Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence

Helga Krinzinger; Charlotte L Hall; Madeleine J Groom; Mohammed T Ansari; Tobias Banaschewski; Jan K Buitelaar; Sara Carucci; David Coghill; Marina Danckaerts; Ralf W Dittmann; Bruno Falissard; Peter Garas; Sarah K Inglis; Hanna Kovshoff; Puja Kochhar; Suzanne McCarthy; Peter Nagy; Antje Neubert; Samantha Roberts; Kapil Sayal; Edmund Sonuga-Barke; Ian C K Wong; Jun Xia; Alessandro Zuddas; Chris Hollis; Kerstin Konrad; Elizabeth B Liddle; ADDUCE Consortium

doi:10.1016/j.neubiorev.2019.09.023

Neurological and psychiatric adverse effects of long-term methylphenidate treatment in ADHD: A map of the current evidence

Neurosci Biobehav Rev. 2019 Dec:107:945-968. doi: 10.1016/j.neubiorev.2019.09.023. Epub 2019 Sep 20.

Authors

Helga Krinzinger¹, Charlotte L Hall², Madeleine J Groom², Mohammed T Ansari³, Tobias Banaschewski⁴, Jan K Buitelaar⁵, Sara Carucci⁶, David Coghill⁷, Marina Danckaerts⁸, Ralf W Dittmann⁹, Bruno Falissard¹⁰, Peter Garas¹¹, Sarah K Inglis¹², Hanna Kovshoff¹³, Puja Kochhar², Suzanne McCarthy¹⁴, Peter Nagy¹⁵, Antje Neubert¹⁶, Samantha Roberts¹⁷, Kapil Sayal², Edmund Sonuga-Barke¹⁸, Ian C K Wong¹⁹, Jun Xia²⁰, Alessandro Zuddas⁶, Chris Hollis²¹, Kerstin Konrad²², Elizabeth B Liddle²³; ADDUCE Consortium

Affiliations

¹ Section Child Neuropsychology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, RWTH Aachen, Germany.
² Division of Psychiatry & Applied Psychology, School of Medicine, Institute of Mental Health, University of Nottingham, UK.
³ School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Canada.
⁴ Department of Child & Adolescent Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
⁵ 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.
⁶ Child and Adolescent Neuropsychiatry Unit, Department of Biomedical Science, University of Cagliari & "A. Cao" Pediatric Hospital, Brotzu Hospital Trust, Cagliari, Italy.
⁷ 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.
⁸ Department of Child and Adolescent Psychiatry, University Psychiatric Center, Leuven, KU, Belgium; Department of Neurosciences, University Psychiatric Center, Leuven, KU, Belgium.
⁹ Paediatric Psychopharmacology, Department of Child & Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
¹⁰ University Paris-Sud, Univ. Paris-Descartes, AP-HP, INSERM U1178, Paris, France.
¹¹ Semmelweis University, Károly Rácz School of PhD Studies, Mental Health Sciences Phd School, Budapest, Hungary.
¹² Tayside Clinical Trials Unit, University of Dundee, Dundee, UK.
¹³ School of Psychology, University of Southampton, Southampton, UK.
¹⁴ School of Pharmacy, University College Cork, Cork, Ireland.
¹⁵ Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary.
¹⁶ Department of Paediatrics and Adolescents Medicine, University Hospital Erlangen, Erlangen, Germany.
¹⁷ Nottinghamshire Healthcare NHS Foundation Trust, UK.
¹⁸ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK; Department of Experimental Clinical & Health Psychology, Ghent University, Ghent, Belgium.
¹⁹ 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.
²⁰ The Nottingham Ningbo GRADE Center, Nottingham China Health Institute, The University of Nottingham Ningbo, China.
²¹ Division of Psychiatry & Applied Psychology, School of Medicine, Institute of Mental Health, University of Nottingham, UK; National Institute of Health Research (NIHR) MindTech MedTech Cooperative, Nottingham, UK; NIHR Nottingham Biomedical Research Centre, Nottingham, UK.
²² Section Child Neuropsychology, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital, RWTH Aachen, Germany; JARA-BRAIN Institute II, Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, Germany.
²³ Division of Psychiatry & Applied Psychology, School of Medicine, Institute of Mental Health, University of Nottingham, UK. Electronic address: Elizabeth.Liddle@nottingham.ac.uk.

PMID: 31545988
DOI: 10.1016/j.neubiorev.2019.09.023

Abstract

Methylphenidate (MPH), the most common medication for children with Attention Deficit/Hyperactivity Disorder (ADHD) in many countries, is often prescribed for long periods of time. Any long-term psychotropic treatment in childhood raises concerns about possible adverse neurological and psychiatric outcomes. We aimed to map current evidence regarding neurological and psychiatric outcomes, adverse or beneficial, of long-term MPH (> 1 year) treatment in ADHD. We coded studies using a "traffic light" system: Green: safe/favours MPH; Amber: warrants caution; Red: not safe/not well-tolerated. Un-categorisable study findings were coded as "Unclear". Although some evidence suggests an elevated risk of psychosis and tics, case reports describe remission on discontinuation. Several studies suggest that long-term MPH may reduce depression and suicide in ADHD. Evidence suggests caution in specific groups including pre-school children, those with tics, and adolescents at risk for substance misuse. We identified a need for more studies that make use of large longitudinal databases, focus on specific neuropsychiatric outcomes, and compare outcomes from long-term MPH treatment with outcomes following shorter or no pharmacological intervention.

Keywords: ADHD; Adverse neuropsychiatric events; Anxiety; Bipolar; Long-term methylphenidate treatment; Mood; Psychosis; Seizures; Sleep disorders; Substance use disorder; Suicidal ideation; Tics.

Publication types

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

MeSH terms

Attention Deficit Disorder with Hyperactivity / drug therapy*
Brain Diseases / chemically induced
Central Nervous System Stimulants / adverse effects*
Central Nervous System Stimulants / therapeutic use
Humans
Mental Disorders / chemically induced
Methylphenidate / adverse effects*
Methylphenidate / therapeutic use
Time Factors

Substances

Central Nervous System Stimulants
Methylphenidate