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

Xenia Marlene Hart^{1

2}, Gerhard Gründer^{2

3}, Nicolas Ansermot⁴, Andreas Conca⁵, Emmanuelle Corruble^{6

7}, Severine Crettol⁴, Paul Cumming^{8

9}, Ariel Frajerman^{6

7}, Gudrun Hefner¹⁰, Oliver Howes^{11

12}, Marin M Jukic^{13

14}, Euitae Kim¹⁵, Seoyoung Kim¹⁶, Ignazio Maniscalco⁵, Sho Moriguchi², Daniel J Müller^{17

18

19}, Shinichiro Nakajima², Martin Osugo^{11

12}, Michael Paulzen^{20

21}, Henricus Gerardus Ruhe^{22

23}, Maike Scherf-Clavel¹⁷, Georgios Schoretsanitis²⁴, Alessandro Serretti²⁵, Edoardo Spina²⁶, Olav Spigset^{27

28}, Werner Steimer²⁹, Sinan H Süzen³⁰, Hiroyuki Uchida², Stefan Unterecker¹⁷, Frederik Vandenberghe⁴, Celine Verstuyft^{7

31}, Gerald Zernig^{32

33}, Christoph Hiemke³⁴, Chin B Eap^{4

35

36

37}

Affiliations

¹ Department of Molecular Neuroimaging, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
² Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
³ German Center for Mental Health (DZPG), Partner Site Mannheim, Heidelberg, Germany.
⁴ Department of Psychiatry, Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neuroscience, Lausanne University Hospital, Prilly, Switzerland.
⁵ Dipartimento di Psichiatria, Comprensorio Sanitario di Bolzano, Bolzano, Italy.
⁶ Service Hospitalo-Universitaire de Psychiatrie, Hôpital de Bicêtre, Université Paris-Saclay, AP-HP, Le Kremlin-Bicêtre, France.
⁷ Equipe MOODS, Inserm U1018, CESP (Centre de Recherche en Epidémiologie et Sante des Populations), Le Kremlin-Bicêtre, France.
⁸ Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland.
⁹ School of Psychology and Counseling, Queensland University of Technology, Brisbane, Australia.
¹⁰ Forensic Psychiatry, Vitos Clinic for Forensic Psychiatry, Eltville, Germany.
¹¹ Department of Psychosis Studies, IoPPN, King's College London, London, UK.
¹² Faculty of Medicine, Institute of Clinical Sciences (ICS), Imperial College London, London, UK.
¹³ Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
¹⁴ Pharmacogenetics Section, Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
¹⁵ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
¹⁶ Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.
¹⁷ 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.
¹⁹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
²⁰ Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany.
²¹ JARA - Translational Brain Medicine, Alexianer Center for Mental Health, Aachen, Germany.
²² Department of Psychiatry, Radboudumc, Nijmegen, Netherlands.
²³ Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands.
²⁴ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
²⁵ Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
²⁶ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
²⁷ Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
²⁸ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
²⁹ Institute of Clinical Chemistry and Pathobiochemistry, Technical University Munich, Munich, Germany.
³⁰ Department of Pharmaceutic Toxicology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
³¹ Department of Molecular Genetics, Pharmacogenetics and Hormonology, Bicêtre University Hospital Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Paris, France.
³² Department of Pharmacology, Medical University Innsbruck, Hall in Tirol, Austria.
³³ Private Practice for Psychotherapy and Court-Certified Witness, Hall in Tirol, Austria.
³⁴ Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany.
³⁵ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
³⁶ Center for Research and Innovation in Clinical Pharmaceutical Sciences, University of Lausanne, Lausanne, Switzerland.
³⁷ Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Lausanne, Switzerland.

PMID: 38913780
DOI: 10.1080/15622975.2024.2366235

Review

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

Xenia Marlene Hart et al. World J Biol Psychiatry. 2024 Nov.

. 2024 Nov;25(9):451-536.

doi: 10.1080/15622975.2024.2366235. Epub 2024 Sep 1.

Authors

Affiliations

¹ Department of Molecular Neuroimaging, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
² Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
³ German Center for Mental Health (DZPG), Partner Site Mannheim, Heidelberg, Germany.
⁴ Department of Psychiatry, Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neuroscience, Lausanne University Hospital, Prilly, Switzerland.
⁵ Dipartimento di Psichiatria, Comprensorio Sanitario di Bolzano, Bolzano, Italy.
⁶ Service Hospitalo-Universitaire de Psychiatrie, Hôpital de Bicêtre, Université Paris-Saclay, AP-HP, Le Kremlin-Bicêtre, France.
⁷ Equipe MOODS, Inserm U1018, CESP (Centre de Recherche en Epidémiologie et Sante des Populations), Le Kremlin-Bicêtre, France.
⁸ Department of Nuclear Medicine, Bern University Hospital, Bern, Switzerland.
⁹ School of Psychology and Counseling, Queensland University of Technology, Brisbane, Australia.
¹⁰ Forensic Psychiatry, Vitos Clinic for Forensic Psychiatry, Eltville, Germany.
¹¹ Department of Psychosis Studies, IoPPN, King's College London, London, UK.
¹² Faculty of Medicine, Institute of Clinical Sciences (ICS), Imperial College London, London, UK.
¹³ Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
¹⁴ Pharmacogenetics Section, Department of Physiology and Pharmacology, Karolinska Institutet, Solna, Sweden.
¹⁵ Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
¹⁶ Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea.
¹⁷ 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.
¹⁹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
²⁰ Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany.
²¹ JARA - Translational Brain Medicine, Alexianer Center for Mental Health, Aachen, Germany.
²² Department of Psychiatry, Radboudumc, Nijmegen, Netherlands.
²³ Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands.
²⁴ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
²⁵ Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
²⁶ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
²⁷ Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway.
²⁸ Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
²⁹ Institute of Clinical Chemistry and Pathobiochemistry, Technical University Munich, Munich, Germany.
³⁰ Department of Pharmaceutic Toxicology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
³¹ Department of Molecular Genetics, Pharmacogenetics and Hormonology, Bicêtre University Hospital Paris-Saclay, Assistance Publique-Hôpitaux de Paris, Paris, France.
³² Department of Pharmacology, Medical University Innsbruck, Hall in Tirol, Austria.
³³ Private Practice for Psychotherapy and Court-Certified Witness, Hall in Tirol, Austria.
³⁴ Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Mainz, Germany.
³⁵ School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
³⁶ Center for Research and Innovation in Clinical Pharmaceutical Sciences, University of Lausanne, Lausanne, Switzerland.
³⁷ Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Lausanne, Switzerland.

PMID: 38913780
DOI: 10.1080/15622975.2024.2366235

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, specialised tools are used. Three tools have been proven useful to personalise 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 45 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 optimise treatment effects, minimise side effects and ultimately reduce the global burden of diseases, personalised drug treatment has not yet become the standard of care in psychiatry.

Keywords: therapeutic drug monitoring, pharmacogenetic testing, molecular neuroimaging, antipsychotics.

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

Affiliations

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

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