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REVIEW ARTICLE

Optimisation of pharmacotherapy in psychiatry through therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests: focus on antipsychotics

XM Hart1 Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;2 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, JapanCorrespondence[email protected] [email protected]
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G Gründer1 Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany;11 German Center for Mental Health (DZPG), partner site Mannheim – Heidelberg – Ulm
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N Ansermot3 Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland
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A Conca4 Dipartimento di Psichiatria, Comprensorio Sanitario di Bolzano, Bolzano, Italy
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E Corruble5 Université Paris-Saclay, AP-HP, Service Hospitalo-Universitaire de Psychiatrie, Hôpital de Bicêtre;6 Equipe MOODS, Inserm U1018, CESP (Centre de Recherche en Epidémiologie et Sante des Populations), Le Kremlin-Bicêtre, France
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S Crettol7 Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland
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P Cumming8 Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland;9 School of Psychology and Counseling, Queensland University of Technology, Brisbane, Australia
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G Hefner10 Vitos Clinic for Forensic Psychiatry, Forensic Psychiatry, Eltville, Germany
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A Frajerman5 Université Paris-Saclay, AP-HP, Service Hospitalo-Universitaire de Psychiatrie, Hôpital de Bicêtre;6 Equipe MOODS, Inserm U1018, CESP (Centre de Recherche en Epidémiologie et Sante des Populations), Le Kremlin-Bicêtre, France
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O Howes12 Department of Psychosis Studies, IoPPN, King’s College London, De Crespigny Park, London, SE5 8AF, UK;13 Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, LondonW12 0NN, UKORCID Iconhttps://orcid.org/0000-0002-2928-1972
ORCID Icon,
M Jukic14 Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia and Pharmacogenetics Section, Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden
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E Kim15 Department of Psychiatry, Seoul National University College of Medicine, Republic of Korea
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S Kim16 Department of Neuropsychiatry, Seoul National University Bundang Hospital, Republic of Korea
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I Manisalco4 Dipartimento di Psichiatria, Comprensorio Sanitario di Bolzano, Bolzano, Italy
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S Moriguchi2 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
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DJ Müller17 Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany;18 Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada, and Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
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S Nakajima2 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
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M Osugo12 Department of Psychosis Studies, IoPPN, King’s College London, De Crespigny Park, London, SE5 8AF, UK;13 Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, Du Cane Road, LondonW12 0NN, UK
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M Paulzen19 Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University;20 JARA - Translational Brain Medicine, Aachen, Germany; Alexianer Center for Mental Health, Aachen, Germany
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HG Ruhe21 Department of psychiatry, Radboudumc, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands
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M Scherf-Clavel17 Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
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G Schoretsanitis22 Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, 8032Zurich, SwitzerlandORCID Iconhttps://orcid.org/0000-0002-3851-4117
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A Serretti23 Department of Medicine and Surgery, Kore University of Enna, ItalyORCID Iconhttps://orcid.org/0000-0003-4363-3759
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E Spina26 Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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O Spigset25 Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway, and Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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W Steimer27 Institute of Clinical Chemistry and Pathobiochemistry, Technical University Munich, Munich, Germany
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HS Süzen24 Department of Pharmaceutic Toxicology, Faculty of Pharmacy, Ankara University, Ankara, Turkey
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H Uchida2 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
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S Unterecker17 Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
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F Vandenberghe28 Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland
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C Verstuyft29 Department of Molecular Genetics, Pharmacogenetics and Hormonology Bicêtre University Hospital Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, F-94275, France;30 CESP, MOODS Team, INSERM UMR 1018, Medicine Faculty, Paris-Saclay University, Le Kremlin Bicêtre, France
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G Zernig31 Department of Pharmacology, Medical University Innsbruck; Private Practice for Psychotherapy and Court-Certified Witness, Hall in Tirol, Austria
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C Hiemke32 Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany
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CB Eap33 Unit of Pharmacogenetics and Clinical Psychopharmacology, Department of Psychiatry, Centre for Psychiatric Neuroscience, Lausanne University Hospital, University of Lausanne, 1008Prilly, Switzerland;34 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland;35 Center for Research and Innovation in Clinical Pharmaceutical Sciences, University of Lausanne, Lausanne, Switzerland;36 Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Lausanne, SwitzerlandCorrespondence[email protected] [email protected]
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Received 04 Nov 2023, Accepted 06 Jun 2024, Accepted author version posted online: 24 Jun 2024
 
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Accepted author version

Abstract

Background: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialized tools are used. Three tools have been proven useful to personalize drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging.

Methods: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 50 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)).

Results: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings.

Conclusion: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimize treatment effects, minimize side effects and ultimately reduce the global burden of diseases, personalized drug treatment has not yet become the standard of care in psychiatry.

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As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.

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