Ketamine for negative and depressive symptoms in schizophrenia: the evidence so far.
C M Diendorfer, C Bum, A Weidenauer, U Sauerzopf, L Bartova, I Dajic, L Müller, D Rujescu, N Praschak-Rieder, M Willeit
Frontiers in psychiatry January 1, 2026 DOI: 10.3389/fpsyt.2026.1766485 via PubMed
Summary
AI-generated from the abstractKetamine, a drug used for treatment-resistant depression, may offer benefits for negative and depressive symptoms in schizophrenia, though no randomized controlled trials have tested it in psychotic disorders. Negative symptoms like apathy and anhedonia are hard to treat and often overlap with depression. Case reports show ketamine can improve mood without triggering psychosis, and its dissociative effects usually fade within one to two hours. This review examines ketamine's potential advantages and risks for schizophrenia patients, focusing on negative and depressive symptoms.
Study at a glance
| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Topics | Ketamine |
| Keywords | Depressive symptoms Glutamate Negative symptoms schizophrenia |
| Key finding | Ketamine may treat negative and depressive symptoms in schizophrenia without provoking psychosis, but no randomized controlled trials have been conducted. |
Abstract
Schizophrenia (SCZ) is a severe psychiatric condition characterized by positive symptoms such as hallucinations or delusions, as well as negative symptoms such as apathy, anhedonia and avolition. Given their chronic nature and limited response to current treatments, managing negative symptoms is a significant challenge for healthcare providers. Furthermore, many individuals with SCZ suffer from depressive symptoms during the course of their illness, which can be difficult to distinguish from negative symptoms as their clinical expression often overlaps. Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, has gained popularity as a rapid and effective treatment for treatment-resistant depression. So far, there have been no randomized controlled trials on the use of ketamine for depressive and negative symptoms in patients with psychotic disorders. However, while some authors have labeled the short-term psychotropic effects of ketamine as "psychotomimetic," individual case reports have shown promising antidepressant effects without provoking psychotic symptoms in patients with severe psychotic depression and SCZ. Ketamine-induced dissociative phenomena typically subsided spontaneously within one to two hours after administration. This review will primarily focus on potential advantages and risks of ketamine in patients with SCZ with a particular emphasis on its role as a possible treatment for negative and depressive symptoms.