Administration of Olanzapine to Prevent Postoperative Delirium in Elderly Joint-Replacement Patients: A Randomized, Controlled Trial

Background Delirium is a serious postoperative condition for which few pharmacologic prevention trials have been conducted. Objective The authors tested the efficacy of perioperative olanzapine administration to prevent postoperative delirium in elderly patients after jointreplacement surgery. Method The authors conducted a randomized, double-blind, placebocontrolled, prophylaxis trial at an orthopedic teaching hospital, enrolling 495 elderly patients age ≥65 years, who were undergoing elective knee- or hip-replacement surgery; 400 patients received either 5 mg of orally-disintegrating olanzapine or placebo just before and after surgery. The primary efficacy outcome was the incidence of (DSM-III-R) delirium. Results The incidence of delirium was significantly lower in the olanzapine group than in the placebo group; this held true for both knee- and hip-replacement surgery. However, delirium lasted longer and was more severe in the olanzapine group. Advanced age, a high level of medical comorbidity, an abnormal albumin level, and having knee-replacement surgery were independent risk factors for postoperative delirium (Clinicaltrials.gov Identifier: NCT000699946). Conclusion Administration of 10 mg of oral olanzapine perioperatively, versus placebo, was associated with a significantly lower incidence of delirium. These findings suggest that olanzapine prophylaxis of postoperative delirium may be an effective strategy.