Plasma levels of second-generation antipsychotics and clinical response in acute psychosis: a review of the literature.

OBJECTIVE

The objective of the study is to assess the relationships between plasma concentrations (Cps) of second-generation antipsychotics (SGAs) and clinical outcome in order to establish the clinical value of therapeutic drug monitoring.

METHOD: In April 2012, we searched PubMed and MEDLINE databases for English-language articles using the keywords risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, paliperidone, iloperidone, asenapine, lurasidone, therapeutic drug monitoring, serum level, and plasma level. One hundred and ninety-one articles were retrieved from the initial search. Articles were selected for inclusion if they involved an attempt to correlate Cps with efficacy measures, if they were prospective in nature, and if they examined patients experiencing an acute exacerbation of a psychotic illness. Ultimately 11 articles were selected.

RESULTS

Of the nine compounds involved in the search, only four were included in relevant articles, and only two of these were involved in multiple trials. No studies involving the most recently developed compounds (paliperidone, iloperidone, asenapine, and lurasidone) were identified. Studies varied widely in methodology, with only four studies adopting a fixed-dose model. Results differed considerably between studies regarding both clinical and adverse effects, with 6 of the 11 studies revealing a positive correlation between Cps and response.

CONCLUSIONS

The utility of therapeutic drug monitoring of SGAs (other than clozapine) remains an open question, although limited evidence from fixed-dose studies is encouraging. We discuss the potentially significant clinical value of antipsychotic Cps and the consequent need for further research in this area.