. 2025 Jan 10;68(1):e17.

doi: 10.1192/j.eurpsy.2024.1816.

The time has come for revising the rules of clozapine blood monitoring in Europe. A joint expert statement from the European Clozapine Task Force

Hélène Verdoux¹, Robert A Bittner², Alkomiet Hasan^{3

4}, Mishal Qubad², Elias Wagner^{3

5}, Alexis Lepetit^{6

7

8}, Manuel Arrojo-Romero⁹, Christian Bachmann¹⁰, Marieke Beex-Oosterhuis¹¹, Jan Bogers¹², Andreja Celofiga¹³, Dan Cohen^{14

15}, Domenico de Berardis¹⁶, Marc de Hert^{17

18

19

20}, Carlos de Las Cuevas²¹, Bjørn H Ebdrup^{22

23}, Konstantinos N Fountoulakis²⁴, Daniel Guinart^{25

26

27}, Dolores Keating²⁸, Miloslav Kopeček^{29

30}, John Lally^{31

32

33}, Judit Lazáry³⁴, Jurjen J Luykx^{35

36

37

38}, Olalla Maronas Amigo^{39

40

41

42}, Espen Molden^{43

44}, Jimmi Nielsen⁴⁵, Brian O'Donoghue^{46

47}, Pierre Oswald⁴⁸, Flavian S Radulescu⁴⁹, Christopher Rohde^{50

51}, Marina Sagud^{52

53}, Emilio J Sanz^{54

55}, Ivona Šimunović Filipčić^{56

57}, Iris E Sommer⁵⁸, Heidi Taipale^{59

60

61}, Jari Tiihonen^{59

60

62}, Heli Tuppurainen⁵⁹, Selene Veerman^{63

14}, Alina Wilkowska⁶⁴, Edoardo Spina⁶⁵, Peter Schulte^{14

66}

Affiliations

¹ French Clozapine Task Force, University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Bordeaux, France.
² Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt am Main, Germany.
³ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany.
⁴ DZPG (German Center for Mental Health), Partner Site, Munich/Augsburg, Germany.
⁵ Evidence-based Psychiatry and Psychotherapy, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
⁶ French Clozapine Task Force; ACPPA Group, Francheville, France.
⁷ Hospices Civils de Lyon, Hôpital des Charpennes, Villeurbanne, France.
⁸ Institut des Sciences Cognitives Marc Jeannerod, CNRS, Bron, France.
⁹ Department of Psychiatry, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.
¹⁰ Department of Child and Adolescent Psychiatry, Ulm University, Ulm, Germany.
¹¹ Department of Hospital Pharmacy, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
¹² Mental Health Organization Rivierduinen, Leiden, The Netherlands.
¹³ Department of Psychiatry, University Medical Centre Maribor, Maribor, Slovenia.
¹⁴ Dutch Clozapine Collaboration Group, Alkmaar, The Netherlands.
¹⁵ Esdege-Reigersdaal, Heerhugowaard, The Netherlands.
¹⁶ NHS, Department of Mental Health, G. Mazzini Hospital, Teramo, Italy.
¹⁷ University Psychiatric Center Katholieke Universiteit Leuven, Kortenberg, Belgium.
¹⁸ Department of Neurosciences, Centre for Clinical Psychiatry, Katholieke Universiteit Leuven, Leuven, Belgium.
¹⁹ Leuven Brain Institute, Katholieke Universiteit Leuven, Leuven, Belgium.
²⁰ Antwerp Health Law and Ethics Chair, University of Antwerp, Antwerp, Belgium.
²¹ Department of Internal Medicine, Dermatology and Psychiatry, School of Medicine, University of La Laguna, Canary Islands, Spain.
²² Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark.
²³ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁴ 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²⁵ Institut de Salut Mental, Hospital del Mar, Barcelona, Spain.
²⁶ Programa Recerca en Salut Mental, Hospital del Mar Research Institute, CIBERSAM, Barcelona, Spain.
²⁷ The Donald and Barbara Zucker School of Medicine, Northwell Health, New York, NY, USA.
²⁸ Saint John of God Hospital, Stillorgan, Co. Dublin, Dublin, Ireland.
²⁹ National Institute of Mental Health, Klecany, Czech Republic.
³⁰ Department of Psychiatry, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
³¹ Department of Psychiatry, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
³² Department of Psychiatry, St Vincent's Hospital Fairview, Dublin, Ireland.
³³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
³⁴ Nyírő Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary.
³⁵ Department of Psychiatry, Amsterdam UMC, Amsterdam, The Netherlands.
³⁶ GGZ inGeest Mental Health Care, Amsterdam, The Netherlands.
³⁷ Amsterdam Neuroscience (Mood, Anxiety, Psychosis, Stress & Sleep program) and Amsterdam Public Health (Mental Health program) Research Institutes, Amsterdam, The Netherlands.
³⁸ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience Maastricht University Medical Center, Maastricht, The Netherlands.
³⁹ Pharmacogenomics and Drug Discovery (GenDeM), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
⁴⁰ Genomic Medicine Group, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
⁴¹ Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
⁴² Galician Public Foundation of Genomic Medicine (FPGMX), Galician Healthcare Service (SERGAS), Santiago de Compostela, Spain.
⁴³ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
⁴⁴ Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
⁴⁵ Mental Health Centre Glostrup, Copenhagen University Hospital, Copenhagen, Denmark.
⁴⁶ Department of Psychiatry, University College Dublin, Dublin, Ireland.
⁴⁷ Department of Psychiatry, St Vincent's University Hospital, Dublin, Ireland.
⁴⁸ Department of Psychiatry, Hôpital Universitaire de Bruxelles, Bruxelles, Belgium.
⁴⁹ Center for Drug Sciences, Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
⁵⁰ Department of Affective Disorders, Aarhus University, Hospital - Psychiatry, Aarhus, Denmark.
⁵¹ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁵² Department of Psychiatry, School of Medicine, University of Zagreb, Zagreb, Croatia.
⁵³ Department for Psychiatry and Psychological Medicine, University Hospital Center Zagreb, Zagreb, Croatia.
⁵⁴ Department of Physical Medicine and Pharmacology, School of Medicine, Universidad de La Laguna, Canary Islands, Spain.
⁵⁵ Hospital Universitario de Canarias, Tenerife, Spain.
⁵⁶ Department of Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
⁵⁷ Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
⁵⁸ Department of Neuroscience, and Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵⁹ Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
⁶⁰ Department of Clinical Neuroscience, Karolinska Institutet, and Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden.
⁶¹ School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
⁶² Neuroscience Center, University of Helsinki, Helsinki, Finland.
⁶³ Mental Health Services Noord-Holland-Noord, Schagen, The Netherlands.
⁶⁴ Department of Psychiatry, Medical University of Gdańsk, Gdańsk, Poland.
⁶⁵ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁶⁶ Mental Health Services Noord-Holland-Noord, Alkmaar, The Netherlands.

PMID: 39788917
PMCID: PMC11822956
DOI: 10.1192/j.eurpsy.2024.1816

The time has come for revising the rules of clozapine blood monitoring in Europe. A joint expert statement from the European Clozapine Task Force

Hélène Verdoux et al. Eur Psychiatry. 2025.

. 2025 Jan 10;68(1):e17.

doi: 10.1192/j.eurpsy.2024.1816.

Authors

Affiliations

¹ French Clozapine Task Force, University of Bordeaux, Inserm, Bordeaux Population Health Research Center, Bordeaux, France.
² Goethe University Frankfurt, University Hospital, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Frankfurt am Main, Germany.
³ Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, University of Augsburg, Augsburg, Germany.
⁴ DZPG (German Center for Mental Health), Partner Site, Munich/Augsburg, Germany.
⁵ Evidence-based Psychiatry and Psychotherapy, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
⁶ French Clozapine Task Force; ACPPA Group, Francheville, France.
⁷ Hospices Civils de Lyon, Hôpital des Charpennes, Villeurbanne, France.
⁸ Institut des Sciences Cognitives Marc Jeannerod, CNRS, Bron, France.
⁹ Department of Psychiatry, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.
¹⁰ Department of Child and Adolescent Psychiatry, Ulm University, Ulm, Germany.
¹¹ Department of Hospital Pharmacy, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
¹² Mental Health Organization Rivierduinen, Leiden, The Netherlands.
¹³ Department of Psychiatry, University Medical Centre Maribor, Maribor, Slovenia.
¹⁴ Dutch Clozapine Collaboration Group, Alkmaar, The Netherlands.
¹⁵ Esdege-Reigersdaal, Heerhugowaard, The Netherlands.
¹⁶ NHS, Department of Mental Health, G. Mazzini Hospital, Teramo, Italy.
¹⁷ University Psychiatric Center Katholieke Universiteit Leuven, Kortenberg, Belgium.
¹⁸ Department of Neurosciences, Centre for Clinical Psychiatry, Katholieke Universiteit Leuven, Leuven, Belgium.
¹⁹ Leuven Brain Institute, Katholieke Universiteit Leuven, Leuven, Belgium.
²⁰ Antwerp Health Law and Ethics Chair, University of Antwerp, Antwerp, Belgium.
²¹ Department of Internal Medicine, Dermatology and Psychiatry, School of Medicine, University of La Laguna, Canary Islands, Spain.
²² Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center, Glostrup, Copenhagen University Hospital - Mental Health Services CPH, Copenhagen, Denmark.
²³ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁴ 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
²⁵ Institut de Salut Mental, Hospital del Mar, Barcelona, Spain.
²⁶ Programa Recerca en Salut Mental, Hospital del Mar Research Institute, CIBERSAM, Barcelona, Spain.
²⁷ The Donald and Barbara Zucker School of Medicine, Northwell Health, New York, NY, USA.
²⁸ Saint John of God Hospital, Stillorgan, Co. Dublin, Dublin, Ireland.
²⁹ National Institute of Mental Health, Klecany, Czech Republic.
³⁰ Department of Psychiatry, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
³¹ Department of Psychiatry, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
³² Department of Psychiatry, St Vincent's Hospital Fairview, Dublin, Ireland.
³³ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
³⁴ Nyírő Gyula National Institute of Psychiatry and Addictions, Budapest, Hungary.
³⁵ Department of Psychiatry, Amsterdam UMC, Amsterdam, The Netherlands.
³⁶ GGZ inGeest Mental Health Care, Amsterdam, The Netherlands.
³⁷ Amsterdam Neuroscience (Mood, Anxiety, Psychosis, Stress & Sleep program) and Amsterdam Public Health (Mental Health program) Research Institutes, Amsterdam, The Netherlands.
³⁸ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience Maastricht University Medical Center, Maastricht, The Netherlands.
³⁹ Pharmacogenomics and Drug Discovery (GenDeM), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
⁴⁰ Genomic Medicine Group, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain.
⁴¹ Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.
⁴² Galician Public Foundation of Genomic Medicine (FPGMX), Galician Healthcare Service (SERGAS), Santiago de Compostela, Spain.
⁴³ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
⁴⁴ Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
⁴⁵ Mental Health Centre Glostrup, Copenhagen University Hospital, Copenhagen, Denmark.
⁴⁶ Department of Psychiatry, University College Dublin, Dublin, Ireland.
⁴⁷ Department of Psychiatry, St Vincent's University Hospital, Dublin, Ireland.
⁴⁸ Department of Psychiatry, Hôpital Universitaire de Bruxelles, Bruxelles, Belgium.
⁴⁹ Center for Drug Sciences, Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
⁵⁰ Department of Affective Disorders, Aarhus University, Hospital - Psychiatry, Aarhus, Denmark.
⁵¹ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁵² Department of Psychiatry, School of Medicine, University of Zagreb, Zagreb, Croatia.
⁵³ Department for Psychiatry and Psychological Medicine, University Hospital Center Zagreb, Zagreb, Croatia.
⁵⁴ Department of Physical Medicine and Pharmacology, School of Medicine, Universidad de La Laguna, Canary Islands, Spain.
⁵⁵ Hospital Universitario de Canarias, Tenerife, Spain.
⁵⁶ Department of Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
⁵⁷ Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
⁵⁸ Department of Neuroscience, and Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁵⁹ Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.
⁶⁰ Department of Clinical Neuroscience, Karolinska Institutet, and Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden.
⁶¹ School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
⁶² Neuroscience Center, University of Helsinki, Helsinki, Finland.
⁶³ Mental Health Services Noord-Holland-Noord, Schagen, The Netherlands.
⁶⁴ Department of Psychiatry, Medical University of Gdańsk, Gdańsk, Poland.
⁶⁵ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁶⁶ Mental Health Services Noord-Holland-Noord, Alkmaar, The Netherlands.

PMID: 39788917
PMCID: PMC11822956
DOI: 10.1192/j.eurpsy.2024.1816

Abstract

The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA's blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

Keywords: blood monitoring; clozapine; regulation; treatment-resistant schizophrenia.

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Conflict of interest statement

The following authors declare none: Hélène VERDOUX, Robert BITTNER, Alexis LEPETIT, Manuel ARROJO-ROMERO, Christian BACHMANN, Marieke BEEX-OOSTERHUIS, Jan BOGERS, Dan COHEN, Marc DE HERT, Carlos DE LAS CUEVAS, John LALLY, Dolores KEATING, Judit LAZÁRY, Jurjen J. LUYKX, Olalla MARONAS AMIGO, Jimmi NIELSEN, Brian O’DONOGHUE, Pierre OSWALD, Flavian S RADULESCU, Christopher ROHDE, Emilio J. SANZ, Ivona ŠIMUNOVIĆ FILIPČIĆ, Iris E. SOMMER, Selene VEERMAN, Edoardo SPINA, Peter SCHULTE; Alkomiet HASAN is editor of the German (DGPPN) schizophrenia treatment guidelines, first author of the WFSBP schizophrenia treatment guidelines; on advisory boards of and speaker fees from AbbVie, Advanz (speaker fees only), Janssen-Cilag, Lundbeck, Recordati, Rovi, Teva, and Otsuka; Mishal QUBAD has received speaker fees from Recordati; Elias WAGNER was invited to advisory boards from Recordati, Teva and Boehringer Ingelheim; Andreja CELOFIGA participated in lectures for the following companies: Krka, Bonifar, Viatris, Gedeon Richter, Lek, and Lundbeck-Pharma; Domenico DE BERARDIS was speaker/consultant for Angelini, Innova Pharma, Janssen, Lundbeck, Viatris, Rovi and Otsuka Konstantinos; Bjørn EBDRUP is part of the Advisory Board of Boehringer Ingelheim, Lundbeck Pharma A/S; and has received lecture fees from Boehringer Ingelheim, Otsuka Pharma Scandinavia AB, and Lundbeck Pharma A/S; N. FOUNTOULAKIS has received in the past grants, served as a consultant, advisor, or CME speaker, or received support to attend congresses by the following entities: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Pfizer, the Pfizer Foundation, Sanofi-Aventis, Servier, Shire, and others; Daniel GUINART has been a consultant and/or advisor of has received honoraria from Angelini, Janssen, Lundbeck/Lundbeck Foundation, Otsuka, Teva; he currently receives funding from the European Commission (HORIZON EUROPE) and from the Instituto de Salud Carlos III (ISCIII); Miloslav KOPEČEK is member of advisory board and speakers’ honoraria from Angeliny Pharma and Lundbeck; Espen MOLDEN has received speaker’s honorarium from Lundbeck and Otsuka; Marina SAGUD has presented lectures for the following companies: Angelini, Belupo, Gedeon Richter, Johnson & Johnson, Krka Farma d.o.o., Lundbeck, Pliva d.o.o., and Viatris; participated in clinical trials as an principal investigator for Boeringer Ingelheim; and is a member of the advisory board of Lundbeck and Pliva; Heidi TAIPALE has participated in research projects funded by grants from Janssen to her employing institution; and has received lecture fees from Gedeon Richter, Janssen, Lundbeck and Otsuka; Jari TIIHONEN has participated in research projects funded by grants from Janssen to his employing institution; has served as a consultant for Healthcare Global Village, HLS Therapeutics, Janssen, Lundbeck, Orion, Teva, and WebMD Global; and has received honoraria from Janssen, Lundbeck, and Otsuka; Heli TUPPURAINEN has received speakers fee from Lundbeck; Alina WILKOWSKA has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen- Cilag, Lundbeck, Polpharma, Sanofi, Termedia, and Valeant.

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The time has come for revising the rules of clozapine blood monitoring in Europe. A joint expert statement from the European Clozapine Task Force

Affiliations

The time has come for revising the rules of clozapine blood monitoring in Europe. A joint expert statement from the European Clozapine Task Force

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Abstract

Conflict of interest statement

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