Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial.
OBJECTIVE
This international, multicenter double-blind trial was designed to compare the therapeutic profile of an atypical antipsychotic, olanzapine, with that of a conventional dopamine D2 antagonist, haloperidol.


METHODS
A total of 1,996 patients at 174 sites in Europe and North America were randomly assigned to treatment with olanzapine (N = 1,336) or haloperidol (N = 660) over 6 weeks. The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale (BPRS). Secondary analyses included comparisons of the mean change in positive and negative symptoms, comorbid depression, extrapyramidal symptoms, and overall drug safety.


RESULTS
Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure, including depression. Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events. Substantially more olanzapine-treated patients (66.5%) than haloperidol-treated patients (46.8%) completed 6 weeks of therapy. Statistically significant advantages of olanzapine treatment were related to 1) change in negative symptoms, 2) extrapyramidal symptom profile, 3) effect on prolactin levels, and 4) response rate.


CONCLUSIONS
Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology, with a substantially more favorable safety profile, than haloperidol. It meets several of the criteria for a novel atypical antipsychotic agent.
Tollefson
G D
GD
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Beasley
C M
CM
Tran
P V
PV
Street
J S
JS
Krueger
J A
JA
Tamura
R N
RN
Graffeo
K A
KA
Thieme
M E
ME
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000453:epidemiology; D001569:Benzodiazepines; D015897:Comorbidity; D003866:Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009656:North America; D000077152:Olanzapine; D010352:Patient Dropouts; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine