Effect of low-dose olanzapine on clinically relevant postoperative nausea after gynecologic laparoscopic surgery: a randomized placebo-controlled trial

Clinically relevant postoperative nausea remains common after gynecologic laparoscopic surgery despite prophylaxis. We evaluated preoperative oral olanzapine 5 mg added to routine ondansetron prophylaxis. In this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 180 adults received olanzapine 5 mg or matching placebo orally 2 h before anesthesia; all received intravenous ondansetron 8 mg. The primary outcome was nausea rated ≥ 4 on an 11-point verbal rating scale at 60 min in the post-anesthesia care unit (PACU) and at 6, 12, and 24 h. Four time-specific comparisons were assessed using two-sided Fisher’s exact tests with Holm adjustment; risk ratios (RRs) and Bonferroni-adjusted 98.75% score confidence intervals (CIs) were reported. All 180 randomized participants (90 per group) completed follow-up. At 60 min, clinically relevant nausea occurred in 2/90 (2.22%) olanzapine recipients and 9/90 (10.00%) placebo recipients (RR, 0.22; adjusted 98.75% CI, 0.04–1.20; Fisher p = 0.057; Holm-adjusted p = 0.230). No primary time point showed a statistically significant difference after adjustment. In the exploratory Apfel 3–4 subgroup, the 60-min comparison was 2/70 (2.86%) versus 8/63 (12.70%) (RR, 0.23; adjusted 98.75% CI, 0.04–1.22; Holm-adjusted p = 0.185). No oversedation was observed. Adding olanzapine 5 mg to ondansetron prophylaxis did not demonstrate a statistically significant reduction in clinically relevant postoperative nausea at the four prespecified assessments after multiplicity adjustment. The lower early-PACU event proportion is hypothesis-generating; larger trials are needed to clarify efficacy and safety. The current study was registered at https://www.thaiclinicaltrials.org/ (registration number: TCTR20221027005) (Retrospectively registered on 27 October 2022).