C B Eap1,2,3,4,5, G Gründer6, P Baumann7, N Ansermot1, A Conca8,9, E Corruble10,11, S Crettol1, M L Dahl12, J de Leon13, C Greiner14, O Howes15, E Kim16,17, R Lanzenberger18, J H Meyer19, R Moessner20, H Mulder21,22,23,24, D J Müller25,26,27, M Reis28,29, P Riederer30,31, H G Ruhe32,33, O Spigset34,35, E Spina36, B Stegman37, W Steimer38, J Stingl39, S Suzen40, H Uchida41, S Unterecker42, F Vandenberghe1, C Hiemke43. 1. Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 2. Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 3. School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland. 4. Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland. 5. Institute of Pharmaceutical Sciences of Western Switzerland, University of Lausanne, Switzerland, Geneva, Switzerland. 6. Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. 7. Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 8. Department of Psychiatry, Health Service District Bolzano, Bolzano, Italy. 9. Department of Child and Adolescent Psychiatry, South Tyrolean Regional Health Service, Bolzano, Italy. 10. INSERM CESP, Team ≪MOODS≫, Service Hospitalo-Universitaire de Psychiatrie, Universite Paris Saclay, Le Kremlin Bicetre, France. 11. Service Hospitalo-Universitaire de Psychiatrie, Hôpital Bicêtre, Assistance Publique Hôpitaux de Paris, Le Kremlin Bicêtre, France. 12. Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 13. Eastern State Hospital, University of Kentucky Mental Health Research Center, Lexington, KY, USA. 14. Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Germany. 15. King's College London and MRC London Institute of Medical Sciences (LMS)-Imperial College, London, UK. 16. Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea. 17. Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea. 18. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. 19. Campbell Family Mental Health Research Institute, CAMH and Department of Psychiatry, University of Toronto, Toronto, Canada. 20. Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. 21. Department of Clinical Pharmacy, Wilhelmina Hospital Assen, Assen, The Netherlands. 22. GGZ Drenthe Mental Health Services Drenthe, Assen, The Netherlands. 23. Department of Pharmacotherapy, Epidemiology and Economics, Department of Pharmacy and Pharmaceutical Sciences, University of Groningen, Groningen, The Netherlands. 24. Department of Psychiatry, Interdisciplinary Centre for Psychopathology and Emotion Regulation, University of Groningen, Groningen, The Netherlands. 25. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. 26. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 27. Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. 28. Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. 29. Clinical Chemistry and Pharmacology, Skåne University Hospital, Lund, Sweden. 30. Center of Mental Health, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany. 31. Department of Psychiatry, University of Southern Denmark Odense, Odense, Denmark. 32. Department of Psychiatry, Radboudumc, Nijmegen, the Netherlands. 33. Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, Netherlands. 34. Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway. 35. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 36. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 37. Institut für Pharmazie der Universität Regensburg, Regensburg, Germany. 38. Institute for Clinical Chemistry and Pathobiochemistry, Technical University of Munich, Munich, Germany. 39. Institute for Clinical Pharmacology, University Hospital of RWTH Aachen, Germany. 40. Department of Toxicology, Faculty of Pharmacy, Ankara University, Ankara, Turkey. 41. Department of Neuropsychiatry, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. 42. Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany. 43. Department of Psychiatry and Psychotherapy, University Medical Center Mainz, Mainz, Germany.
Abstract
Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient. Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.
Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient. Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.
Entities:
Keywords:
Antidepressants; brain imaging; pharmacogenetics; precision medicine; therapeutic drug monitoring
Authors: Xenia M Hart; Luzie Eichentopf; Xenija Lense; Thomas Riemer; Katja Wesner; Christoph Hiemke; Gerhard Gründer Journal: Front Psychiatry Date: 2021-11-24 Impact factor: 4.157