Olanzapine, quetiapine, or risperidone did not differ from placebo for Alzheimer disease.

M e t h o d s Design: Randomized placebo-controlled trial (Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer’s Disease ). Allocation: Concealed.* Blinding: Blinded (clinicians and patients).* Follow-up period: Up to 36 weeks. Setting: 42 sites in the United States. Patients: 421 outpatients (mean age 78 y, 56% women) who had AD or probable AD. All patients had had psychosis, aggression, or agitation almost daily during the previous week or at least intermittently for 4 weeks. Exclusion criteria were a primary psychotic disorder, delirium, or other dementia; psychosis, aggression, or agitation better accounted for by another medical condition or medication or by substance abuse; psychiatric admission; suicidal trend; treatment with a cholinesterase inhibitor or antidepressant; previous treatment with ≥ 2 of 3 study drugs; or contraindications to any of the study drugs. Intervention: Olanzapine, 2.5 or 5.0 mg daily (n = 100); quetiapine, 25 or 50 mg daily (n = 94); risperidone, 0.5 or 1.0 mg daily (n = 85); or placebo (n = 142). The study physicians determined the starting doses and adjusted the doses based on clinical judgment and patients’ responses. A benzodiazepine or haloperidol could also be prescribed. Outcomes: Time to discontinuation of treatment for any reason. Secondary outcomes included attainment of minimal or greater improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks; time to discontinuation of treatment because of lack of efficacy; time to discontinuation of treatment because of adverse events, intolerability, or death; and adverse events. Patient follow-up: 98.8% (intention-to-treat analysis).