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 tolerabilit y and efficacy of atypical antipsychotic agents were performed in relativel y homogeneous populations that may not be typical of patients seen in clini cal practice. Objective: The Quetiapine Experience with Safety and Tolerability (QUEST) s tudy 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 t rial. Patients were randomized in a 3:1 ratio to receive quetiapine or risp eridone. Doses were adjusted to maximize efficacy and to minimize adverse e vents. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; a dverse events were recorded. Efficacy was assessed using the Clinical Globa l 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 significant ly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperid one 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 eff ects with the 2 drugs, measured by dropout rates, was comparable. At each v isit, 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 l ower HAM-D scores (P=0.028). Conclusions: The results of this study suggest that quetiapine is as effect ive as risperidone for the treatment of psychotic symptoms, is more effecti ve for depressive symptoms, may have a more favorable EPS profile. and has comparable overall tolerability.