Ketamine for psychotic depression: An overview of the glutamatergic system and ketamine's mechanisms associated with antidepressant and psychotomimetic effects.
Tuyen T. Le, Joshua D. Di Vincenzo, K. Teopiz, Yena Lee, D. Cha, L. Lui, Nelson B Rodrigues, R. Ho, Bing Cao, Kangguang Lin, F. Nasri, H. Gill, Orly Lipsitz, M. Subramaniapillai, R. Mansur, J. Rosenblat, R. Mcintyre
Psychiatry Research October 1, 2021 DOI: 10.1016/j.psychres.2021.114231 via Semantic Scholar
Summary
Psychotic depression, a severe form of major depression with hallucinations or delusions, affects 0.35-1% of people over a lifetime. Current treatments, such as antidepressants combined with antipsychotics or electroconvulsive therapy, often lead to relapse and side effects like tardive dyskinesia. Some case studies suggest ketamine may improve both mood and psychotic symptoms in treatment-resistant patients, but its safety is debated because ketamine can induce psychotomimetic effects. Most clinical trials have excluded these patients, so it remains unknown whether ketamine would worsen psychosis. Future research should include people with psychotic features to determine ketamine's safety and effectiveness.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Medicine Psychology |
| Citations | 26 |
| Key finding | The safety and efficacy of ketamine for psychotic depression are not established, and future trials should include patients with psychotic features. |
Abstract
Approximately 0.35-1% of the general population is afflicted with psychotic depression at some time in their life. Psychotic depression is a subtype of major depressive disorder characterized by mood congruent hallucinations and/or delusions. Patients with psychotic depression often represent the most severe cases, with high relapse and mortality rate. Although treatment guidelines recommend a combination of antidepressants and antipsychotics or electroconvulsive therapy, most patients subsequently relapse due to treatment resistance. Furthermore, with the concern of antipsychotic drug's side effects (e.g., tardive dyskinesia), there is a need for an alternative pharmacotherapy for psychotic depression. Recently, several case studies demonstrated that treatment with ketamine not only ameliorated mood, but also improved psychotic symptoms in patients with treatment-resistant depression and psychotic features. However, the safety of ketamine in these patients is controversial since ketamine is known to induce psychotomimetic and dissociative effects. Additionally, the efficacy and safety of ketamine in patients with psychotic depression has not been established as most clinical trials have excluded these persons due to the theorized risk of aggravating psychotic symptoms. Notwithstanding, it is not established empirically that ketamine treatment in psychotic depression would predictably amplify psychotic symptoms and/or overall illness presentation. Future trials evaluating ketamine in depression should include patients with psychotic features to inform whether ketamine is safe and effective in this subpopulation.