Ketamine for negative and depressive symptoms in schizophrenia: the evidence so far.
C M Diendorfer, C Bum, Ana Weidenauer, U Sauerzopf, Lucie Bartova, I Dajic, L Müller, Dan Rujescu, N Praschak-Rieder, M Willeit
Frontiers in Psychiatry 2026 DOI: 10.3389/fpsyt.2026.1766485 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Randomized Peer reviewed |
|---|---|
| Topics | Ketamine Esketamine |
| Keywords | Depressive symptoms Glutamate Negative symptoms schizophrenia |
| Key findings | 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.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cites 25
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Recent advances in the phencyclidine model of schizophrenia American Journal of Psychiatry October 1, 1991
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
and 20 more in the library