Objectives: Perioperative anxiety and depression are common after major orthopaedic surgery and can impair recovery. Ketamine and esketamine have rapid psychotropic effects, but their effectiveness for postoperative mood symptoms in orthopaedic patients is uncertain. We systematically reviewed randomized evidence on these drugs for postoperative anxiety, depression, and side effects.

Methods: PubMed, Embase, and Cochrane were searched for randomized controlled trials enrolling adults undergoing major orthopaedic procedures. Eligible studies compared ketamine or esketamine administered pre-, intra-, or postoperatively with placebo or no ketamine-class drug. Primary outcomes were postoperative anxiety or depression measured using validated scales. Secondary outcomes were drug-related adverse effects.

Results: Nine randomized controlled trials were included, with follow-up ranging from 24 hours to 12 months. Five trials assessed postoperative anxiety using validated scales; four reported significantly lower anxiety scores with ketamine/esketamine at early postoperative time points, whereas one trial using a single preoperative ketamine dose reported no significant anxiolytic effect. Perioperative ketamine/esketamine may be associated with lower early postoperative anxiety and depressive symptom scores in selected orthopaedic populations. Regarding adverse effects, ketamine/esketamine did not appear to increase the incidence of common adverse events.

Conclusions: Perioperative ketamine/esketamine appears to improve early postoperative anxiety and depressive symptoms in orthopaedic patients, without increasing postoperative nausea/vomiting and dizziness. Further standardized trials are needed before firm conclusions can be drawn.

Keywords: ketamine, orthopaedic, anxiety, depression, perioperative

Level of evidence: Level II.