A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: The Quetiapine Experience with Safety and Tolerability (QUEST) study

Background: The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice. Objective: The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms. Methods: This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D). Results: A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone, Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P=0.028). Conclusions: The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile. and has comparable overall tolerability.