicidal thoughts in young people. Blood pressure rises for about four hours after a dose, and long-term ketamine use or misuse has been linked to bladder damage. Our residencies use psilocybin rather than ketamine, and our FAQ compares the two.
Related terms
Psilocybin: the compound used in most psychedelic therapy trials.
Psychedelic Integration: the work that follows a session.
Ego Dissolution: a dissolving sense of self, which ketamine can also produce.
Sources
US Food and Drug Administration - Spravato (esketamine) nasal spray, prescribing information, 2025 (indications, boxed warning, blood pressure, bladder)
US Food and Drug Administration - Supplement approval letter NDA 211243/S-016 (monotherapy), 2025 (January 2025)
US Food and Drug Administration - Compounding risk alerts (ketamine alert of October 10, 2023) (ketamine not approved for any psychiatric disorder)
Krupitsky & Grinenko - Ketamine psychedelic therapy (KPT): A review of the results of ten years of research, Journal of Psychoactive Drugs, 1997 (alcohol dependence)
Berman et al. - Antidepressant effects of ketamine in depressed patients, Biological Psychiatry, 2000 (7 patients)