Citation

Tollefson GD, Taylor CC. CNS Drug Rev. 2000; 6(4): 303-363.

Copyright

(Copyright © 2000, Neva Press, Inc)

DOI

10.1111/j.1527-3458.2000.tb00155.x

PMID

unavailable

Abstract

The novel antipsychotic agent olanzapine (Zyprexa®, Eli Lilly and Company) is a thienobenzodiazepine analog marketed for the treatment of schizophrenia. Olanzapine's diverse receptor binding profile and greater affinity for serotonin receptors over dopamine receptors is thought to impart antipsychotic efficacy with a low incidence of serious extra-pyramidal symptoms (EPS). With once daily dosing steady-state plasma concentrations reached within approximately 1 week. Olanzapine is extensively metabolized by the liver, is mostly excreted in the urine, and has few drug intractions. In clinical trials, the efficacy of olanzapine for treating schizophrenia is better than placebo and haloperidol and comparable to risperidone. Olanzapine may also ameliorate some comorbid symptoms including negative symptoms, depression, anxiety, substance abuse, and cognitive dysfunction, and it is effective in the long-term maintenance of response, treatment-resistance, and improving quality of life. The overall direct costs are lower with olanzapine treatment compared with haloperidol or risperidone treatment. In clinical trials, olanzapine demonstrates a favorable safety profile. The most frequently reported treatment-emergent adverse events are somnolence, schizophrenic reaction, insomnia, headache, agitation, rhinitis, and weight gain. Significantly fewer EPS (based on formal rating scales) and incidences of tardive dyskinesia have been reported for olanzapine compared with haloperidol. Olanzapine has not been associated with persistent elevations of prolactin above the upper limit of normal nor has it been associated with clinically significant changes in cardiac QTc interval. Fewer incidences of suicide attempts have been reported with olanzapine compared with placebo, haloperidol, or risperidone treatments. There is evidence that olanzapine may be effective in the treatment of mood disorders, psychosis associated with Alzheimer's disease, obsessive-compulsive disorder, pervasive developmental disorders, and delirium. Patients with schizophrenia have been successfully switched from other antipsychotics to olanzapine. In conclusion, olanzapine offers a significantly improved risk-to-benefit profile compared with haloperidol and possible risperidone, and thus should be considered an important treatment option for schizophrenia and related disorders.

Language: en

Keywords

Antipsychotic agent; benzodiazepine derivative; carbamazepine; clinical trial; clozapine; comorbidity; controlled clinical trial; controlled study; disease association; Dopamine antagonist; dopamine receptor; double blind procedure; drug blood level; drug cost; drug efficacy; drug metabolism; drug receptor binding; drug safety; extrapyramidal symptom; haloperidol; human; insomnia; long term care; meta analysis; neuroleptic agent; nonhuman; olanzapine; Olanzapine; placebo; prolactin; prolactin blood level; QT interval; quality of life; randomized controlled trial; receptor affinity; review; risk benefit analysis; risperidone; schizophrenia; Schizophrenia; Serotonin antagonist; serotonin receptor; somnolence; suicide attempt; tardive dyskinesia