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Anti-Suicidal Effects of Lithium, Ketamine, and Clozapine-A 10-Year Systematic Review.

Przemyslaw M Waszak, Jan Opalko, Natalia Olszańska, Paweł Zagożdżon

Pharmaceuticals May 18, 2025 DOI: 10.3390/ph18050742 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Sample size 49
Population Adult patients with mood disorders or schizophrenia
Interventions Lithium Clozapine Ketamine
Topics Ketamine Esketamine
Keywords Clozapine Lithium Suicidal ideation Suicidality Systematic review Suicide prevention Psychiatric medications Mental health treatments Mood stabilizers
Citations 9
Key findings Lithium, ketamine, and clozapine each reduce suicidality in their respective indicated populations, with lithium showing superiority over other mood stabilizers in bipolar disorder, ketamine providing rapid but short-lived effects, and clozapine consistently reducing suicide risk in schizophrenia.

Abstract

Background/Objectives: Suicide is a complex issue resulting in approximately 700,000 deaths annually. Individuals with mood disorders or schizophrenia are at an increased risk. Pharmacological interventions, such as lithium, clozapine, and ketamine, show promise in reducing suicidality.

Methods: A systematic search was conducted across Google Scholar, Scopus, and PubMed to identify studies evaluating the effects of lithium, clozapine, and ketamine on suicidality. Peer-reviewed articles published between 2014 and 2024 that focused on adult populations were included. After screening 1297 records, 49 studies met the eligibility criteria: 14 on lithium, 23 on ketamine, and 12 on clozapine.

Results: Multiple studies highlight lithium's significant anti-suicidal effects in patients with bipolar disorder, showing superior suicide risk reduction compared to valproate and other mood stabilizers. Ketamine has been shown to rapidly reduce suicidal ideation, with effects observable within hours and lasting up to a week. While most studies support its short-term efficacy, findings regarding its long-term benefits and the impact of repeated dosing remain inconsistent. Clozapine has consistently demonstrated a reduction in suicide risk for individuals with schizophrenia. Large-scale cohort studies report a significant decrease in suicide attempts and mortality when compared to other antipsychotics.

Conclusions: Lithium, ketamine, and clozapine were proven to be effective in reducing suicidality. However, limited data, adherence challenges, and methodological differences across studies highlight the need for more robust, large-scale experimental research. Effective suicide prevention is an extremely complex topic and also requires consideration of healthcare and social system factors.

Comparable studies

Other systematic reviews and meta-analyses on ketamine, most cited first.

Study Year Design Participants
The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline 2017 Systematic review and individual participant data meta-analysis n = 167
Ketamine use: a review Ketamine users 2011 Systematic review
Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... 2015 Systematic review and meta-analysis
Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries 2004 Systematic review n = 2,839
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review

Citations in the library

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