Atomoxetine augmentation of cholinesterase inhibitor therapy in patients with Alzheimer disease: 6-month, randomized, double-blind, placebo-controlled, parallel-trial study.
OBJECTIVE
To examine the efficacy and tolerability of atomoxetine (ATX) in improving cognitive performance of patients with Alzheimer dementia.


METHODS
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.


METHODS
Eight independent or academic outpatient clinics in the United States.


METHODS
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.


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


METHODS
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.
Mohs
Richard C
RC
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. mohsri@lilly.com
Shiovitz
Thomas M
TM
Tariot
Pierre N
PN
Porsteinsson
Anton P
AP
Baker
Kurt D
KD
Feldman
Peter D
PD
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000069445:Atomoxetine Hydrochloride; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011437:Propylamines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D018759:Adrenergic Uptake Inhibitors; D002800:Cholinesterase Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride