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, I2 = 72% on postoperative day (POD) 1; SMD-0.65, 95% CI [-1.12, -0.17], P < 0.001, I2 = 94% on POD 3; SMD-0.30, 95% CI [-0.45, -0.14], P < 0.001, I2 = 0% on POD 7; and SMD-0.25, 95% CI [-0.38, -0.11], P < 0.001, I2 = 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, I2 = 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, I2 = 30%),
headache (RR 2.47, 95% CI [1.41, 4.32], P = 0.002, I2 = 19%),
hallucination (RR 15.35, 95% CI [6.24, 37.34], P < 0.001, I2 = 89%), and
dizziness (RR 3.48, 95% CI [2.68, 4.50], P < 0.001, I2 = 89%) compared with the controls. In conclusion, perioperative application of
ketamine reduces postoperative depression and
pain scores with increased risk of adverse effects.