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Objective: To compare the clinical and economic outcomes associated with olanzapine and risperidone treatment for schizophrenia., Design and Setting: An international, multicentre, double-blind, prospective study. To facilitate economic comparisons, our sample was restricted to patients enrolled in US sites. 150 patients with a Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV) diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder were randomised to therapy with either olanzapine 10 to 20 mg/day (n = 75) or risperidone 4 to 12 mg/day (n = 75) for a maximum of 28 weeks. In addition to tolerability and efficacy assessments, use of health services was assessed at baseline and prospectively, at 8-week intervals and at study completion. Clinically important response, defined as a 40% improvement in the Positive and Negative Syndrome Scale total score, maintenance of response and rates of treatment-emergent extrapyramidal symptoms were compared between groups. Direct medical costs were estimated by assigning standardised prices to resource units. Median total, inpatient/outpatient service and medication acquisition costs were compared between treatment groups., Main Outcome Measures and Results: The mean modal dosages for the olanzapine and risperidone treatment groups were 17.7 +/- 3.4 mg/day and 7.9 +/- 3.2 mg/day, respectively. Olanzapine-treated patients were more likely to maintain response compared with risperidone-treated patients (p = 0.048). In addition, a smaller proportion of olanzapine-treated patients required anticholinergic therapy compared with risperidone-treated patients (25.3 vs 45.3%; p = 0.016). Total per patient medical costs over the study interval were $US2843 (1997 values) [36%] lower in the olanzapine treatment group than in the risperidone treatment group (p = 0.342). Medication costs were significantly higher for olanzapine-treated patients ($US2513 vs $US1581; p < 0.001), but this difference was offset by a reduction of $US3774 (52%) in inpatient/outpatient service costs for olanzapine-treated patients in comparison with risperidone-treated patients ($US3516 vs $US7291, p = 0.083). Median cost findings were consistent with results observed using other robust measures of central tendency and provide conservative estimates of potential savings that may be obtained from olanzapine therapy., Conclusions: In this study, olanzapine-treated patients experienced clinical improvements that translated into savings in costs of care for both inpatient and outpatient services. These savings offset the difference in medication acquisition cost between olanzapine and risperidone.

Background: Depressive symptoms are common during the course of schizophrenia and may carry prognostic relevance., Methods: From a 28-week prospective, double-blind, randomized study of olanzapine and risperidone, a post hoc evaluation of changes on the Positive and Negative Syndrome Scale (PANSS) depression cluster (PDC) and the subsequent risk of relapse were analyzed by logistic regression., Results: Olanzapine was associated with a significantly higher categorical rate of improvement on the PANSS depression cluster (> or = 7 points) (p < .05). Although the baseline severity of depressive symptoms was not a significant predictor of relapse, the degree of acute (8-week) mood improvement on the PANSS depression cluster (but neither negative or positive symptom changes) was related to the probability of a subsequent psychotic relapse. Acute mood improvement with olanzapine was inversely related to a nonsignificantly lower risk of relapse. However, an opposite and significant relationship was observed among risperidone-treated subjects. Risperidone-treated subjects with a greater degree of acute mood change were both 3.58 times more likely to relapse than their risperidone counterparts who had experienced less mood improvement (p = .008) and 8.55 times more likely than olanzapine-treated subjects who had had similar mood improvements (p = .001)., Conclusions: These data suggest the underlying pharmacologic differences between the two drugs may bestow different rates of longer-term mood stabilization and relapse prevention. In a second series of analyses, worsening on the PANSS depression cluster in the 4 weeks or less preceding a clinical relapse was a significant prodromal predictor of relapse among all subjects. As a whole, subjects with a worsening on the PDC demonstrated a 1.77 times higher risk of a relapse during the subsequent 4 weeks (p = .001). Among this mood-worsening stratum, risperidone-treated patients were 3.51 times more likely to relapse in those next 4 weeks (p = .005) than their olanzapine counterparts. Future comparative drug studies in this area will further contribute to our understanding of the pathophysiology of mood change and its relationship to psychosis, including clinical relapse and how newer agents may differ in their respective delivery of long-term treatment outcomes.

Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.