Olanzapine does not enhance cognition in non-agitated and non-psychotic patients with mild to moderate Alzheimer's dementia.
OBJECTIVE
This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms.


METHODS
Non-psychotic/non-agitated patients (n = 268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.5 mg/d) or placebo for 26 weeks. The primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the Alzheimer's disease Assessment Scale for Cognition (ADAS-Cog) and the Clinician's Interview-Based Impression of Change (CIBIC) after 26 weeks of therapy.


RESULTS
Patients treated with olanzapine vs placebo experienced significant worsening ADAS-Cog scores at weeks 12 (p = 0.03) and 26 (p = 0.004). Changes in CIBIC scores were not significantly different between treatment groups at either assessment. A post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (MMSE scores of 14-18) (n = 35) experienced significantly greater deterioration in ADAS-Cog performance than patients in the placebo group (n = 24; p < 0.001); whereas in patients with less cognitive impairment (n = 78, baseline MMSE scores of 23-26) between-group ADAS-Cog changes were not significant.


CONCLUSIONS
In this 26-week study non-psychotic/non-agitated patients with Alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo.
Kennedy
John
J
University of Alberta and Chinook Regional Health System, Alberta, Canada.
Deberdt
Walter
W
Siegal
Alan
A
Micca
Joseph
J
Degenhardt
Elisabeth
E
Ahl
Jonna
J
Meyers
Adam
A
Kaiser
Christopher
C
Baker
Robert W
RW
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000523:psychology*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D000077152:Olanzapine; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011595:Psychomotor Agitation; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine