Olanzapine: A new antipsychotic agent with efficacy in the management of schizophrenia

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy data, and adverse effects of olanzapine as a treatment for schizophrenia and to determine the advantages and disadvantages of this atypical antipsychotic agent compared with currently marketed agents. DATA SOURCES: A MEDLINE computer literature search was conducted to retrieve all English-language studies and review articles involving olanzapine published as of October 1, 1996. The manufacturer of the drug, Eli Lilly and Company, provided the clinical investigator's brochure and abstracts of unpublished Phase III clinical trials. STUDY SELECTION: Animal studies evaluating the pharmacology of olanzapine were evaluated, as were all open-label and double-blind studies involving the evaluation of olanzapine for the treatment of patients with schizophrenia. DATA EXTRACTION: All available clinical studies were reviewed and the interpretation of data for each study was influenced by the size of the study sample, the nature of the inclusion and exclusion criteria, and the data analysis techniques used. DATA SYNTHESIS: Olanzapine is a thienobenzodiazepine analog with an in vitro receptor affinity profile similar to that of clozapine, Olanzapine exhibits linear kinetics over the dosage range studied and is extensively metabolized in humans. Clinical evaluations to date have shown olanzapine to be at least as efficacious as typical antipsychotic agents in the treatment of the acute phase of schizophrenia. The drug was well tolerated, with significantly fewer extrapyramidal adverse effects than haloperidol. Current data suggest that olanzapine may be more effective than haloperidol for the treatment of negative symptoms; moreover, preliminary data suggest that fewer relapses occur over the course of treatment in patients treated with olanzapine compared with those taking haloperidol. CONCLUSIONS: The exact place of olanzapine in the therapy of psychotic patients remains unclear, as more data are needed to evaluate the long-term efficacy of this agent, its impact on negative symptoms, and its potential use in patients resistant to the standard agents. Despite limitations in the current database, olanzapine is a promising treatment option for patients with schizophrenia.