Perioperative Ketamine and Esketamine for Postoperative Mood Symptoms After Orthopaedic Surgery: A Systematic Review of Randomized Controlled Trials.
Ali Dabbagh, Firoozeh Madadi, Maryam Fallah, Negarsadat Namazi
The archives of bone and joint surgery 2026 DOI: 10.22038/abjs.2026.94686.4270 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Population | Adults undergoing major orthopaedic procedures |
| Interventions | Ketamine Esketamine |
| Duration | Follow-up durations ranging from 24 hours to 12 months |
| Topics | Anxiety Depression Ketamine Esketamine |
| Keywords | Orthopaedic Perioperative |
| Key findings | Across nine randomized trials, perioperative ketamine or esketamine may be associated with lower early postoperative anxiety and depressive symptom scores in selected orthopaedic patients; four of five trials assessing anxiety with validated scales found significantly lower early anxiety scores, while one trial of a single preoperative ketamine dose found no significant anxiolytic effect. The agents did not appear to increase common adverse events. |
Abstract
Perioperative anxiety and depression are common following major orthopaedic surgery and may adversely affect postoperative recovery. Ketamine and esketamine have rapid psychotropic effects; however, their effectiveness in reducing postoperative mood symptoms in orthopaedic patients remains uncertain. We systematically reviewed randomized evidence on the effects of these agents on postoperative anxiety, depression, and adverse events. PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials enrolling adults undergoing major orthopaedic procedures. Eligible studies compared ketamine or esketamine administered preoperatively, intraoperatively, or postoperatively with placebo or no ketamine-class agent. The primary outcomes were postoperative anxiety and depression assessed using validated scales. Secondary outcomes included drug-related adverse events. Nine randomized controlled trials were included, with follow-up durations ranging from 24 hours to 12 months. Five trials assessed postoperative anxiety using validated scales; four reported significantly lower anxiety scores with ketamine or esketamine at early postoperative time points, whereas one trial using a single preoperative dose of ketamine found no significant anxiolytic effect. Overall, perioperative ketamine or esketamine may be associated with lower early postoperative anxiety and depressive symptom scores in selected orthopaedic populations. Regarding safety, ketamine or esketamine did not appear to increase the incidence of common adverse events. Perioperative ketamine or esketamine appears to reduce early postoperative anxiety and depressive symptoms in orthopaedic patients without increasing postoperative nausea, vomiting, or dizziness. Further standardized trials are needed before firm conclusions can be drawn. II.
Comparable studies
Other systematic reviews and meta-analyses on esketamine for anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review. Youth ≤19 years old with mood disorders, anxiety, or suicidality | 2025 | Systematic review | |
| Ketamine-induced altered states of consciousness: a systematic review of implications for therapeutic outcomes in psychiatric practices. Patients with mood disorders (major depressive disorder, bipolar disorder), substance... | 2024 | Systematic review | n = 29 |
| Evaluating the potential risk of ketamine-induced hepatotoxicity in the treatment of mood and anxiety disorders: A systematic review. Patients with mood, anxiety, or related psychiatric disorders receiving therapeutic... | 2026 | Systematic review | n = 1,017 |
| Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: Systematic review. Patients with DSM-5 anxiety disorders or unipolar/bipolar treatment-resistant depression | 2026 | Systematic review |