Ketamine Treatment for Depression in Patients With a History of Psychosis or Current Psychotic Symptoms: A Systematic Review

J Clin Psychiatry. 2021 Jul 13;82(4):20r13459. doi: 10.4088/JCP.20r13459.


Objective: Ketamine shows rapid and robust antidepressant effects in clinical studies. Psychotic features are an exclusion criterion in most ketamine treatment studies based on the assumption that psychosis will increase with ketamine administration. As patients with treatment-resistant depression (TRD) often have psychotic features, and treatment-resistant depressive symptoms are also common in patients with schizophrenia, the aim of this systematic review is to determine whether this assumption holds true.

Data Sources: The literature was searched for data on ketamine treatment for depression or negative symptomatology in patients with a history of psychosis or current psychotic symptoms (PubMed/MEDLINE) from inception to March 2020 without date or language restrictions. The following terms were used: ketamine and psychosis, psychotic or schizo*. A filter for human studies was applied.

Study Selection: A total of 482 articles were identified; 473 articles were excluded because they did not report on the effect of ketamine treatment in patients with a history of psychosis or current psychotic symptoms.

Data Extraction: The remaining 9 articles were reviewed.

Results: Nine reports of pilot studies and case reports with a total of 41 patients have been published. These studies suggest that short-term ketamine treatment for depression and even negative symptoms in patients with a history of psychosis or current psychotic features can be both safe and effective, as side effects were mild and self-limiting.

Conclusions: The currently available literature does not support the assumption that ketamine will exacerbate psychotic symptoms in predisposed patients. Data, however, are limited, and further trials are needed in this patient group.

Publication types

  • Systematic Review

MeSH terms

  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / adverse effects
  • Depression / complications
  • Depression / drug therapy*
  • Humans
  • Ketamine / administration & dosage*
  • Ketamine / adverse effects
  • Psychotic Disorders / complications


  • Antidepressive Agents
  • Esketamine
  • Ketamine