Quetiapine treatment of psychosis associated with dementia: a double-blind, randomized, placebo-controlled clinical trial.
OBJECTIVE
The objectives of this study were to evaluate the efficacy, safety, and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning.


METHODS
The authors conducted a multicenter, double-blind, placebo-controlled, randomized trial of flexibly dosed quetiapine and haloperidol. Primary outcomes were change in total Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions-Severity of Illness (CGI-S) scores at week 10. Secondary outcomes included BPRS factors, Neuropsychiatric Inventory (NPI), Multidimensional Observation Scale for Elderly Subjects (MOSES), and Physical Self-Maintenance Scale (PSMS).


RESULTS
Two hundred eighty-four participants (mean age: 83.2 years) were randomized; 63.4% completed; and mean Mini-Mental State Examination score was 12.8. Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol. No differential benefit was seen on any psychosis measure. BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol. BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo. No NPI factors showed change, including the agitation factor. MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine. Somnolence occurred in 25.3%, 36.2%, and 4.1% of the quetiapine, haloperidol, and placebo groups, respectively; parkinsonism was most prevalent in the haloperidol group; other safety and tolerability measures differed little among groups.


CONCLUSIONS
All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed. Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation. Tolerability was better with quetiapine compared with haloperidol.
Tariot
Pierre N
PN
Memory Disorders Center, Banner Alzheimer's Disease Institute, Phoenix, Arizona, USA. pierre.tariot@bannerhealth.com
Schneider
Lon
L
Katz
Ira R
IR
Mintzer
Jacobo E
JE
Street
Jamie
J
Copenhaver
Margaret
M
Williams-Hughes
Celeste
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000517:prevention & control; D001921:Brain / Q000503:physiopathology; D010054:Brief Psychiatric Rating Scale; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D039721:Diagnostic and Statistical Manual of Mental Disorders; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006220:Haloperidol / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011595:Psychomotor Agitation / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology*; D000069348:Quetiapine Fumarate; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000209:etiology
D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D006220:Haloperidol