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A systematic review and meta-analysis of the efficacy of ketamine and esketamine on suicidal ideation in treatment-resistant depression

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Abstract

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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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Ads:

Antidepressants

CI:

Confidence

MADRS-SI:

Montgomery-Åsberg Depression Rating Scale suicidality item

CRSS-SI:

Columbia Suicide Severity Rating Scale suicidality item

CSSRS:

Columbia Suicide Severity Rating Scale

DB:

Double-blind

DSM-5:

Diagnostic and Statistical Manual of Mental Disorders (fifth edition) criteria

HAM-D:

Hamilton Depression Rating Scale

IN:

Intranasal

IV:

Intravenous injection

MADRS:

Montgomery-Åsberg Depression Rating Scale

MDD:

Major depressive disorder

RCTs:

Randomized clinical trials

SCID:

Structured Clinical Interview for DSM-IV Diagnoses

SI:

Suicidality item

SIcomposite :

A composite explicit suicidality index (Beck Scale, MADRS, and Quick Inventory of Depressive Symptomatology-Self Report)

TRD:

Treatment-resistant depression

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 82274127 and 82104644).

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Authors and Affiliations

  1. Department of Anatomy, School of Chinese Medicine, Beijing University of Chinese Medicine, Sunshine Southern Avenue, Fang-Shan District, Beijing, 102488, China

    Ya-Ting Wang, Xiao-Le Wang, Lan Lei, Zhen-Yu Guo, Fei-Fei Kan, Die Hu, Cong Gai & Yi Zhang

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Contributions

Y-TW: investigation, methodology, formal analysis, writing—original draft. X-LW: investigation, methodology, formal analysis. LL: investigation. Z-YG: investigation. F-FK: investigation. DH: investigation. CG: investigation. YZ: conceptualization, methodology, supervision, writing—review and editing. All the authors read and approved the final manuscript.

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Correspondence to Yi Zhang.

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Wang, YT., Wang, XL., Lei, L. et al. A systematic review and meta-analysis of the efficacy of ketamine and esketamine on suicidal ideation in treatment-resistant depression. Eur J Clin Pharmacol 80, 287–296 (2024). https://doi.org/10.1007/s00228-023-03605-1

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