title: Therapeutic monitoring of new antipsychotic drugs.
abstract: Typical antipsychotic drugs qualify for therapeutic drug monitoring (TDM) primarily for the following reasons: control of compliance and avoidance of extrapyramidal side effects by keeping chronic exposure to minimal effective blood levels. For the atypical antipsychotic clozapine, drug safety is another reason to use TDM. With regard to the new antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole, which have been introduced in the clinic during the last few years, the rationale to use TDM is a matter of debate. Positron emission tomography (PET), which enables measurement of the occupancy of dopamine D2 receptors, revealed that receptor occupancy correlated better with plasma concentrations than with doses of the antipsychotics. Regarding plasma levels related to therapeutic effects, optimal concentrations have been established for clozapine (350-600 ng/mL), risperidone (20-60 ng/mL), and olanzapine (20-80 ng/mL) but not for the other new antipsychotics. Studies that included analyses of drug levels in blood reported mean concentrations of 68 ng/mL for quetiapine and 317 ng/mL for amisulpride under therapeutic doses of the antipsychotic drugs. For ziprasidone or aripriprazole, data on therapeutic drug concentrations are so far lacking. In conclusion, evidence is growing that TDM may improve efficacy and safety in patients treated with the new antipsychotic drugs, especially when patients do not respond or develop side effects under therapeutic doses. The few reported investigations, however, need to be confirmed and extended.
authors.affiliation: Department of Psychiatry, University of Mainz, D-55101 Mainz, Germany. hiemke@mail.uni-mainz.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Dragicevic
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hätter
authors.forename: Julia
authors.initials: J
authors.lastname: Sachse
authors.forename: Ingo
authors.initials: I
authors.lastname: Vernaleken
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Müller
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2