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Pharmacopsychiatry
DOI: 10.1055/a-2560-4028
Original Paper

Therapeutic Reference Range for Clozapine Plasma Levels in Parkinson’s Disease or Dementia: A Systematic Review and Individual Participant Data Meta-analysis

Nazar Kuzo 
1   Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Switzerland
,
Marianna Piras
2   Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Switzerland
,
Ulrich C. Lutz
3   Department of Addiction Therapy and Withdrawal, Clinic Schloß Winnenden, Germany
4   University Hospital of Psychiatry and Psychotherapy, Tübingen, Germany
,
Ekkehard Haen
5   Department of Psychiatry and Psychotherapy, Clinical Pharmacology, University of Regensburg, Germany
6   Department of Pharmacology and Toxicology, University of Regensburg, Germany
7   Clinical Pharmacology, Institute AGATE gGmbH, Pentling, Germany
,
Chin B. Eap
2   Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Switzerland
8   School of Pharmaceutical Sciences, University of Geneva, Switzerland
9   Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital, Switzerland
10   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Switzerland
,
Christoph Hiemke
11   Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Germany
12   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany
,
Michael Paulzen
13   Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, and JARA – Translational Brain Medicine, Aachen, Germany
14   Alexianer Center for Mental Health Aachen, Aachen, Germany
,
Georgios Schoretsanitis
1   Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Switzerland
15   The Zucker Hillside Hospital, Department of Psychiatry Research, Northwell Health, Glen Oaks, New York, USA
16   Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA
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Abstract

Introduction

Clozapine is a recommended treatment for psychotic symptoms in patients with Parkinson’s disease (PD) and/or dementia. However, the therapeutic reference range for clozapine in these patients has not been established hitherto.

Materials and Methods

The study was performed in three university hospitals in Germany and Switzerland, including clozapine-treated patients with PD and/or dementia. The primary outcome was tolerability based on reports of adverse drug reactions and/or changes in laboratory tests or electrocardiogram and/or clozapine discontinuation. We meta-analyzed demographic and pharmacokinetic parameters in patients tolerating clozapine well versus not. A meta-analytic summary receiver operating characteristic (SROC) to establish the clozapine upper level associated with poor tolerability was estimated.

Results

We analyzed a total of 99 patients suffering from PD (56.6%) and/or dementia (49.5%) with a mean age of 70.3±9.5 years and 41.4% females; poor tolerability was reported in 26 of 99 patients (26.3%). When comparing patients with and without poor tolerability, there were no differences in age, body mass index, sex, smoking, or clozapine dose, nor did we find statistically significant differences in clozapine levels (standardized mean difference 0.46, 95% confidence interval − 0.04 to 0.96, p=0.07), and heterogeneity was low (I2=0.0%). Clozapine blood levels above 193 ng/mL were associated with poor tolerability (SROC area-under-curve 0.6, sensitivity 39.7%, specificity 79.9%).

Conclusion

One of four patients with PD and/or dementia treated with clozapine did not tolerate clozapine well, which was associated with a trend toward elevated clozapine concentrations. Monitoring drug levels may help to improve tolerability in these patients.

Keywords

therapeutic drug monitoring - clozapine - Parkinson’s disease - dementia

Supplementary Material



Publication History

Received: 30 August 2024

Accepted after revision: 25 January 2025

Article published online:
17 April 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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