Clozapine serum concentrations in dopamimetic psychosis in Parkinson's disease and related disorders.

ABSTRACT

PURPOSE: Psychotic symptoms in Parkinson's disease (PD) caused by dopamimetic treatment are a relevant clinical problem. As clozapine does not cause extrapyramidal side effects, it is suitable for treatment of dopamimetic psychosis. The main aim of the present study was (1) to establish an indication-specific recommendation for therapeutic reference range of clozapine among patients with dopamimetic psychosis in PD and related disorders. Secondary goals were (2) to test whether clozapine therapy is safe and calculable despite pharmacokinetic changes expected in the study population and (3) to assess influencing variables on clozapine serum levels. METHODS: We carried out a retrospective chart review of patients suffering from dopamimetic psychosis as well as Lewy body dementia treated with clozapine. We extracted demographic and clinical data as well as results from therapeutic drug monitoring that was carried out via high-performance liquid chromatography in order to analyse clozapine and norclozapine serum concentrations. RESULTS: n = 35 patients could be identified and were included in the study. Mean age was 72.4 years. Clozapine treatment for patients with dopamimetic psychosis in PD and related disorders seems to be safe and calculable. Mean clozapine serum concentration was 77.9 ng/ml (SD 63.4 ng/ml). Clozapine dose is significantly correlated with serum clozapine concentration (r = 0.35; R (2) = 0.122). Women showed lower clozapine serum concentrations although they received higher weight-corrected clozapine doses. CONCLUSIONS: We suggest an orienting indication-specific therapeutic reference range of 15-141 ng/ml among PD patients with dopamimetic psychosis. Therapeutic drug monitoring is recommended and might help to minimize the risk of adverse events by screening for unexpectedly high serum concentrations of clozapine.