Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol.
OBJECTIVE
The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis.


METHODS
Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment.


RESULTS
An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine.


CONCLUSIONS
Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.
Keefe
Richard S E
RS
Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA. richard.keefe@duke.edu
Seidman
Larry J
LJ
Christensen
Bruce K
BK
Hamer
Robert M
RM
Sharma
Tonmoy
T
Sitskoorn
Margriet M
MM
Lewine
Richard R J
RR
Yurgelun-Todd
Deborah A
DA
Gur
Ruben C
RC
Tohen
Mauricio
M
Tollefson
Gary D
GD
Sanger
Todd M
TM
Lieberman
Jeffrey A
JA
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000523:psychology; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data*; D000077152:Olanzapine; D025341:Principal Component Analysis; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D006220:Haloperidol; D000077152:Olanzapine