Early Improvements of Individual Symptoms With Antipsychotics Predict Subsequent Treatment Response of Neuropsychiatric Symptoms in Alzheimer's Disease: A Re-Analysis of the CATIE-AD Study.

OBJECTIVE

The aim of the present study was to identify individual symptoms whose early improvements contributed to subsequent treatment response to antipsychotics for neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) using the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD).

METHODS

The CATIE-AD study was conducted between April 2001 and November 2004 at 45 sites in the United States. Data for 421 patients with DSM-IV AD with NPSs treated with antipsychotics were analyzed in the present study. Treatment response was defined as a reduction of ≥ 9 points in the Neuropsychiatric Inventory (NPI) score or a reduction of ≥ 25% from baseline in Brief Psychiatric Rating Scale (BPRS) total score at week 8. Logistic regression analyses were performed to examine associations between response and clinical and demographic characteristics, including each total or individual symptom score reduction at week 2.

RESULTS

Reduction in NPI or BPRS total score at week 2 and several individual symptom score reductions (euphoria/elation, irritability, hallucinations, anxiety, agitation, apathy, disinhibition, and depression among NPI subitems; excitement, suspiciousness, disorientation, hostility, depressive mood, and emotional withdrawal among BPRS subitems) at week 2 were significantly associated with subsequent treatment response at week 8 (all P values < .05); Early non-improvements of irritability and suspiciousness were shown to be especially influential clinical markers in predicting subsequent treatment nonresponse. Furthermore, healthier condition at baseline was significantly associated with treatment response at week 8 (P < .05).

CONCLUSIONS

Although further research to validate these preliminary findings is needed, focusing on early improvements of individual symptoms could help identify subsequent treatment responders to antipsychotics in AD patients with NPSs.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00015548.