Larsen 2010.

Methods	Design: Randomised controlled trial of olanzapine to prevent postoperative delirium in elderly joint replacement patients Date of study: 2005 to 2007 Power calculation: Yes Frequency of outcomes assessment: Daily from postoperative day 1 to postoperative day 8 Inclusion criteria: All patients aged 65 years and over, patients aged less than 65 years with a history of delirium, impending joint‐replacement surgery, ability to speak English, and ability to provide informed consent Exclusion criteria: Diagnosis of dementia, active alcohol use (>10 drinks per week), a history of alcohol dependence or abuse, allergy to olanzapine, and current use of an antipsychotic medication
Participants	Number in study: 495 Country: USA Setting: Orthopaedic wards Age: Mean age 73.4 years (SD 6.1 years) in intervention group, 74.0 years (SD 6.2 years) in control group Sex: 48% female in intervention group, 60% female in control group Co‐morbidity: Not reported Dementia: Patients with dementia were excluded
Interventions	Intervention: First dose of olanzapine 5 mg (orally disintegrating tablet (ODT)) administered immediately before surgery in the pre‐anaesthesia care unit by nursing staff. Second dose of olanzapine 5 mg administered in the post‐anaesthesia care unit by nursing staff blind to the intervention arm. Control: Oral dispersible tablet placebo of similar appearance to the olanzapine tablet.
Outcomes	1. Incident delirium, measured using CAM/DSM‐III‐R 2. Severity of delirium, measured using DRS‐R‐98 3. Duration of delirium 4. Withdrawal from protocol 5. Cognition using MMSE 6. Adverse events
Notes	Funding source: New England Baptist Hospital Research Department Declarations of interest: "Theodore A Stern, has been a consultant to and is on the speaker's bureau of Eli Lilly and Company, and has been a consultant to and shareholder of WiFiMed, the company that designed the Tablet PC data‐management software. No other authors reported conflicts of interest" Delirium not excluded at enrolment
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Low risk	Randomisation sequence held in pharmacy department.  Randomisation carried out by pharmacy department.
Random sequence generation (selection bias)	Low risk	Statistician provided pharmacy with a computer‐generated random‐number table.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Hospital pharmacy prepackaged the study drug and placebo in identical packages and blinded investigators and participants.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessments conducted by research assistants and nurses and verified by a clinical psychologist. All were blind to allocation group
Incomplete outcome data (attrition bias) All outcomes	High risk	95 dropouts not included in final analysis (n = 47 in intervention, n = 48 in control). Reasons stated but imbalance between groups with loss due to anxiety, surgery cancelled and family pressure as significant factors. High rate of delirium (40% in placebo group vs 14.3% in intervention group), concern that some of the exclusions may influence outcome assessment
Selective reporting (reporting bias)	Low risk	Study protocol registered on ClinicalTrials.gov NCT000699946; outcomes reported in accordance with protocol
Other bias	Low risk	No evidence of other bias