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Am J Psychiatry 1997; 154:1248-1254
Copyright © 1997 by American Psychiatric Association
Blind, controlled, long-term study of the comparative incidence of treatment-emergent tardive dyskinesia with olanzapine or haloperidol
GD Tollefson, CM Beasley Jr, RN Tamura, PV Tran and JH Potvin
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
OBJECTIVE: Tardive dyskinesia is a serious and common complication of
neuroleptic treatment. Olanzapine is a novel antipsychotic agent exhibiting
regional mesolimbic dopaminergic selectivity and a broad- based
pharmacology encompassing serotonin, dopamine, muscarinic, and adrenergic
receptor binding affinities. The authors' goal was to compare the incidence
of tardive dyskinesia among patients receiving olanzapine and those
receiving the conventional dopamine 2 antagonist haloperidol. METHOD: Data
were analyzed from three actively controlled and blind long-term responder
studies of subjects meeting DSM-III-R criteria for schizophrenia,
schizophreniform disorder, or schizoaffective disorder treated with
olanzapine (N = 707, up to 20 mg/day, 237 median days of exposure) or
haloperidol (N = 197, up to 20 mg/day, 203 median days of exposure) who did
not have evidence of tardive dyskinesia at baseline. All of the subjects
had a chronic disease course (mean greater than 10 years), and there were
no significant between-treatment group differences in demographic or
disease characteristics. The Abnormal Involuntary Movement Scale and
research diagnostic criteria for tardive dyskinesia were used to define the
comparative incidence rates of long-term treatment-emergent tardive
dyskinesia. RESULTS: The incidence of newly emergent tardive dyskinesia at
any visit after baseline, at the final visit, and at the final two clinical
assessments was statistically significantly lower among olanzapine-treated
patients than among haloperidol-treated patients. CONCLUSIONS: These
findings support an atypical extrapyramidal symptom profile and the
potential of a significantly lower risk of tardive dyskinesia with
olanzapine than with haloperidol among patients requiring maintenance
antipsychotic treatment.
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