The central cholinergic system profile of olanzapine compared with placebo in Alzheimer's disease.
OBJECTIVE
The objective of this analysis was to compare the treatment-emergent central anticholinergic-like adverse events experienced during treatment with olanzapine versus placebo in patients with psychosis and/or agitation due to Alzheimer's disease (AD). In addition, changes in cognition were assessed in a subgroup of patients with mild to moderate cognitive impairment.


METHODS
Double-blind data were compared for placebo and three fixed olanzapine dosages (5 mg/day, 10 mg/day, and 15 mg/day) in 206 nursing home-residing patients with AD for five a priori selected central nervous system anticholinergic-like adverse events: confusion, delirium, delusions, hallucinations, abnormal thinking. Mean change from baseline to endpoint on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) was measured for a subgroup of 43 patients who had mild to moderate cognitive impairment at baseline.


RESULTS
There were no significant differences in central anticholinergic-like adverse events at any olanzapine dose compared to placebo. Additionally, in the 43-patient subgroup, there were no significant differences in mean change in ADAS-Cog scores between placebo and the three olanzapine dose subgroups.


CONCLUSIONS
Olanzapine did not differ significantly from placebo for any of the five central nervous system anticholinergic events nor on the ADAS-Cog. Olanzapine's initially reported potent in vitro muscarinic receptor affinity is not consistent with this clinical study of central nervous system anticholinergic-like adverse events in patients with AD.
Kennedy
J S
JS
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. jskennedy@LILLY.com
Zagar
A
A
Bymaster
F
F
Nomikos
G
G
Trzepacz
P T
PT
Gilmore
J A
JA
Rotelli
M D
MD
Breier
A
A
Tollefson
G
G
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects*; D002799:Cholinergic Fibers / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011976:Receptors, Muscarinic / Q000187:drug effects; D012189:Retrospective Studies
D011976:Receptors, Muscarinic; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine