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 Peer reviewed DOI: 10.3389/fpsyt.2026.1766485 via PubMed
Summary
Ketamine may offer potential benefits for treating negative and depressive symptoms in patients with schizophrenia, despite the absence of randomized controlled trials. While some concerns exist regarding its psychotropic effects, individual case reports suggest that ketamine can provide antidepressant effects without exacerbating psychotic symptoms. The review discusses both the advantages and risks associated with ketamine use in this population.
Study at a glance
| Design | review |
|---|---|
| Population | patients with schizophrenia and depressive symptoms |
| Key finding | Ketamine may provide antidepressant effects without provoking psychotic symptoms in patients with severe psychotic depression and schizophrenia. |
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.