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

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Ethics and approval

The study protocol was approved by the Ethics Committee of the University Hospital of Tuebingen (project number 473/2008A).

Conflicts of interest

The authors declare that they have no conflict of interest.

Sponsors

None.

Contributions of authors

UCL: conception and planning of the study, interpretation of data and preparing the initial draft of the manuscript. AS: acquisition of data (retrospective chart review) and statistical analyses. GW, DA and GF: acquisition of data (laboratory analyses and aid in retrospective chart review). TG: conception of the study and interpretation of data. KNK: acquisition and interpretation of data. AB: conception of the study, analysis and interpretation of data. All authors revised the manuscript critically for important intellectual content, and read and approved the final manuscript.

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Authors and Affiliations

  1. University Hospital of Psychiatry and Psychotherapy, Calwerstr. 14, 72076, Tuebingen, Germany

    Ulrich C. Lutz, Ahmad Sirfy, Gerlinde Wiatr, Danuta Altpaß, Gisbert Farger & Anil Batra

  2. Psychiatric Hospital, Clinic for Addictive Behaviour, Schloßstr. 50, 71364, Winnenden, Germany

    Ulrich C. Lutz

  3. Klinikum Erding, Clinic for Internal Medicine, Bajuwarenstraße 5, 85435, Erding, Germany

    Ahmad Sirfy

  4. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany

    Thomas Gasser & Kathrin N. Karle

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  1. Ulrich C. Lutz
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Correspondence to Ulrich C. Lutz.

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Lutz, U.C., Sirfy, A., Wiatr, G. et al. Clozapine serum concentrations in dopamimetic psychosis in Parkinson’s disease and related disorders. Eur J Clin Pharmacol 70, 1471–1476 (2014). https://doi.org/10.1007/s00228-014-1772-0

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  • DOI: https://doi.org/10.1007/s00228-014-1772-0

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