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Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies

Jie Guo, Di Qiu, Han-Wen Gu, Xing-Ming Wang, Kenji Hashimoto, Guang-Fen Zhang, Jian-Jun Yang

Molecular Psychiatry January 20, 2023 DOI: 10.1038/s41380-023-01945-z (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Meta-analysis Randomized Peer reviewed
Sample size 3,159
Population Patients undergoing surgery
Intervention Ketamine
Topics Depression Esketamine Ketamine
Citations 46
Key findings Perioperative ketamine reduces postoperative depression scores and pain scores on day one but increases the risk of nausea, vomiting, headache, hallucination, and dizziness.

Abstract

Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy and safety of the perioperative application of ketamine on postoperative depression remains uncertain. We performed a meta-analysis to determine the effect of perioperative intravenous administration of ketamine on postoperative depression. Randomized controlled trials comparing ketamine with placebo in patients were included. Primary outcome was postoperative depression scores. Secondary outcomes included postoperative visual analog scale (VAS) scores for pain and adverse effects associated with ketamine. Fifteen studies with 1697 patients receiving ketamine and 1462 controls were enrolled. Compared with the controls, the ketamine group showed a reduction in postoperative depression scores, by a standardized mean difference (SMD) of −0.97, 95% confidence interval [CI, −1.27, −0.66], P < 0.001, I^2 = 72% on postoperative day (POD) 1; SMD−0.65, 95% CI [−1.12, −0.17], P < 0.001, I^2 = 94% on POD 3; SMD−0.30, 95% CI [−0.45, −0.14], P < 0.001, I^2 = 0% on P OD 7; and SMD−0.25, 95% CI [−0.38, −0.11], P < 0.001, I^2 = 59% over the long term. Ketamine reduced VAS pain scores on POD 1 (SMD−0.93, 95% CI [−1.58, −0.29], P = 0.005, I^2 = 97%), but no significant difference was found between the two groups on PODs 3 and 7 or over the long term. However, ketamine administration distinctly increased the risk of adverse effects, including nausea and vomiting (risk ratio [RR] 1.40, 95% CI [1.12, 1.75], P = 0.003, I^2 = 30%), headache (RR 2.47, 95% CI [1.41, 4.32], P = 0.002, I^2 = 19%), hallucination (RR 15.35, 95% CI [6.^24, 37.34], P < 0.001, I^2 = 89%), and dizziness (RR 3.48, 95% CI [2.68, 4.50], P < 0.001, I^2 = 89%) compared with the controls. In conclusion, perioperative application of ketamine reduces postoperative depression and pain scores with increased risk of adverse effects.

Comparable studies

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

Study Year Design Participants
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
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

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