Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis

Sara Carucci; Carla Balia; Antonella Gagliano; Angelico Lampis; Jan K Buitelaar; Marina Danckaerts; Ralf W Dittmann; Peter Garas; Chris Hollis; Sarah Inglis; Kerstin Konrad; Hanna Kovshoff; Elizabeth B Liddle; Suzanne McCarthy; Peter Nagy; Pietro Panei; Roberta Romaniello; Tatiana Usala; Ian C K Wong; Tobias Banaschewski; Edmund Sonuga-Barke; David Coghill; Alessandro Zuddas; ADDUCE Consortium

doi:10.1016/j.neubiorev.2020.09.031

Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis

Neurosci Biobehav Rev. 2021 Jan:120:509-525. doi: 10.1016/j.neubiorev.2020.09.031. Epub 2020 Oct 17.

Authors

Sara Carucci¹, Carla Balia², Antonella Gagliano², Angelico Lampis³, Jan K Buitelaar⁴, Marina Danckaerts⁵, Ralf W Dittmann⁶, Peter Garas⁷, Chris Hollis⁸, Sarah Inglis⁹, Kerstin Konrad¹⁰, Hanna Kovshoff¹¹, Elizabeth B Liddle¹², Suzanne McCarthy¹³, Peter Nagy¹⁴, Pietro Panei¹⁵, Roberta Romaniello¹⁶, Tatiana Usala¹⁷, Ian C K Wong¹⁸, Tobias Banaschewski⁶, Edmund Sonuga-Barke¹⁹, David Coghill²⁰, Alessandro Zuddas²; ADDUCE Consortium

Affiliations

¹ Department of Biomedical Sciences, Section Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; Child and Adolescent Neuropsychiatry, "A. Cao'' Paediatric Hospital, "G. Brotzu" Hospital Trust, Via E. Jenner, 09121 Cagliari, Italy. Electronic address: sara.carucci@gmail.com.
² Department of Biomedical Sciences, Section Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; Child and Adolescent Neuropsychiatry, "A. Cao'' Paediatric Hospital, "G. Brotzu" Hospital Trust, Via E. Jenner, 09121 Cagliari, Italy.
³ Paediatric Endocrinology Unit, A. Cao" Pediatric Hospital, Brotzu Hospital Trust, Cagliari, Italy.
⁴ Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre, & Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, the Netherlands.
⁵ Department of Child and Adolescent Psychiatry, University Psychiatric Center, Leuven, KU, Belgium; Department of Neurosciences, University Psychiatric Center, Leuven, KU, Belgium.
⁶ Paediatric Psychopharmacology, Department of Child & Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
⁷ Semmelweis University Mental Health Sciences School of PhD Studies, Budapest, Hungary.
⁸ Division of Psychiatry & Applied Psychology, School of Medicine, Institute of Mental Health, University of Nottingham, UK; NIHR MindTech Medtech Co-operative, Institute of Mental Health, University of Nottingham, Nottingham, UK; NIHR Nottingham Biomedical Research Centre, Institute of Mental Health, University of Nottingham, Nottingham, UK.
⁹ Tayside Clinical Trials Unit, University of Dundee, Dundee, UK.
¹⁰ Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Faculty of Medicine, RWTH Aachen University, Aachen, Germany; JARA-Brain Institute II, Molecular Neuroscience and Neuroimaging, Research Center Jülich, Jülich, Germany.
¹¹ School of Psychology, University of Southampton, Southampton, UK.
¹² Division of Psychiatry & Applied Psychology, School of Medicine, Institute of Mental Health, University of Nottingham, UK.
¹³ School of Pharmacy, University College Cork, Cork, Ireland.
¹⁴ Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary.
¹⁵ Grant Office and Technology Transfer, Istituto Superiore di Sanità, Rome, Italy.
¹⁶ Department of Biomedical Sciences, Section Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
¹⁷ Child and Adolescent Neuropsychiatry Unit, Azienda per la Tutela della Salute, ATS Sardegna, ASSL Oristano, Italy.
¹⁸ Centre for Paediatric Pharmacy Research, Research Department of Practice and Policy, UCL School of Pharmacy, London, UK; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong.
¹⁹ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK; Department of Child & Adolescent Psychiatry, Aarhus University, Denmark.
²⁰ Departments of Paediatrics and Psychiatry, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia; Division of Neuroscience, School of Medicine, University of Dundee, Dundee, UK.

PMID: 33080250
DOI: 10.1016/j.neubiorev.2020.09.031

Abstract

Background: Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth.

Objectives: To systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty.

Results: Eighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited.

Conclusions: Long-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators.

Keywords: Attention deficit/hyperactivity disorder (ADHD); growth; height; methylphenidate; puberty; stimulants; weight.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Adolescent
Attention Deficit Disorder with Hyperactivity* / drug therapy
Body Weight
Central Nervous System Stimulants* / therapeutic use
Child
Humans
Methylphenidate* / therapeutic use
Prospective Studies
Treatment Outcome

Substances

Central Nervous System Stimulants
Methylphenidate