Doses of olanzapine, risperidone, and haloperidol used in clinical practice: Results of a prospective pharmacoepidemiologic study

Objective: The objectives of this study were to determine the doses of olan zapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical pra ctice in outpatients with schizophrenia and the rates of occurrence of extr apyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications. Methods: The present study involved a subset of patients from a 6-month, op en-label, prospective observational study. Data were collected by 293 psych iatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scal e and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of greater than or equal to 2 points on the CGI, with a final CGI score less than or equal to 4. Results: A total of 2657 patients were included in the analysis. The initia l and overall mean daily doses for the 3 groups were as follows: OLZ, 12.2 and 13.0 mg, respectively; RIS, 5.2 and 5.4 mg; and HAL, 13.9 and 13.6 mg. Initial and overall median daily doses were the same in each group: OLZ, 10 mg; RIS, 6 mg; and HAL, 10 mg. A significantly lower proportion of OLZ-tre ated patients (36.9%) experienced EPS compared with RIS-treated (49.6%) and HAL-treated (76.0%) patients (P less than or equal to 0.001). A significan tly lower proportion of patients in the OLZ group (47.8%) experienced adver se events compared with patients in the RIS (57.2%) and HAL (79.8%) groups (P less than or equal to 0.001). A significantly greater proportion of OLZ- treated patients (37.3%) were responders compared with RIS-treated patients (31.5%) (P < 0.05). In all 3 groups, patients who had an initial CGI score greater than or equal to 5 received significantly higher overall mean dail y doses than did patients with an initial CGI score <5 (P < 0.001). A signi ficantly lower proportion of OLZ-treated patients (10.2%) were receiving co ncomitant anticholinergic medication at the end of the study (month 6) comp ared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001). Conclusion: The mean daily doses recorded in this analysis based on data fr om a naturalistic setting are consistent with recommendations based on clin ical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and le ss likely to use concomitant anticholinergic medications. OLZ-treated patie nts were also more likely to respond to treatment than were RIS-treated pat ients.