The effect of intravenous ketamine on depressive symptoms after surgery: A systematic review

Abstract

Study objective: The development of depressive symptoms is an important complication experienced by patients postoperatively and is associated with poor clinical outcomes. Ketamine is a feasible treatment option for depressive symptoms after surgery due to its known antidepressant effect. This meta-analysis aimed to evaluate the current body of research regarding the effects of intravenous ketamine on depressive symptoms after surgery.

Design: A meta-analysis of randomized controlled trials.

Setting: Perioperative care area.

Patients: Adult surgical patients.

Measurements: Systematic literature search was performed in the CENTRAL, MEDLINE, and EMBASE databases, for randomized controlled trials comparing the effect of intravenous ketamine versus placebo on postoperative depressive symptoms as the primary outcome, with no language restrictions. Two independent reviewers screened records for inclusion, extracted data, and assessed risk of bias. Random effects models were used to pool overall estimates. Postoperative pain intensity was also examined. The GRADE approach was used to assess the quality of evidence.

Main results: Out of 834 records screened, 9 studies met our inclusion criteria, comprising a total of 2468 patients. Compared with the control group, ketamine provided significant reduction of postoperative depression scale scores, by a standardized mean difference (SMD) of -0.89 (95% CI [-1.23, -0.73], P = 0.33, I² = 13%; 4 studies) on postoperative day (POD) 1, SMD -0.51 (95% CI [-0.99, -0.04], P < 0.001, I² = 93%; 4 studies) on POD 3, suggesting clinically relevant reduction in postoperative depressive symptoms. Postoperative depression scale scores on POD 7 were also reduced in patients receiving ketamine compared to the control group, with SMD -0.33 (95% CI [-0.52, -0.14], P = 0.36, I² = 2%; 3 studies), but the minimal clinical difference of 0.5 SMD was not reached. No significant difference was observed in the postoperative depression scale over the long term at 30 days' follow-up (SMD -0.13, 95% CI [-0.25, 0.00], P = 0.07, I² = 52%; 5 studies). A significant reduction of postoperative pain intensity on POD 1 was identified in patients following ketamine administration (SMD -1.29, 95% CI [-2.57, -0.01], P = 0.05, I² = 98%; 5 studies). However, administration of ketamine resulted in a significantly increased risk of nausea and vomiting (RR 1.71, 95% CI [1.25, 2.33], P = 0.17, I² = 35%; 6 studies), headache (RR 4.88, 95% CI [1.97, 12.06], P = 0.83, I² = 0%; 4 studies), and hallucination (RR 34.94, 95% CI [8.59, 142.17], P = 0.44, I² = 0%; 4 studies).

Conclusions: The current evidence supports intravenous ketamine administration for the treatment of depressive symptoms after surgery. While ketamine administration has clinically significant side effects, future studies are needed in surgical populations at high risk of complications.

Keywords: Ketamine; Meta-analysis; Pain; Postoperative depression.