A Randomized Placebo-Controlled Discontinuation Study of Cholinesterase Inhibitors in Institutionalized Patients With Moderate to Severe Alzheimer Disease.
OBJECTIVE
Cholinesterase inhibitors (ChEIs) offer modest benefits in Alzheimer disease (AD), which must be balanced against risks. Relatively few data delineate the benefits and risks of long-term ChEI administration in institutionalized patients with advanced AD. This study investigated the effects of ChEI discontinuation in institutionalized patients with AD.


METHODS
Institutionalized patients with moderate to severe AD (standardized Mini- Mental Status Examination ≤15) and treated with a ChEI for ≥2 years were randomized, double-blind, to ChEI continuation or placebo, with a 2-week tapering phase, for 8-weeks.


METHODS
The primary outcome of this pilot study was change on the Clinician's Global Impression of Change (CGI-C) scale. Secondary outcomes included safety, efficacy, and tolerability. Baseline (BL) predictors of clinical deterioration were also determined.


RESULTS
Forty patients (mean ± standard deviation age = 89.3 ± 3.5 years, standardized Mini-Mental Status Examination = 8.1 ± 5.2, Neuropsychiatric Inventory-Nursing Home version total score = 21.1 ± 15.9, 80% male) were randomized to ChEI continuation (n = 21) or placebo (n = 19). There was no significant difference in clinical worsening in the ChEI continuation (28.6%) and placebo groups (36.8%) on CGI-C (odds ratio for worsening 1.58, 95% confidence interval .38-6.55, P = .53). The occurrence of adverse events was similar in both groups. There were no significant differences in any of the secondary outcome measures. In the placebo group, BL hallucinations predicted CGI-C worsening [F(1,17) = 6.4, P = .02], and there was a trend for BL delusions to predict CGI-C worsening [F(1,15) = 3.5, P = .08].


CONCLUSIONS
These results suggest that ChEI discontinuation is safe and well tolerated in the majority of institutionalized patients with moderate to severe AD. When discontinuing ChEI, the presence of hallucinations and delusions may predict clinical deterioration, suggesting the need for increased caution.
Geriatric Psychiatry, Sunnybrook Health Sciences Center, Toronto, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Psychiatry, North York General Hospital, Toronto, Canada.
Nathan
N
Herrmann
Department of Psychiatry, University of Toronto, Toronto, Canada.
Jordana
J
O'Regan
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
Myuri
M
Ruthirakuhan
Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada.
Alexander
A
Kiss
Psychiatry, North York General Hospital, Toronto, Canada.
Goran
G
Eryavec
Long-Term Care, Sunnybrook Health Sciences Center, Toronto, Canada.
Evelyn
E
Williams
Geriatric Psychiatry, Sunnybrook Health Sciences Center, Toronto, Canada; Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada. Electronic address: krista.lanctot@sunnybrook.ca.
Krista L
KL
Lanctôt
D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009735:Nursing Homes; D010865:Pilot Projects; D012720:Severity of Illness Index
D002800:Cholinesterase Inhibitors
Alzheimer disease; Cholinesterase inhibitors; institutionalization; neuropsychiatric symptoms; randomized controlled trial