A current review of olanzapine's safety in the geriatric patient: from pre-clinical pharmacology to clinical data.
OBJECTIVE
Olanzapine (OLZ) is unique among currently available antipsychotic medications in its antagonism of a range of receptor systems including dopamine, norepinephrine, serotonin, acetylcholine, and histamine. Olanzapine's mechanistic complexity provides a broad efficacy profile in patients with schizophrenia and acute, pure or mixed mania. Patients experience symptomatic relief of mania, anxiety, hallucinations, delusions, and agitation/aggression and reduced depressive, negative, and some cognitive symptoms. This paper will review the safety profile of OLZ, focusing on the elderly, where data are available.


METHODS
Preclinical and clinical studies of OLZ are reviewed, with emphasis on its possible effects on the cholinergic system and the histamine H(1) receptor. Weight change and related metabolic considerations, cardiac and cardiovascular safety, and motor function during treatment with OLZ are also reviewed.


CONCLUSIONS
In vitro receptor characterization methods, when done using physiologically relevant conditions allow accurate prediction of the relatively low rate of anticholinergic-like adverse events, extrapyramidal symptoms, and cardiovascular adverse events during treatment with OLZ. Currently available clinical data suggest olanzapine is predictably safe in treating adult patients of any age with schizophrenia and acute bipolar mania, as well as in treatment of patients with some types of neurodegenerative disorders.
Kennedy
J S
JS
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Bymaster
F P
FP
Schuh
L
L
Calligaro
D O
DO
Nomikos
G
G
Felder
C C
CC
Bernauer
M
M
Kinon
B J
BJ
Baker
R W
RW
Hay
D
D
Roth
H J
HJ
Dossenbach
M
M
Kaiser
C
C
Beasley
C M
CM
Holcombe
J H
JH
Effron
M B
MB
Breier
A
A
D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009460:Neurologic Examination / Q000187:drug effects; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017981:Receptors, Neurotransmitter / Q000187:drug effects
D017981:Receptors, Neurotransmitter; D001569:Benzodiazepines; D010890:Pirenzepine; D000077152:Olanzapine