학술논문
The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project.
Document Type
Academic Journal
Author
Carucci S; University of Cagliari, Italy.; ASL Cagliari, Italy.; Zuddas A; University of Cagliari, Italy.; ASL Cagliari, Italy.; Lampis A; University College London, UK.; Man KKC; Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.; Hong Kong Science Park, China.; University College London Hospitals NHS Foundation Trust, UK.; The University of Hong Kong, China.; Balia C; University of Cagliari, Italy.; ASL Cagliari, Italy.; Buitelaar J; Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands.; Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.; Danckaerts M; University Psychiatric Center KU Leuven, Belgium.; Dittmann RW; University of Heidelberg, Mannheim, Germany.; Donno F; University of Cagliari, Italy.; Falissard B; Université Paris-Saclay, France.; Gagliano A; University of Messina, Italy.; Garas P; Semmelweis University, Budapest, Hungary.; Häge A; University of Heidelberg, Mannheim, Germany.; Hollis C; University of Nottingham, UK.; Inglis SK; University of Dundee, UK.; Konrad K; University Hospital RWTH Aachen, Germany.; RWTH Aachen and Research Centre Jülich, Germany.; Kovshoff H; University of Southampton, UK.; Liddle E; University of Nottingham, UK.; McCarthy S; University College Cork, Ireland.; Neubert A; Universitätsklinikum Erlangen, Germany.; Nagy P; Bethesda Children's Hospital, Budapest, Hungary.; Rosenthal E; Evelina London Children's Hospital, UK.; Sonuga-Barke EJS; King's College London, UK.; Wong ICK; University College London, UK.; Hong Kong Science Park, China.; University College London Hospitals NHS Foundation Trust, UK.; The University of Hong Kong, China.; Aston University, Birmingham, UK.; Banaschewski T; University of Heidelberg, Mannheim, Germany.; Coghill D; University of Dundee, UK.; University of Melbourne, VIC, Australia.
Source
Publisher: SAGE Publications Country of Publication: United States NLM ID: 9615686 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-1246 (Electronic) Linking ISSN: 10870547 NLM ISO Abbreviation: J Atten Disord Subsets: MEDLINE
Subject
Language
English
Abstract
Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age.
Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.
Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.
Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SC reports collaboration on projects from the EU Seventh Framework Program and on clinical trials sponsored by Lundbeck, Otsuka, Janssen-Cilag, Angelini and Acadia. KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. CB reports collaboration on projects from the EU Seventh Framework Program and on clinical trials sponsored by Otsuka, Janssen-Cilag, Angelini and Acadia. JB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Medice, Angelini, Janssen, Boehringer-Ingelheim, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. MD has received research funding from Takeda–Shire, outside the submitted work. RWD—For the past 3 years, he has no conflicts of interest to report. As a former company employee, he has been a stockholder of Eli Lilly & Co. FD reports collaboration as sub-investigator in clinical trials sponsored by Lundbeck as an independent rater in clinical trials sponsored by Servier and Acadia. BF has been a consultant or speaker for Abbvie, Actelion, Allergan, Almirall, Alnylam, Amgen, Astellas, Astrazeneca, Bayer, Biogen, Biopecs, Bioproject, Biotronik, BMS,Boehringer, Celgène, Daiichi-Sankyio, Ethypharm, Forestlab, Genevrier, Genzyme, Gilead, Grünenthal, GSK, Idorsia, IMS, Indivior, IQVIA, JNJ, Léo, Lilly, Lundbeck, Menarini, MSD, Novartis, Novonordisk, Otsuka, Pfizer, Pierre-Frabre, Recordati, Roche, SANOFI, Servier, Takeda, UCB, ViiV, and Wellmera. AH has received compensation for serving as consultant or speaker for Shire–Takeda and Medice, unrelated to this work. KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. CH reports research funding from the NIHR including the Health Technology Assessment SATURN trial (grant ref: NIHR128472) comparing methylpheidate with guanfacine for children and young people with ADHD and tics. CH was chair of the NICE Guideline (CG155) for psychosis and schizophrenia in children and young people; member of the NICE ADHD Guideline Update committee (NG87) and is a member of Eunethydis and the Europhean ADHD Guideline Group. SM reports speaker’s fee, travel support, and research support from Shire, outside the submitted work. AN reports research funding from the EU, the German Ministry of Health, and the German Federal Joint Committee, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker’s fee and travel support from Shire, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker’s fee and travel support from Shire, outside the submitted work. ESB has received in the last 3 years speakers fees from Takeda and Medice and research support from QBTech. AZ served in an advisory or consultancy role for Angelini, EduPharma, Servier; received conference support or speaker’s fee from Angelini and Janssen; participated in clinical trials conducted by Angelini, Janssen, Lundbeck, Otsuka, Roche, Sevier, and Shire; and received royalties from Giunti OS and Oxford University Press. ICKW reports research and educational funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the Hong Kong Innovation and Technology Commission, the NIHR, the EU, and the Australian National Health and Medical Research Council, and the expert testimony payment from the Hong Kong Court of Final Appeal; outside the submitted work. TB served in an advisory or consultancy role for eye level, Infectopharm, Medice, Neurim Pharmaceuticals, Oberberg GmbH and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. DC reports, in the past 3 years, a consultant, member of advisory board, or speaker role for Takeda–Shire, Medice, Novartis, and Servier. He has received royalties from Oxford University Press and Cambridge University Press; research support from the Australian National Health and Medical Research Council and the Royal Children’s Hospital Foundation; and funding for the current study from the European Commission. All other authors declare no competing interests.
Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age.
Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable.
Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.
Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SC reports collaboration on projects from the EU Seventh Framework Program and on clinical trials sponsored by Lundbeck, Otsuka, Janssen-Cilag, Angelini and Acadia. KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. CB reports collaboration on projects from the EU Seventh Framework Program and on clinical trials sponsored by Otsuka, Janssen-Cilag, Angelini and Acadia. JB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Medice, Angelini, Janssen, Boehringer-Ingelheim, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. MD has received research funding from Takeda–Shire, outside the submitted work. RWD—For the past 3 years, he has no conflicts of interest to report. As a former company employee, he has been a stockholder of Eli Lilly & Co. FD reports collaboration as sub-investigator in clinical trials sponsored by Lundbeck as an independent rater in clinical trials sponsored by Servier and Acadia. BF has been a consultant or speaker for Abbvie, Actelion, Allergan, Almirall, Alnylam, Amgen, Astellas, Astrazeneca, Bayer, Biogen, Biopecs, Bioproject, Biotronik, BMS,Boehringer, Celgène, Daiichi-Sankyio, Ethypharm, Forestlab, Genevrier, Genzyme, Gilead, Grünenthal, GSK, Idorsia, IMS, Indivior, IQVIA, JNJ, Léo, Lilly, Lundbeck, Menarini, MSD, Novartis, Novonordisk, Otsuka, Pfizer, Pierre-Frabre, Recordati, Roche, SANOFI, Servier, Takeda, UCB, ViiV, and Wellmera. AH has received compensation for serving as consultant or speaker for Shire–Takeda and Medice, unrelated to this work. KKCM reports grants from the CW Maplethorpe Fellowship, the UK National Institute for Health and Care Research (NIHR), the EU Horizon 2020 Framework, and the Hong Kong Research Grant Council, and personal fees from IQVIA Holdings, outside the submitted work. CH reports research funding from the NIHR including the Health Technology Assessment SATURN trial (grant ref: NIHR128472) comparing methylpheidate with guanfacine for children and young people with ADHD and tics. CH was chair of the NICE Guideline (CG155) for psychosis and schizophrenia in children and young people; member of the NICE ADHD Guideline Update committee (NG87) and is a member of Eunethydis and the Europhean ADHD Guideline Group. SM reports speaker’s fee, travel support, and research support from Shire, outside the submitted work. AN reports research funding from the EU, the German Ministry of Health, and the German Federal Joint Committee, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker’s fee and travel support from Shire, outside the submitted work. PN has been a consultant or speaker for Medice, Servier, and Egis Pharmaceuticals, outside the submitted work. ER received speaker’s fee and travel support from Shire, outside the submitted work. ESB has received in the last 3 years speakers fees from Takeda and Medice and research support from QBTech. AZ served in an advisory or consultancy role for Angelini, EduPharma, Servier; received conference support or speaker’s fee from Angelini and Janssen; participated in clinical trials conducted by Angelini, Janssen, Lundbeck, Otsuka, Roche, Sevier, and Shire; and received royalties from Giunti OS and Oxford University Press. ICKW reports research and educational funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the Hong Kong Innovation and Technology Commission, the NIHR, the EU, and the Australian National Health and Medical Research Council, and the expert testimony payment from the Hong Kong Court of Final Appeal; outside the submitted work. TB served in an advisory or consultancy role for eye level, Infectopharm, Medice, Neurim Pharmaceuticals, Oberberg GmbH and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. DC reports, in the past 3 years, a consultant, member of advisory board, or speaker role for Takeda–Shire, Medice, Novartis, and Servier. He has received royalties from Oxford University Press and Cambridge University Press; research support from the Australian National Health and Medical Research Council and the Royal Children’s Hospital Foundation; and funding for the current study from the European Commission. All other authors declare no competing interests.