Atomoxetine augmentation of cholinesterase inhibitor therapy in patients with Alzheimer disease: 6-month, randomized, double-blind, placebo-controlled, parallel-trial study.

OBJECTIVES: To examine the efficacy and tolerability of atomoxetine (ATX) in improving cognitive performance of patients with Alzheimer dementia.

DESIGN: A randomized, double-blind, placebo (PLA)-controlled, parallel-groups study, starting with a 5-33-day screening and evaluation period, followed by a 6-month treatment period.

SETTING: Eight independent or academic outpatient clinics in the United States.

PARTICIPANTS: Male or female patients, aged 55 years and older, with mild-to-moderate Alzheimer disease (Mini-Mental State Examination score between 10 and 26) at baseline.

INTERVENTION: ATX (25-80 mg/day) or PLA for up to 6 months, added to ongoing cholinesterase-inhibitor therapy.

MEASUREMENTS: Alzheimer Disease Assessment Scale-Cognitive Portion (ADAS-Cog, primary measure), Clinician's Interview-Based Impression of Change score at end point, Neuropsychiatric Inventory, and Alzheimer's Disease Cooperative Study Inventory-Activities of Daily Living Inventory total score, safety measures (secondary measures).

RESULTS: Patients' (N = 92) scores on assessments of cognitive function, global clinical impression, and neuropsychiatric symptoms were not significantly different between treatment groups. Neither group showed significant changes from baseline on the primary measure of efficacy, the ADAS-Cog. The ATX group showed a significantly greater increase of heart rate, and the mean increase in diastolic blood pressure and decrease in weight differed significantly from the decrease in pressure and weight increase in the PLA group. No other clinically meaningful safety results were obtained.

CONCLUSIONS: Addition of ATX to ongoing cholinesterase-inhibitor therapy was generally well tolerated but did not significantly improve cognitive function.