Abstract
ABSTRACTThe 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 extrapyramidal 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 possibly risperidone, and thus should be considered an important treatment option for schizophrenia and related disorders.SUMMARYOlanzapine is an innovative pharmaceutical product that has been prescribed to more than four million individuals worldwide. Olanzapine has a diverse neurotransmitter receptor binding profile that is similar to clozapine, with selective affinity for the serotonin receptors over the dopamine receptors. In vitro and in vivo preclinical experimentation has provided evidence for the antipsychotic efficacy of olanzapine with a low incidence of serious EPS. In addition, olanzapine has a pharmacokinetic profile that allows for single daily dosing and has minimal metabolic interactions with commonly coadministered medications. Through its distinct pharmacology, olanzapine offers patients a significantly improved risk‐benefit profile.Across the diverse series of clinical studies discussed in this review, olanzapine has helped to redefine the expectations for the pharmacotherapy of schizophrenia. Olanzapine (5 to 20 mg/day) has demonstrated an improvement in total psychopathology, which was significantly greater than that seen with placebo or the active comparator, haloperidol. This effect was comprised of at least comparable benefits to haloperidol on positive psychotic symptoms and superior results for the more chronic and disabling features of negative, concurrent anxious and depressive, and cognitive symptoms. This broadened range of treatment‐responsive symptoms is complemented by a greater depth of clinical response as well. Given the historical challenge of compliance with the older antipsychotic drugs, it is also noteworthy that these outcomes were achieved with an adverse event discontinuation rate similar to placebo. Compared with conventional antipsychotic agents, the incidence of troublesome EPS or hyperprolactinemia was low. Studies in special populations (i.e., the geriatric patient) appear to confirm this safety profile.Because schizophrenia is a chronic disease, controlled and blinded maintenance studies showing the superiority of olanzapine to placebo or active comparators (haloperidol, risperidone) are also reassuring, especially in the context of the long‐term safety experience with olanzapine. In particular, data suggesting a lower incidence of potentially irreversible movement disorders, such as tardive dyskinesia, are striking and of importance to treatment decision makers. Moreover, these advantages appear to translate into improved quality of patient life, increased functional well‐being (i.e., return to work), and an overall reduction in the total direct cost of managing schizophrenia.While further studies are ongoing, the data on olanzapine in mood disorders and psychosis associated with Alzheimer's disease are encouraging. Additional studies evaluating olanzapine in nonschizophrenic disorders are awaited. As more “atypical” agents enter the marketplace, head‐to‐head comparisons are encouraged to properly evaluate the relative merits of each compound. Experience to date tells us that the newer agents to treat psychosis are not all alike. Based on the clinical review in this paper, olanzapine does seem to represent a novel and compelling first‐line option for the management of psychotic disorders.
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