Do differences in atypical antipsychotics matter in routine practice? Medication switch from olanzapine and risperidone to amisulpride.

Atypical antipsychotics are often addressed as one class of drugs, although there are marked differences in their pharmacological profiles. It is unknown how this is seen by practitioners and to what extent they differentiate between the various atypical compounds. In a drug utilization study, 472 schizophrenic outpatients who were switched for individual reasons from either olanzapine or risperidone to amisulpride were monitored. Data on patients, illness and treatment as well as on reasons to switch were collected. The reasons to switch from olanzapine to amisulpride were preferably 'weight gain' (72.6% of the physicians), or the 'expectancy of less weight gain with amisulpride' (84.1%) and 'patient request' (60.2%). Specific reasons to switch from risperidone were 'extrapyramidal symptoms' (58.5%), or the 'expectancy of few extrapyramidal symptoms with amisulpride' (82.5%). In conclusion, this study confirms that physicians do not consider 'atypical antipsychotics' as one homogeneous class of drugs but make differences that reflect the specific pharmacological profiles of the respective drugs.

Therapeutic drug monitoring for optimizing amisulpride therapy in patients with schizophrenia.

Amisulpride is a clinically effective antipsychotic drug in a broad dose range with low propensity for extrapyramidal symptoms (EPS). Daily doses and plasma levels of amisulpride were analyzed within a large-scale therapeutic drug monitoring (TDM) survey to find plasma level ranges for optimized treatment under naturalistic conditions. Data of 378 schizophrenic patients treated with amisulpride (100-1550 mg) were included (40% female). Amisulpride plasma levels were analyzed at steady state; assessment comprised improvement (CGI-I) and side-effects, particularly EPS. For detection of cut-off values regarding non-response or EPS, receiver operating characteristics (ROC) curves were applied and the area under the ROC curve (AUC) was calculated. Amisulpride daily doses (594+/-262 mg) and plasma levels (315+/-277 ng/ml) were significantly correlated (r=0.53; P<0.0001). Patients with non-response to amisulpride (8.9%) had significantly (P<0.05) lower plasma levels (248+/-291 ng/ml) than patients with at least moderate improvement (316+/-253 ng/ml) despite comparable amisulpride doses (628+/-253 vs. 590+/-263 mg). Patients with EPS (14.6%) had significantly (P<0.05) higher amisulpride plasma levels (377+/-290 ng/ml) than patients without EPS (305+/-274 ng/ml) despite similar doses in both groups (595+/-266 vs. 594+/-246 mg). ROC analyses revealed significant predictive properties of amisulpride plasma levels (P<0.05) for non-response (AUC=0.65+/-0.05) and EPS (AUC=0.62+/-0.05), respectively. Daily amisulpride doses did not significantly predict non-response or EPS. Optimal amisulpride plasma level values to avoid non-response and EPS were 100 or 320 ng/ml, respectively. Analysis of clinical utility revealed that blood levels must be analyzed in 7 patients until one patient benefits from the TDM procedure by avoiding non-response or EPS. Although our results were mainly explorative, TDM of amisulpride seems very useful for clinical decision making.