Efficacy of Ondansetron in the Prevention or Treatment of Post-operative Delirium—a Systematic Review

Background Post-operative delirium (POD) is associated with higher rates of functional decline and death. Ondansetron is a serotonin antagonist which could represent a therapeutic or preventive option in POD. Methods A systematic review of MEDLINE, EMBASE, CENTRAL, and PsychINFO was performed. Three randomized controlled trials (RCTs) met inclusion criteria (intervention of ondansetron compared to a control group). Results Two RCTs examined ondansetron for the treatment of POD in patients after cardiac or post-trauma surgery in the ICU. Studies assessed either a one-time dose or doses for 3 days of ondansetron or haloperidol IV. They suggested similar reductions in average delirium scores and rates in both interventions, although one study suggested ondansetron to be associated with higher rates of rescue haloperidol use. One RCT examined prophylactic ondansetron versus placebo IV, for five days postoperatively, to prevent POD in orthopedic patients. There were significantly fewer delirious patients in the ondansetron group. In general, studies had major methodological limitations and were very heterogenous in study tools, interventions used, and populations studied. Conclusions Ondansetron may be an effective agent for the prevention or treatment of POD, but studies are few and of poor quality, thus making the conclusions tenuous. Further large RCTs are needed.