Introduction. Since a variety of comparisons between risperidone and olanzapine have resulted in diverse outcomes, so safety and efficacy of them were compared again in a new trial. Method. Sixty female schizophrenic patients entered into one of the assigned groups for random allocation to olanzapine or risperidone ( in each group) in a double-blind, 12-week clinical trial. Scale for Assessment of Positive Symptoms (SAPS) and Scale for Assessment of Negative Symptoms (SANS) were used as the primary outcome measures. Clinical Global Impressions-Severity Scale (CGI-S), Schedule for Assessment of Insight (SAI), and finally Simpson Angus Scale (SAS) as well were employed as secondary scales. Results. While both of olanzapine and risperidone were significantly effective for improvement of positive symptoms ( ), as regards negative symptoms, it was so only by means of olanzapine ( ). CGI-S and SAI, as well, were significantly improved in both of the groups. SAS increment was significant only in the risperidone group ( ). Conclusion. While both of olanzapine and risperidone were equally effective for improvement of positive symptoms and insight, olanzapine showed superior efficacy with respect to negative symptoms, along with lesser extrapyramidal side effects, in comparison with risperidone. 1. Introduction Schizophrenia is characterized by its chronic recurring course . In addition, as many as 30–40% of such patients may exhibit an insufficient or poor response to conventional antipsychotics  and up to 50% of them may experience serious side effects by such treatments . So the focus of new drug development for treatment of schizophrenia has shifted to synthesize compounds capable of alleviating negative symptoms, which are commonly unresponsive to classical antipsychotics, and to synthesize compounds less likely to produce extrapyramidal side effects. At the beginning, atypical antipsychotics seemed to be more efficient than conventional antipsychotics, but in a meta-analysis for comparing the effects of first-generation antipsychotics with second-generation ones, the latter cluster was found to be no more efficacious than the first-generation drugs in schizophrenic patients, even with respect to negative symptoms . Olanzapine is a thienobenzodiazepine with a high affinity for serotonin 5-HT2, histamine H1, α1-adrenergic, D1, and D2 dopamine receptors . Controlled clinical trials have shown that it has better efficacy and healthier side-effect profile than haloperidol and according to some studies seems to be more efficient in the management
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