Esketamine and Perioperative Anxiety: Meta-Analysis Findings

Key Takeaways

• Esketamine was associated with lower perioperative anxiety than control across the pooled randomized evidence in anesthetized adults.
• Between-study heterogeneity was substantial, and subgroup analyses did not show measurable benefit in adults younger than 40 years, abdominal operations, or spinal anesthesia.
• No statistically significant differences were reported for sleep parameters, pain relief, surgical or anesthetic duration, intraoperative metrics, or adverse-event rates, and the authors concluded that further high-quality trials are needed.

Across eight randomized trials involving 1,101 anesthetized adults, esketamine was linked to lower perioperative anxiety than control interventions in a PubMed-indexed systematic review and meta-analysis. The trials spanned adults undergoing anesthesia for different surgical procedures, maintaining a perioperative focus across a broader operative population. Randomized comparisons of esketamine versus control centered on perioperative anxiety, and the pooled analysis showed a modest overall reduction in anxiety. Broader perioperative outcomes were neutral, and adverse-event rates did not differ significantly from control groups.

The analysis pooled randomized controlled trials in anesthetized adults comparing esketamine with control interventions for perioperative anxiety-related outcomes. Searches covered PubMed, Embase, the Cochrane Library, and Web of Science, and the investigators used Review Manager 5.4 and Stata for the quantitative analyses. Included studies needed sufficient perioperative data for meta-analysis, limiting the dataset to trials that supported pooled estimates. Primary outcomes were changes in anxiety and depression scores, while sleep and pain scores plus perioperative data were secondary outcomes. The review centered on anxiety while also examining several related perioperative measures.

In the pooled comparison, esketamine was associated with lower perioperative anxiety, with a standardized mean difference of -0.36 and a 95% confidence interval from -0.67 to -0.06. The reported p value was less than 0.0001, and heterogeneity was high at I² = 84%. Sensitivity analyses suggested that anxiety findings varied across the included trials, whereas depression findings remained consistent. Overall, the pooled results favored esketamine for anxiety, but the signal varied across settings.

Subgroup analyses did not show measurable benefit among adults younger than 40 years, among patients undergoing abdominal operations, or among those receiving spinal anesthesia. Secondary outcomes also remained neutral across the pooled evidence. No statistically significant improvements were reported for sleep parameters, pain relief, surgical duration, anesthetic duration, or intraoperative measures such as fluid administration, blood loss, and urine output. The pattern pointed to a narrower anxiety signal rather than a universal perioperative effect.

Pooled adverse-event rates did not differ significantly between esketamine and control groups in the included trials. The investigators concluded that further high-quality trials are needed to clarify dosing regimens, delivery methods, and combination strategies aimed at improving efficacy and reducing side effects. The current evidence was suggestive, but not fully settled.