Effect of olanzapine on cognition during treatment of behavioral and psychiatric symptoms in patients with dementia: a post-hoc analysis.
OBJECTIVE
This study was conducted to determine the effect of olanzapine treatment on cognition in elderly patients with behavioral and psychiatric symptoms (BPSD) associated with dementia.


METHODS
This was a post-hoc analysis of three randomized double-blind, clinical trials of olanzapine (n = 682) vs placebo (n = 257) in dementia patients with BPSD in long-term or continuing-care settings. One study was 6 weeks long; the other two were 10 weeks duration, and their data were combined. Patients were subgrouped according to baseline Mini Mental State Examination (MMSE) scores: Group I = 23-26; Group II = 19-22; Group III = 14-18; Group IV = 7-13; Group V = 1-6. BPSD was assessed by the Neuropsychiatric Inventory (NPI).


RESULTS
Within-treatment group cognitive decline in patients was significant in the combined studies, but not in the 6-week study. Between-treatment cognitive changes were non-significant in the 6-week study, but showed a statistical trend in the combined studies (olanzapine, -0.78 +/- 0.19 vs placebo, -0.32 +/- 0.25; p = 0.06). In the subgroup analysis, there was a significant between-treatment difference in cognitive changes in MMSE subgroup IV in the combined studies (olanzapine, -0.63 +/- 0.26 vs placebo, 0.27 +/- 0.41, p = 0.04). Improvement in BPSD was correlated with better cognitive outcome (r = -0.2; p < 0.01).


CONCLUSIONS
Although the overall differences in cognitive changes in patients treated with olanzapine vs placebo were small and non-significant, negative effects on cognition in some patients cannot be excluded, especially in patients with more pronounced cognitive decline or whose behavioral and psychiatric symptoms are not responding to treatment.
Deberdt
Walter G
WG
Eli Lilly and Company, Brussels, Belgium. deberdt_walter@lilly.com
Siegal
Alan
A
Ahl
Jonna
J
Meyers
Adam L
AL
Landbloom
Ronald
R
D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000139:chemically induced*; D003704:Dementia / Q000523:psychology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D012920:Social Behavior Disorders / Q000188:drug therapy / Q000209:etiology
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine