title: Therapeutic drug monitoring for optimizing amisulpride therapy in patients with schizophrenia.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Mainz, Untere Zahlbacher Str. 8, D-55131 Mainz, Germany. mjmueller@gmx.de
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Müller
authors.forename: Boris
authors.initials: B
authors.lastname: Regenbogen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Härtter
authors.forename: Franz X
authors.initials: FX
authors.lastname: Eich
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D004409:Dyskinesia, Drug-Induced / Q000097:blood / Q000175:diagnosis; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D012372:ROC Curve; D012189:Retrospective Studies; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D013223:Statistics as Topic; D013469:Sulpiride / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride