European journal of clinical pharmacologyDec 20, 2023

Effects of Ketamine and Esketamine on Suicidal Thoughts in Hard-to-Treat Depression: A Review and Analysis

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 27, 2026

Abstract

A total of 391 patients with treatment-resistant depression were analyzed in five randomized clinical trials assessing ketamine and esketamine.

No statistically significant reduction in suicidal ideation was observed with ketamine or esketamine compared to placebo.
The standardized mean difference for suicidal ideation was -0.66, indicating no meaningful effect.
Antidepressant effects also showed no significant difference, with a standardized mean difference of -0.99.
These findings suggest that ketamine and esketamine may not effectively reduce suicidal thoughts in this patient population.
Further studies are needed to confirm these results and explore potential effects.

Simplified

PURPOSE: To systematically assess the evidence of efficacy and safety of the use of ketamine and esketamine for patients with treatment-resistant depression (TRD) with suicidal ideation (SI).

METHODS: We independently searched for clinical trials from inception to January 2023 using electronic databases, e.g., PubMed and EMBASE. A systematic review and meta-analysis were performed to assess SI scores of depression rating scales, which were regarded as the outcomes.

RESULTS: A total of five independent double-blind, placebo controlled randomized clinical trials (RCTs) are eligible for inclusion. Four of the studies used ketamine as an intervention and one used esketamine as an intervention. Three hundred ninety-one patients with TRD were included (the intervention group with ketamine or esketamine is 246, and the control group is 145). No statistically significant interaction between the subscales of suicide ideation (SMD = - 0.66, 95% CI (- 1.61, 0.29); Z = 1.36, P = 0.17) and antidepressant effects (SMD = - 0.99, 95% CI (- 2.33, 0.34); Z = 1.46, P = 0.15) based on the results of ketamine and esketamine, compared with placebo groups.

CONCLUSION: This meta-analysis suggested that esketamine and ketamine have failed to reduce suicidal ideation in patients with TRD. Further studies are desirable to confirm the effects of ketamine and esketamine in TRD patients.

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Effects of Ketamine and Esketamine on Suicidal Thoughts in Hard-to-Treat Depression: A Review and Analysis

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