An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

doi:10.1055/a-1625-6388

. 2022 Mar;55(2):73-86.

doi: 10.1055/a-1625-6388. Epub 2021 Dec 15.

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

Jose de Leon^{1

2

3

4}, Georgios Schoretsanitis^{5

6}, Robert L Smith⁷, Espen Molden^{7

8}, Anssi Solismaa^{9

10}, Niko Seppälä¹¹, Miloslav Kopeček^{12

13}, Patrik Švancer^{12

13}, Ismael Olmos¹⁴, Carina Ricciardi¹⁵, Celso Iglesias-Garcia^{16

17}, Ana Iglesias-Alonso¹⁸, Edoardo Spina¹⁹, Can-Jun Ruan^{20

21}, Chuan-Yue Wang^{21

22}, Gang Wang²¹, Yi-Lang Tang^{23

24}, Shih-Ku Lin^{25

26}, Hsien-Yuan Lane^{27

28

29}, Yong Sik Kim³⁰, Se Hyun Kim³¹, Anto P Rajkumar^{32

33}, Dinora F González-Esquivel³⁴, Helgi Jung-Cook^{34

35}, Trino Baptista³⁶, Christopher Rohde^{37

38}, Jimmi Nielsen³⁹, Hélène Verdoux⁴⁰, Clelia Quiles⁴⁰, Emilio J Sanz^{41

42}, Carlos De Las Cuevas⁴³, Dan Cohen^{44

45}, Peter F J Schulte^{44

46}, Aygün Ertuğrul⁴⁷, A Elif Anıl Yağcıoğlu⁴⁷, Nitin Chopra^{48

49}, Betsy McCollum⁵⁰, Charles Shelton^{2

50}, Robert O Cotes²³, Arun R Kaithi⁵¹, John M Kane^{6

52}, Saeed Farooq⁵³, Chee H Ng⁵⁴, John Bilbily⁵⁵, Christoph Hiemke⁵⁶, Carlos López-Jaramillo^{57

58}, Ian McGrane⁵⁹, Fernando Lana^{60

61}, Chin B Eap^{62

63

64

65}, Manuel Arrojo-Romero⁶⁶, Flavian Ş Rădulescu⁶⁷, Erich Seifritz⁵, Susanna Every-Palmer^{68

69}, Chad A Bousman⁷⁰, Emmanuel Bebawi^{71

72}, Rahul Bhattacharya^{73

74}, Deanna L Kelly⁷⁵, Yuji Otsuka⁷⁶, Judit Lazary⁷⁷, Rafael Torres⁷⁸, Agustin Yecora⁷⁹, Mariano Motuca⁸⁰, Sherry K W Chan^{81

82}, Monica Zolezzi⁸³, Sami Ouanes⁸⁴, Domenico De Berardis⁸⁵, Sandeep Grover⁸⁶, Ric M Procyshyn⁸⁷, Richard A Adebayo⁸⁸, Oleg O Kirilochev⁸⁹, Andrey Soloviev⁹⁰, Konstantinos N Fountoulakis⁹¹, Alina Wilkowska⁹², Wiesław J Cubała⁹², Muhammad Ayub⁹³, Alzira Silva^{94

95}, Raphael M Bonelli⁹⁶, José M Villagrán-Moreno⁹⁷, Benedicto Crespo-Facorro^{98

99}, Henk Temmingh¹⁰⁰, Eric Decloedt¹⁰¹, Maria R Pedro¹⁰², Hiroyoshi Takeuchi¹⁰³, Masaru Tsukahara¹⁰⁴, Gerhard Gründer¹⁰⁵, Marina Sagud^{106

107}, Andreja Celofiga¹⁰⁸, Dragana Ignjatovic Ristic¹⁰⁹, Bruno B Ortiz¹¹⁰, Helio Elkis¹¹¹, António J Pacheco Palha^{112

113}, Adrián LLerena^{114

115}, Emilio Fernandez-Egea¹¹⁶, Dan Siskind^{117

118}, Abraham Weizman^{119

120}, Rim Masmoudi^{121

122}, Shamin Mohd Saffian¹²³, Jonathan G Leung¹²⁴, Peter F Buckley¹²⁵, Stephen R Marder^{126

127}, Leslie Citrome¹²⁸, Oliver Freudenreich¹²⁹, Christoph U Correll^{6

52

130}, Daniel J Müller^{48

49}

Affiliations

¹ Mental Health Research Center, Eastern State Hospital, Lexington, KY, USA.
² Department of Psychiatry, University of Kentucky, Lexington, KY, USA.
³ Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain.
⁴ Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain.
⁵ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland.
⁶ The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA.
⁷ Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
⁸ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
⁹ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹⁰ Department of Psychiatry, Tampere University Hospital, Tampere, Finland.
¹¹ Department of Psychiatry, Satasairaala, Finland.
¹² National Institute of Mental Health, Klecany, Czech Republic.
¹³ Department of Psychiatry, Charles University, Third Faculty of Medicine, Prague, Czech Republic.
¹⁴ Clinical Pharmacology Unit and Pharmacy Department, Vilardebó Hospital, Administración de Servicios de Salud, Montevideo, Uruguay.
¹⁵ Clinical Pharmacology Unit and Outpatient Clinic, Vilardebó Hospital, Administración de Servicios de Salud, Montevideo, Uruguay.
¹⁶ Universidad de Oviedo. CIBERSAM. INEUROPA. ISPA-FIMBA, Oviedo, Spain.
¹⁷ Hospital Valle del Nalón, Langreo, Spain.
¹⁸ Hospital Universitario Central de Asturias, Oviedo, Spain.
¹⁹ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
²⁰ Laboratory of Clinical Psychopharmacology, Beijing Anding Hospital, Capital Medical University, Beijing, China.
²¹ The National Clinical Research Centre for Mental Disorders & Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
²² Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
²³ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
²⁴ Substance Abuse Treatment Program, Atlanta VA Medical Center, Decatur, Georgia, USA.
²⁵ Department of Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
²⁶ Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
²⁷ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
²⁸ Department of Psychiatry and Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan.
²⁹ Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan.
³⁰ Department of Neuropsychiatry, Nowon Eulji Medical Center, Eulji University, School of Medicine, Seoul, Korea.
³¹ Department of Psychiatry, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
³² Department of Psychiatry, Christian Medical College, Vellore, India.
³³ Institute of Mental Health, Jubilee Campus, University of Nottingham, Triumph Road, Nottingham, United Kingdom.
³⁴ Instituto Nacional de Neurología y Neurocirugía, México City, México.
³⁵ Facultad de Química, Universidad Nacional Autónoma de México (UNAM), México City, México.
³⁶ Department of Physiology, Los Andes University Medical School, Mérida, Venezuela.
³⁷ Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
³⁸ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³⁹ Mental Health Centre Glostrup, Copenhagen University Hospital, Copenhagen, Denmark.
⁴⁰ Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France.
⁴¹ Department of Physical Medicine and Pharmacology, School of Medicine, Universidad de La Laguna, Canary Islands, Spain.
⁴² Hospital Universitario de Canarias, Tenerife, Spain.
⁴³ Department of Internal Medicine, Dermatology and Psychiatry, School of Medicine, and Instituto Universitario de Neurociencia (IUNE), University of La Laguna, Canary Islands, Spain.
⁴⁴ Dutch Clozapine Collaboration Group, Castricum, The Netherlands.
⁴⁵ FACT-team in Heerhugowaard, Department of Severe Mental Illness, Mental Health Services North-Holland North, The Netherlands.
⁴⁶ Mental Health Team Alkmaar, Mental Health Services Noord-Holland-Noord, Alkmaar, The Netherlands.
⁴⁷ Department of Psychiatry, Hacettepe University Faculty of Medicine, Ankara, Turkey.
⁴⁸ Addictions Division, Centre for Addiction and Mental Health, Toronto, Canada.
⁴⁹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁵⁰ Eastern State Hospital, Lexington, Kentucky, USA.
⁵¹ Hazelwood Center, Louisville, Kentucky, USA.
⁵² Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Hempstead, New York, USA.
⁵³ School of Medicine, Keele University, Staffordshire, and Midlands Partnership NHS Foundation Trust, Staffordshire, United Kingdom.
⁵⁴ Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
⁵⁵ Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
⁵⁶ Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Germany.
⁵⁷ Grupo de Investigación en Psiquiatría GIPSI, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia.
⁵⁸ Programa Trastornos del Ánimo, Hospital Universitario San Vicente Fundación, Medellín, Colombia.
⁵⁹ Department of Pharmacy Practice, University of Montana, Missoula, USA.
⁶⁰ Institute of Neuropsychiatry and Addictions (INAD), Parc de Salut Mar, Barcelona, Spain.
⁶¹ Department of Psychiatry, Autonomous University of Barcelona, Spain.
⁶² Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland.
⁶³ Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Switzerland.
⁶⁴ School of Pharmaceutical Sciences, University of Geneva, Switzerland.
⁶⁵ Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Switzerland.
⁶⁶ Department of Psychiatry, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.
⁶⁷ Center for Drug Sciences, Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
⁶⁸ Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, Wellington, New Zealand.
⁶⁹ Department of Psychological Medicine, University of Otago, Wellington, New Zealand.
⁷⁰ Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, and Community Health Sciences University of Calgary, Alberta, Canada.
⁷¹ Faculty of Medicine, University of Montreal, Montreal, Canada.
⁷² Department of Pharmacy, Hôpital du Sacré-Cœur de Montréal, Montreal, Canada.
⁷³ East London NHS Foundation Trust, London, United Kingdom.
⁷⁴ Honorary Clinical Senior Lecturer, Barts and the London School of Medicine, Queen Mary University of London, United Kingdom.
⁷⁵ Department of Psychiatry, School of Medicine, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁷⁶ Department of Psychiatry, Asahi General Hospital, Chiba, Japan.
⁷⁷ National Institute of Mental Health, Neurology and Neurosurgery, Budapest, Hungary.
⁷⁸ Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁷⁹ Secretaría de Salud Mental y Adicciones, Ministerio de Salud de la Provincia de Jujuy, San Salvador de Jujuy, Argentina.
⁸⁰ Instituto Vilapriño, Center for Studies, Assistance and Research in Neurosciences, Mendoza, Argentina.
⁸¹ Department of Psychiatry, LSK Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
⁸² State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR.
⁸³ College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
⁸⁴ Department of Psychiatry, Hamad Medical Corporation, Doha, Qatar.
⁸⁵ NHS, Department of Mental Health, "G. Mazzini" Hospital, Teramo, Italy.
⁸⁶ Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
⁸⁷ British Columbia Mental Health and Substance Use Research Institute, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
⁸⁸ Federal Neuropsychiatric Hospital Yaba, Lagos, Nigeria.
⁸⁹ Department of Clinical Pharmacology, Astrakhan State Medical University, Astrakhan, Russian Federation.
⁹⁰ Department of Psychiatry and Clinical Psychology, Northern State Medical University, Arkhangelsk, Russia.
⁹¹ 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece.
⁹² Department of Psychiatry, Medical University of Gdańsk, Gdańsk, Poland.
⁹³ Department of Psychiatry, Queens University, Kingston, Canada.
⁹⁴ Psychiatry Department, Centro Hospitalar Universitário de S. João, Porto, Portugal.
⁹⁵ Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
⁹⁶ Sigmund Freud University, Vienna, Austria.
⁹⁷ Department of Neurosciences, Jerez University Hospital, Andalusian Health Service, University of Cadiz, Jerez, Spain.
⁹⁸ Department of Psychiatry, School of Medicine, University Hospital Virgen del Rocio-IBIS, Sevilla, Spain.
⁹⁹ Spanish Network for Research in Mental Health (CIBERSAM), Sevilla, Spain.
¹⁰⁰ Department of Psychiatry and Mental Health, University of Cape Town, Valkenberg Hospital, Western Cape, Cape Town, South Africa.
¹⁰¹ Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹⁰² Hospital Central de Maputo, Maputo, Mozambique.
¹⁰³ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
¹⁰⁴ Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan.
¹⁰⁵ Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁰⁶ Department of Psychiatry, School of Medicine, University of Zagreb, Zagreb, Croatia.
¹⁰⁷ Department for Psychiatry and Psychological Medicine, University Hospital Center Zagreb, Croatia.
¹⁰⁸ Department of Psychiatry, University Medical Centre Maribor, Maribor, Slovenia.
¹⁰⁹ University of Kragujevac, Faculty of Medical Sciences, Department of Psychiatry, Kragujevac, Serbia.
¹¹⁰ Group of Resistant Schizophrenia (GER), Schizophrenia Program (Proesq), Federal University of Sao Paulo, SP, Brazil.
¹¹¹ Department and Institute of Psychiatry, University of São Paulo Medical School (FMUSP), Sao Paulo, Brazil.
¹¹² Department and Institute of Psychiatry and Mental Health, Oporto Faculty of Medicine, Oporto, Portugal.
¹¹³ Casa de Salidedo Som Jesus (Psychiatric Hospital), Oporto, Portugal.
¹¹⁴ INUBE Biosanitary Research Institute of Extremadura. Extremadura University Hospital and Medical School, Badajoz, Spain.
¹¹⁵ Spanish Network for Research in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
¹¹⁶ Cambridge Psychosis Centre, Cambrigeshire and Peterborough NHS Foundation Trust & Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
¹¹⁷ Metro South Addiction and Mental Health Service, Brisbane, Australia.
¹¹⁸ Queensland Centre for Mental Health Research and School of Clinical Medicine, University of Queensland, Brisbane, Australia.
¹¹⁹ Research Unit, Geha Mental Health Center and Molecular Psychiatry Laboratory, Felsenstein Medical Research Center, Tel Aviv, Israel.
¹²⁰ Department of Psychiatry Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
¹²¹ Psychiatry "A" Department, Hedi Chaker University Hospital, Sfax, Tunisia.
¹²² Faculty of Medicine, University of Sfax, Sfax, Tunisia.
¹²³ Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
¹²⁴ Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.
¹²⁵ School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
¹²⁶ Semel Institute for Neuroscience at UCLA, Los Angeles, CA, USA.
¹²⁷ VA Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, CA, USA.
¹²⁸ New York Medical College, Department of Psychiatry and Behavioral Sciences, Valhalla, NY, USA.
¹²⁹ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹³⁰ Charité Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Berlin, Germany.

PMID: 34911124
DOI: 10.1055/a-1625-6388

Free article

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

Jose de Leon et al. Pharmacopsychiatry. 2022 Mar.

Free article

. 2022 Mar;55(2):73-86.

doi: 10.1055/a-1625-6388. Epub 2021 Dec 15.

Authors

Affiliations

¹ Mental Health Research Center, Eastern State Hospital, Lexington, KY, USA.
² Department of Psychiatry, University of Kentucky, Lexington, KY, USA.
³ Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain.
⁴ Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain.
⁵ Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland.
⁶ The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA.
⁷ Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
⁸ Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway.
⁹ Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
¹⁰ Department of Psychiatry, Tampere University Hospital, Tampere, Finland.
¹¹ Department of Psychiatry, Satasairaala, Finland.
¹² National Institute of Mental Health, Klecany, Czech Republic.
¹³ Department of Psychiatry, Charles University, Third Faculty of Medicine, Prague, Czech Republic.
¹⁴ Clinical Pharmacology Unit and Pharmacy Department, Vilardebó Hospital, Administración de Servicios de Salud, Montevideo, Uruguay.
¹⁵ Clinical Pharmacology Unit and Outpatient Clinic, Vilardebó Hospital, Administración de Servicios de Salud, Montevideo, Uruguay.
¹⁶ Universidad de Oviedo. CIBERSAM. INEUROPA. ISPA-FIMBA, Oviedo, Spain.
¹⁷ Hospital Valle del Nalón, Langreo, Spain.
¹⁸ Hospital Universitario Central de Asturias, Oviedo, Spain.
¹⁹ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
²⁰ Laboratory of Clinical Psychopharmacology, Beijing Anding Hospital, Capital Medical University, Beijing, China.
²¹ The National Clinical Research Centre for Mental Disorders & Beijing Key Lab of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
²² Department of Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
²³ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
²⁴ Substance Abuse Treatment Program, Atlanta VA Medical Center, Decatur, Georgia, USA.
²⁵ Department of Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
²⁶ Department of Psychiatry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
²⁷ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
²⁸ Department of Psychiatry and Brain Disease Research Center, China Medical University Hospital, Taichung, Taiwan.
²⁹ Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung, Taiwan.
³⁰ Department of Neuropsychiatry, Nowon Eulji Medical Center, Eulji University, School of Medicine, Seoul, Korea.
³¹ Department of Psychiatry, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
³² Department of Psychiatry, Christian Medical College, Vellore, India.
³³ Institute of Mental Health, Jubilee Campus, University of Nottingham, Triumph Road, Nottingham, United Kingdom.
³⁴ Instituto Nacional de Neurología y Neurocirugía, México City, México.
³⁵ Facultad de Química, Universidad Nacional Autónoma de México (UNAM), México City, México.
³⁶ Department of Physiology, Los Andes University Medical School, Mérida, Venezuela.
³⁷ Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
³⁸ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
³⁹ Mental Health Centre Glostrup, Copenhagen University Hospital, Copenhagen, Denmark.
⁴⁰ Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, F-33000 Bordeaux, France.
⁴¹ Department of Physical Medicine and Pharmacology, School of Medicine, Universidad de La Laguna, Canary Islands, Spain.
⁴² Hospital Universitario de Canarias, Tenerife, Spain.
⁴³ Department of Internal Medicine, Dermatology and Psychiatry, School of Medicine, and Instituto Universitario de Neurociencia (IUNE), University of La Laguna, Canary Islands, Spain.
⁴⁴ Dutch Clozapine Collaboration Group, Castricum, The Netherlands.
⁴⁵ FACT-team in Heerhugowaard, Department of Severe Mental Illness, Mental Health Services North-Holland North, The Netherlands.
⁴⁶ Mental Health Team Alkmaar, Mental Health Services Noord-Holland-Noord, Alkmaar, The Netherlands.
⁴⁷ Department of Psychiatry, Hacettepe University Faculty of Medicine, Ankara, Turkey.
⁴⁸ Addictions Division, Centre for Addiction and Mental Health, Toronto, Canada.
⁴⁹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁵⁰ Eastern State Hospital, Lexington, Kentucky, USA.
⁵¹ Hazelwood Center, Louisville, Kentucky, USA.
⁵² Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Hempstead, New York, USA.
⁵³ School of Medicine, Keele University, Staffordshire, and Midlands Partnership NHS Foundation Trust, Staffordshire, United Kingdom.
⁵⁴ Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia.
⁵⁵ Department of Psychiatry, Washington University in St. Louis, St. Louis, Missouri, USA.
⁵⁶ Department of Psychiatry and Psychotherapy, University Medical Center of Mainz, Germany.
⁵⁷ Grupo de Investigación en Psiquiatría GIPSI, Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellin, Colombia.
⁵⁸ Programa Trastornos del Ánimo, Hospital Universitario San Vicente Fundación, Medellín, Colombia.
⁵⁹ Department of Pharmacy Practice, University of Montana, Missoula, USA.
⁶⁰ Institute of Neuropsychiatry and Addictions (INAD), Parc de Salut Mar, Barcelona, Spain.
⁶¹ Department of Psychiatry, Autonomous University of Barcelona, Spain.
⁶² Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for Psychiatric Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland.
⁶³ Center for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Switzerland.
⁶⁴ School of Pharmaceutical Sciences, University of Geneva, Switzerland.
⁶⁵ Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, University of Lausanne, Switzerland.
⁶⁶ Department of Psychiatry, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain.
⁶⁷ Center for Drug Sciences, Faculty of Pharmacy, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
⁶⁸ Te Korowai Whāriki Central Regional Forensic Service, Capital and Coast District Health Board, Wellington, New Zealand.
⁶⁹ Department of Psychological Medicine, University of Otago, Wellington, New Zealand.
⁷⁰ Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, and Community Health Sciences University of Calgary, Alberta, Canada.
⁷¹ Faculty of Medicine, University of Montreal, Montreal, Canada.
⁷² Department of Pharmacy, Hôpital du Sacré-Cœur de Montréal, Montreal, Canada.
⁷³ East London NHS Foundation Trust, London, United Kingdom.
⁷⁴ Honorary Clinical Senior Lecturer, Barts and the London School of Medicine, Queen Mary University of London, United Kingdom.
⁷⁵ Department of Psychiatry, School of Medicine, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
⁷⁶ Department of Psychiatry, Asahi General Hospital, Chiba, Japan.
⁷⁷ National Institute of Mental Health, Neurology and Neurosurgery, Budapest, Hungary.
⁷⁸ Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
⁷⁹ Secretaría de Salud Mental y Adicciones, Ministerio de Salud de la Provincia de Jujuy, San Salvador de Jujuy, Argentina.
⁸⁰ Instituto Vilapriño, Center for Studies, Assistance and Research in Neurosciences, Mendoza, Argentina.
⁸¹ Department of Psychiatry, LSK Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
⁸² State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR.
⁸³ College of Pharmacy, QU Health, Qatar University, Doha, Qatar.
⁸⁴ Department of Psychiatry, Hamad Medical Corporation, Doha, Qatar.
⁸⁵ NHS, Department of Mental Health, "G. Mazzini" Hospital, Teramo, Italy.
⁸⁶ Department of Psychiatry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
⁸⁷ British Columbia Mental Health and Substance Use Research Institute, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
⁸⁸ Federal Neuropsychiatric Hospital Yaba, Lagos, Nigeria.
⁸⁹ Department of Clinical Pharmacology, Astrakhan State Medical University, Astrakhan, Russian Federation.
⁹⁰ Department of Psychiatry and Clinical Psychology, Northern State Medical University, Arkhangelsk, Russia.
⁹¹ 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece.
⁹² Department of Psychiatry, Medical University of Gdańsk, Gdańsk, Poland.
⁹³ Department of Psychiatry, Queens University, Kingston, Canada.
⁹⁴ Psychiatry Department, Centro Hospitalar Universitário de S. João, Porto, Portugal.
⁹⁵ Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
⁹⁶ Sigmund Freud University, Vienna, Austria.
⁹⁷ Department of Neurosciences, Jerez University Hospital, Andalusian Health Service, University of Cadiz, Jerez, Spain.
⁹⁸ Department of Psychiatry, School of Medicine, University Hospital Virgen del Rocio-IBIS, Sevilla, Spain.
⁹⁹ Spanish Network for Research in Mental Health (CIBERSAM), Sevilla, Spain.
¹⁰⁰ Department of Psychiatry and Mental Health, University of Cape Town, Valkenberg Hospital, Western Cape, Cape Town, South Africa.
¹⁰¹ Division of Clinical Pharmacology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
¹⁰² Hospital Central de Maputo, Maputo, Mozambique.
¹⁰³ Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
¹⁰⁴ Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan.
¹⁰⁵ Central Institute of Mental Health, Department of Molecular Neuroimaging, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁰⁶ Department of Psychiatry, School of Medicine, University of Zagreb, Zagreb, Croatia.
¹⁰⁷ Department for Psychiatry and Psychological Medicine, University Hospital Center Zagreb, Croatia.
¹⁰⁸ Department of Psychiatry, University Medical Centre Maribor, Maribor, Slovenia.
¹⁰⁹ University of Kragujevac, Faculty of Medical Sciences, Department of Psychiatry, Kragujevac, Serbia.
¹¹⁰ Group of Resistant Schizophrenia (GER), Schizophrenia Program (Proesq), Federal University of Sao Paulo, SP, Brazil.
¹¹¹ Department and Institute of Psychiatry, University of São Paulo Medical School (FMUSP), Sao Paulo, Brazil.
¹¹² Department and Institute of Psychiatry and Mental Health, Oporto Faculty of Medicine, Oporto, Portugal.
¹¹³ Casa de Salidedo Som Jesus (Psychiatric Hospital), Oporto, Portugal.
¹¹⁴ INUBE Biosanitary Research Institute of Extremadura. Extremadura University Hospital and Medical School, Badajoz, Spain.
¹¹⁵ Spanish Network for Research in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
¹¹⁶ Cambridge Psychosis Centre, Cambrigeshire and Peterborough NHS Foundation Trust & Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
¹¹⁷ Metro South Addiction and Mental Health Service, Brisbane, Australia.
¹¹⁸ Queensland Centre for Mental Health Research and School of Clinical Medicine, University of Queensland, Brisbane, Australia.
¹¹⁹ Research Unit, Geha Mental Health Center and Molecular Psychiatry Laboratory, Felsenstein Medical Research Center, Tel Aviv, Israel.
¹²⁰ Department of Psychiatry Sackler Faculty of Medicine and Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
¹²¹ Psychiatry "A" Department, Hedi Chaker University Hospital, Sfax, Tunisia.
¹²² Faculty of Medicine, University of Sfax, Sfax, Tunisia.
¹²³ Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
¹²⁴ Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.
¹²⁵ School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
¹²⁶ Semel Institute for Neuroscience at UCLA, Los Angeles, CA, USA.
¹²⁷ VA Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, CA, USA.
¹²⁸ New York Medical College, Department of Psychiatry and Behavioral Sciences, Valhalla, NY, USA.
¹²⁹ Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹³⁰ Charité Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Berlin, Germany.

PMID: 34911124
DOI: 10.1055/a-1625-6388

Erratum in

Correction: An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.
de Leon J, Schoretsanitis G, Smith RL, Molden E, Solismaa A, Seppälä N, Kopeček M, Švancer P, Olmos I, Ricciardi C, Iglesias-Garcia C, Iglesias-Alonso A, Spina E, Ruan CJ, Wang CY, Wang G, Tang YL, Lin SK, Lane HY, Kim YS, Kim SH, Rajkumar AP, González-Esquivel DF, Jung-Cook H, Baptista T, Rohde C, Nielsen J, Verdoux H, Quiles C, Sanz EJ, De Las Cuevas C, Cohen D, Schulte PFJ, Ertuğrul A, Anıl Yağcıoğlu AE, Chopra N, McCollum B, Shelton C, Cotes RO, Kaithi AR, Kane JM, Farooq S, Ng CH, Bilbily J, Hiemke C, López-Jaramillo C, McGrane I, Lana F, Eap CB, Arrojo-Romero M, Rădulescu FŞ, Seifritz E, Every-Palmer S, Bousman CA, Bebawi E, Bhattacharya R, Kelly DL, Otsuka Y, Lazary J, Torres R, Yecora A, Motuca M, Chan SKW, Zolezzi M, Ouanes S, De Berardis D, Grover S, Procyshyn RM, Adebayo RA, Kirilochev OO, Soloviev A, Fountoulakis KN, Wilkowska A, Cubała WJ, Ayub M, Silva A, Bonelli RM, Villagrán-Moreno JM, Crespo-Facorro B, Temmingh H, Decloedt E, Pedro MR, Takeuchi H, Tsukahara M, Gründer G, Sagud M, Celofiga A, Ignjatovic Ristic D, Ortiz BB, Elkis H, Pacheco Palha AJ, LLerena A, Fernandez-Egea E, Siskind D, Weizman A, Masmoudi R, Mohd Saffian S, Leung JG, Buckley PF, Marder SR, Citro… See abstract for full author list ➔ de Leon J, et al. Pharmacopsychiatry. 2022 Mar;55(2):e1. doi: 10.1055/a-1737-1527. Epub 2022 Jan 20. Pharmacopsychiatry. 2022. PMID: 35052001 No abstract available.

Abstract

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

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Conflict of interest statement

In the last 3 years, the following authors had no conflict of interest: Drs. de Leon, Schoretsanitis, Molden, Smith, Solismaa, Švancer, Olmos, Ricciardi, Iglesias-Garcia, Iglesias-Alonso, Spina, Ruan, Chuan-Yue Wang, Gang Wang, Tang, Lin, Lane, Rajkumar, González-Esquivel, Jung-Cook, Baptista, Rohde, Nielsen, Verdoux, Quiles, Sanz, De las Cuevas, Cohen, Schulte, Chopra, McCollum, Shelton, Kaithi, Farooq, McGrane, Lana, Arrojo-Romero, Rădulescu, Every-Palmer, Bebawi, Bhattacharya, Otsuka, Lazary, Torres, Yecora, Motuca, Chan, Zolezzi, Ouanes, De Berardis, Grover, Kirilochev, Soloviev, Ayub, Silva, Bonelli, Temmingh, Decloedt, Pedro, Pacheco Palha, LLerena, Fernandez-Egea, Siskind, Masmoudi, Mohd Saffian, Leung and Buckley. In the last 3 years several authors report conflicts of interests. Dr. Seppälä is permanent medical advisor, received lecture fees and is an advisory board member from Viatris that markets clozapine in Finland and other European countries. Dr. Kopeček participated in speakers/advisory boards and lectured with the support of Angelini, Janssen Pharmaceuticals, Lundbeck and Richter Gedeon. Dr. Yong Sik Kim received grants, research support and honoraria from Janssen, Otsuka, Whan in Pharm and Bukwang Pharm (Sumitomo Dannipon Pharma). Dr. Se Hyun Kim received research grants from and/or served as a lecturer for Janssen, Eli Lilly, and Dongwha. Dr. Ertuğrul has received speaker’s honoraria from Abdi İbrahim Otsuka. Dr. Anıl Yağcıoğlu has received speaker’s honoraria and consulting fees from Janssen and Abdi İbrahim Otsuka. Dr. Cotes has received research funding from Otsuka, Lundbeck, Roche, Alkermes, and is a consultant for Saladax Biomedical. Dr. Kane reports personal fees from Alkermes, personal fees from Allergan, personal fees from Bristol-Myers Squibb, personal fees from IntraCellular Therapies, Janssen, Lundbeck, Minerva, Neurocrine, Otsuka, Pierre Fabre, Reviva, Sunovion, Takeda, Teva, outside-the-submitted work from LB Pharma, MedAvante and The Vanguard Research Group. Dr. Ng had served as consultant for Grunbiotics, Lundbeck, Servier, and Janssen-Cilag, and received research speaker honoraria from Servier, Janssen-Cilag and Pfizer.IMcG received royalties from Hogrefe Publishing Corp. T.L. Dr. Bilbily is supported by the National Institute on Drug Abuse training grant 5T32DA007261-30 (MPI). Dr. Hiemke received speaker’s honoraria from Otsuka. Dr. López-Jaramillo reports financial support for research from Financial support from the National Institute of Mental Health, USA, MinCiencias, Colombia and the Universidad de Antioquia, Colombia. Dr. Eap received honoraria for conferences or teaching CME courses from Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Vifor-Pharma, and Zeller. Dr. Seifritz has received honoraria from Schwabe GmbH for educational lectures. He has further received educational grants and consulting fees from Janssen Cilag, Lundbeck, Angelini, Otsuka, Servier, Recordati, Vifor, Sunovion, and Mepha. Dr. Bousman is a member of the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Pharmacogene Variation Consortium (PharmVar). Dr. Kelly has served as a consultant for Alkermes, Lyndra and Sunovion. Dr. Procyshyn has been on the speaker's bureau and attended advisory board meetings for Janssen, Lundbeck, and Otsuka. Dr. Adebayo was on the advisory board of Janssen for a Long Acting Injectable Paliperidone palmitate in Nigeria. Janssen is not involved in Clozapine in Nigeria. Dr. Fountoulakis has received grants in the past, served as 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. Since January 2020 he has been the director of Cochrane Greece and completely free from any conflict of interest. Dr. Wilkowska has received research support from Angelini, Biogen, Eli Lilly and Company, Janssen-Cilag, Lundbeck, Polpharma, Sanofi and Valeant. Dr. Cubała has received research support from Alkermes, Allergan, Auspex, Biogen, Celon, Ferrier, Forest Laboratories, Janssen, Otsuka, and Sanofi; he has served on speaker bureaus for Angelini, Celon, Janssen, and Sanofi, and he has served as a consultant for GW Pharmaceuticals, Janssen, Celon and Sanofi. Dr. Villagrán-Moreno has received speakerʼs honoraria from Janssen and have developed lectures and presented clozapine lectures for Adamed, which sells clozapine in Spain; he has participated in advisory boards for Rovi and in research projects for Otsuka. Dr. Crespo-Facorro has received funding unrelated to the present work for research projects and/or honoraria as a consultant or speaker from the following entities: Angelini, Janssen-Cilag, Lundbeck, Otsuka, Mylan, Sanofi-Aventis, ADAMED, Agencia Española de Investigacion, Instituto de Salud Carlos III, the EU Seventh Framework Program and Horizon 2020. Dr. Takeuchi has received speaker’s fees from EA Pharma, Kyowa, Janssen, Lundbeck, Meiji Seika Pharma, Mochida, Otsuka, Sumitomo Dainippon Pharma, Takeda, and Yoshitomiyakuhin. Dr. Tsukahara has received speaker's honoraria from Eisai Inc. Dr. Gründer has served as a consultant for Allergan (Dublin, Ireland), Boehringer Ingelheim (Ingelheim, Germany), Institute for Quality and Efficiency in Health Care (IQWiG, Cologne, Germany), Janssen-Cilag (Neuss, Germany), Lundbeck (Copenhagen, Denmark), Otsuka (Chiyoda, Japan), Recordati (Milan, Italy), Sage (Cambridge, USA), and Takeda (Osaka, Japan). He has served on the speakers’ bureau of Gedeon Richter (Budapest, Hungary), Janssen Cilag, Lundbeck, Otsuka, Recordati. He has received grant support from Boehringer Ingelheim, Lundbeck and Saladax (Bethlehem, USA). He is co-founder and/or shareholder of Mind and Brain Institute GmbH (Zornheim, Germany), Brainfoods GmbH (Zornheim, Germany), OVID Health Systems GmbH (Berlin, Germany) and MIND Foundation gGmbH (Berlin, Germany). Dr. Sagud participated in lectures for the following companies: Alkaloid, Belupo, Elli Lilly, Gedeon Richter, Jadran Galenski Laboratorij, Johnson / Johnson, Lundbeck, Makpharm, Pliva, Stada and participated in the clinical trial: Eli Lilly, Krka and Gedeon Richter. Dr. Celofiga received speaker’s honoraria from Ely Lilly, Lundbeck, Richter Gedeon, Krka, Lek, Pliva, Angelini Pharma and participated in advisory boards for Janssen Pharmaceuticals and Lundbeck. Dr. Ignjatovic Ristic developed and presented clozapine lectures with the support of Mylan, received speakerʼs honoraria from Mylan, Teva Serbia, Pharm Swiss, Krka and Janssen. Dr. Ortiz has been a consultant and has received honoraria from Janssen-Cilag. Dr. Elkis received research grants from the São Paulo Research Support Foundation (FAPESP) and honoraria for participation as a member of advisory boards, speaker, or travel support from the following pharmaceutical companies: Aché, Cristalia, Daiichi-Sankyo, Janssen, Mantecorp-Hypera, Sandoz, and Teva. Dr. Weizman received speakerʼs honoraria from Lundbeck, Lilly, Teva, Trima, Jansen, Medison, Novartis and AstraZeneca. These activities were unrelated to the current study. Dr Marder reports consultation fees from Roche, Sunovion, Merck, Boehringer Ingelheim and Otsuka. He reports research support from Boehringer-Ingelheim, and GW Pharma. Dr. Citrome has engaged in collaborative research with, or received consulting or speaking fees, from: AbbVie, Acadia, Alexza, Alkermes, Allergan, Angelini, Astellas, AstraZeneca, Avanir, Axsome, BioXcel, Boehringer Ingelheim, Bristol-Myers Squibb, Cadent Therapeutics, Eisai, Eli Lilly, Forum, Genentech, Impel, Indivior, Intra-Cellular Therapies, Janssen, Jazz, Karuna, Lundbeck, Luye, Lyndra, Medavante-Prophase, Meiji, Merck, Medivation, Mylan, Neurocrine, NeuroRx, Novartis, Noven, Osmotica, Otsuka, Pfizer, Reckitt Benckiser, Relmada, Reviva, Sage, Shire, Sunovion, Takeda, Teva, University of Arizona, Valeant, Vanda, and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research. Dr. Freudenreich has the following financial relationship with a commercial interest to disclose (recipient SELF; content area SCHIZOPHRENIA): Alkermes – Research grant (to institution), consultant honoraria (Advisory Board); Avanir – Research grant (to institution); Janssen – Research grant (to institution), consultant honoraria (Advisory Board); Integral - Consultant honoraria; Neurocrine – Consultant honoraria (Advisory Board); Novartis – Consultant honoraria; Otsuka – Research grant (to institution); Roche – Consultant honoraria; Springer Verlag – Royalties (medical writer); Elsevier – Honoraria (medical editing); Global Medical Education – Honoraria (CME speaker and content developer); Medscape – Honoraria (CME speaker); American Psychiatric Association – Consultant honoraria (SMI Adviser); Wolters-Kluwer – Royalties (content developer); UpToDate – Royalties, honoraria (content developer and editor, including for a chapter on clozapine). Dr. Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Damitsa, Gedeon Richter, Hikma, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of LB Pharma. Dr. Müller reports he has been a co-investigator for two pharmacogenetic studies where genetic test kits were provided as an in-kind contribution by Myriad Neuroscience. He did not receive any payments or any equity, stocks, or options from any pharmacogenetic companies. He is also a co-inventor of two patents assessing risk for antipsychotic-induced weight gain (pending).

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An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

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An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

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