Placebo Effects in the Treatment of Noncognitive Symptoms of Alzheimer's Disease: Analysis of the CATIE-AD Data.

OBJECTIVE: To compare symptom trajectories between placebo and active drug responders and to examine whether early placebo improvement would be associated with subsequent placebo response in the treatment of patients with behavioral and psychological symptoms of dementia.

METHODS: A post hoc analysis of data from 371 patients with DSM-IV Alzheimer's disease in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness for Alzheimer's disease (CATIE-AD) (April 2001 to November 2004) was conducted. Patients were randomly assigned to double-blind treatment with olanzapine, quetiapine, risperidone, or placebo. Trajectories of change in Brief Psychiatric Rating Scale (BPRS) total scores were compared between placebo and active drug responders. The predictive power of improvement at week 2 for response at week 8 was investigated, and sensitivity and specificity of incremental 5% cutoff points between 5% and 25% reduction in BPRS total score at week 2 were calculated.

RESULTS: There were no significant differences in symptom trajectories between placebo and active drug responders. BPRS score reduction at week 2 was significantly associated with placebo response at week 8 (odds ratio = 1.13; P < .001). Use of a cutoff of 10% showed the highest accuracy of 0.67 (sensitivity, 0.63; specificity, 0.70).

CONCLUSIONS: Symptom trajectories of improvement of behavioral and psychological symptoms of dementia follow the same pattern irrespective of treatment. A 10% improvement at week 2 was the most appropriate predictor of subsequent placebo response at week 8, which may indicate utility for the placebo lead-in phase to minimize future trial failures of treatment for noncognitive symptoms of Alzheimer's disease.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00015548.