Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina.
OBJECTIVE
The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal 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, open-label, prospective observational study. Data were collected by 293 psychiatrists 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 Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score < or = 4.


RESULTS
A total of 2657 patients were included in the analysis. The initial 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-treated patients (36.9%) experienced EPS compared with RIS-treated (49.6%) and HAL-treated (76.0%) patients (P < or = 0.001). A significantly lower proportion of patients in the OLZ group (47.8%) experienced adverse events compared with patients in the RIS (57.2%) and HAL (79.8%) groups (P < or = 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 > or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6) compared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001).


CONCLUSIONS
The mean daily doses recorded in this analysis based on data from a naturalistic setting are consistent with recommendations based on clinical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and less likely to use concomitant anticholinergic medications. OLZ-treated patients were also more likely to respond to treatment than were RIS-treated patients.
Sacristán
J A
JA
Clinical Research Department, Lilly S.A., Madrid, Spain. sacristan_jose@lilly.com
Gómez
J C
JC
Montejo
A L
AL
Vieta
E
E
Gregor
K J
KJ
D000328:Adult; D000553:Ambulatory Care; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001569:Benzodiazepines; D004363:Drug Utilization; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D000077152:Olanzapine; D017891:Pharmacoepidemiology; D010890:Pirenzepine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010818:Practice Patterns, Physicians'; D011446:Prospective Studies; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine