A discussion of 2 double-blind studies comparing risperidone and quetiapine in patients with schizophrenia.

Sir: We read with great interest the recent article by Zhong and colleagues 1 reporting results of a trial comparing quetiapine and risperidone for the treatment of schizophrenia. In that double-blind, 8-week study, there was a statistically significant difference favoring risperidone on the change at endpoint on the Positive and Negative Syndrome Scale (PANSS) positive symptoms subscale (an a priori secondary efficacy measure). In the same month, we 2 published similar findings from a double-blind, placebo-controlled trial comparing these 2 atypical antipsy-chotics in patients with schizophrenia experiencing an acute ex-acerbation requiring hospitalization (least squares mean ± SE change from baseline to endpoint of the monotherapy phase for PANSS positive symptoms: –8.7 ± 0.5 with risperidone and –5.9 ± 0.5 with quetiapine; p < .01). The complementary results from these 2 independent studies 1,2 using comparable dosing regimens support an efficacy benefit with risperidone compared with quetiapine for positive symptoms. Results from the primary efficacy measure (change in PANSS total score) are also consistent between the 2 studies, demonstrating greater improvement with risperidone. While the difference was statistically significant in our report 2 and not statistically significant in that of Zhong et al., 1 methodological differences as described later may underlie this seeming discrepancy. Another important clinical between-treatment difference observed by Zhong et al. 1 was the proportion of patients withdrawing from the study due to lack of efficacy (24.3% for quetia-pine vs. 13.7% for risperidone). Although the authors reported that " the proportion of patients withdrawing due to lack of efficacy was higher with quetiapine than with risperidone, " 1(p1096) our χ 2 analysis of these data found the difference to be significant (p < .001). This difference between treatment groups was consistent with the PANSS last-observation-carried-forward (LOCF) results. The tolerability results reported by Zhong et al. 1 suggested no unexpected adverse events, with profiles as expected with these agents, and were also similar to those that we reported. 2 While the incidence of spontaneously reported extrapyramidal symptoms (EPS) was significantly higher in the risperidone group as compared with the quetiapine group, the p.r.n. use of anticholin-ergic agents for these symptoms was low (6.9% and 5.6%, respectively), with no significant difference between groups. In contradiction to reports of EPS, improvements in mean Abnormal Involuntary Movement Scale and Simpson-Angus Scale total scores (standardized measures of EPS) were observed in both groups. A between-group difference of ≈0.1 was reported for change from …