Pharmacopsychiatry 2022; 55(03): 166
DOI: 10.1055/s-0042-1747652
Abstracts | XIVth Symposium of the Task Force Therapeutic Drug Monitoring of the AGNP

Therapeutic reference range for aripiprazole revised: A systematic review and combined analysis

Authors

  • X.M. Hart

    1   Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

  • C. Hiemke

    2   University Medical Center of Mainz, Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, Mainz, Germany

  • H.W. Clement

    3   University of Freiburg, Department of Child and Adolescent Psychiatry, Freiburg, Germany

  • A. Conca

    4   Sanitario di Bolzano, Servizio Psichiatrico del Comprensorio, Bolzano, Italy

  • L. Eichentopf

    1   Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

  • F. Faltraco

    5   University of Rostock, Department of Psychiatry and Psychotherapy, Rostock, Germany

  • V. Florio

    4   Sanitario di Bolzano, Servizio Psichiatrico del Comprensorio, Bolzano, Italy

  • J. Grüner

    3   University of Freiburg, Department of Child and Adolescent Psychiatry, Freiburg, Germany

  • U. Havemann-Reinecke

    6   Department of Psychiatry and Psychosomatics, University of Göttingen, Göttingen, Germany

  • X. Lense

    1   Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

  • E. Molden

  • M. Paulzen

    7   Alexianer Hospital Aachen, Department of Psychiatry, Psychotherapy and Psychosomatics, Aachen, Germany

  • T.G. Riemer

    8   Berlin Institute of Health, Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany

  • G. Schoretsanitis

    9   University of Zurich, Department of Psychiatry, Psychotherapy and Psychosomatics, Zurich, Switzerland.

  • G. Gründer

    1   Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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Introduction The current reference range for the atypical antipsychotic aripiprazole is 100-350 ng/mL (150-500 ng/mL for the sum of aripiprazole+active metabolite) [1]. The range(s) might be transferable to aripiprazole’s long-acting injectable (LAI) formulation [2]. As published previously, valid reference ranges derive from systematic evaluation of up-to-date literature of the relationship between blood levels, clinical outcomes and receptor occupancy, not solely from experts opinions [3].

Methods We performed a systematic literature review followed by a qualitative and quantitative analysis of the literature to identify a target range for aripiprazole. Studies in humans were selected without restriction to diagnosis. Population-based ranges were computed from concentration data.

Results 54 study cohorts met the eligibility criteria. 29 studies report blood level after oral and 16 after injectable formulations. 13 and 10 of them reported clinical or side effect assessments. Conflicting evidence for a relationship between concentration and efficacy or side effects exists resulting in a grading as low or absent, respectively. The mean aripiprazole concentration across 17 studies (N=3778) was 230.2 ng/mL. When treated under flexible doses, 50% of patients with schizophrenia and related disorders had drug concentrations within a range of 120-273 ng/ml (N=3373). PET studies report quite consistent values of 90% receptor occupancy above 89-110 ng/mL. Several LAI studies have demonstrated concentrations within the current recommended range for oral ARI.

Conclusion Conflicting evidence exists for the concentration/efficacy relationship of aripiprazole. However, including also evidence from TDM and neuroimaging studies, we suggest an optimal target range of 120-270 ng/mL for aripiprazole and 180-370 ng/mL for the sum.



Publication History

Article published online:
16 May 2022

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