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Academic Highlights

Effect of Second-Generation Antipsychotics on Caregiver Burden in Alzheimer’s Disease

Somaia Mohamed, MD, PhD; Robert Rosenheck, MD; Constantine G. Lyketsos, MD, MHS; Richard Kaczynski, PhD; David L. Sultzer, MD; and Lon S. Schneider, MD

Published: September 6, 2011

Article Abstract

Background: Alzheimer’s disease (AD) imposes a severe burden upon patients and their caregivers. Severity of psychiatric symptoms and behavioral disturbances is an important determinant of caregivers’ experience of burden. These symptoms may be improved with atypical antipsychotic treatment.

Objective: Data from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer’s Disease (CATIE-AD) trial were used to evaluate the effect of atypical antipsychotics versus placebo on the experiences of caregivers of outpatients with AD.

Method: We compared the effect of atypical antipsychotic drugs (olanzapine, risperidone, or quetiapine—considered together as a group) versus placebo on the experiences of caregivers of AD outpatients (diagnosed according to DSM-IV-TR). We also evaluated whether improvement in patients’ psychiatric and behavioral symptoms mediated the relationship between drug treatment and caregiver burden. The CATIE-AD trial, conducted from April 2001 through November 2004, included outpatients (mean age = 77.9 years [SD = 7.5 years]) in usual care settings and assessed treatment effectiveness over a 9-month period at 42 US sites. In a set of secondary analyses, data from CATIE-AD participants who had at least 1 postbaseline outcome assessment and data from their caregivers were examined in an intention-to-treat (ITT) analysis (N = 361). A phase 1-only analysis was conducted including only observations while patients were receiving the initially randomized drug (N = 153). The Burden Interview, the Beck Depression Inventory, and the Neuropsychiatric Inventory (NPI) Caregiver Distress Scale were used to evaluate caregiver burden.

Results: In both ITT and phase 1-only analyses, caregivers of patients treated with second-generation antipsychotics scored significantly lower than caregivers of patients receiving placebo on both the Burden Interview (P = .0090) and the NPI Caregiver Distress Scale (P = .0209). These differences appeared to have been mediated by lower levels of agitation, hostility, and psychotic distortions.

Conclusion: In AD patients with symptoms of psychosis, agitation, or aggressive behavior, medications can have a small but significant impact on caregiver burden.

J Clin Psychiatry 2012; 73(1):’ ‹121-128

Submitted: September 12, 2010; accepted February 18, 2011.

Online ahead of print: September 6, 2011 (doi:10.4088/JCP.10m06574).

Corresponding author: Somaia Mohamed, MD, PhD, Veterans Affairs Connecticut Health Care System, 950 Campbell Ave, #182, West Haven, CT 06516 (

Volume: 72

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