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Neurosci Biobehav Rev. 2019 Sep 20. pii: S0149-7634(19)30235-0. doi: 10.1016/j.neubiorev.2019.09.023. [Epub ahead of print]

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

Author information

1
Section Child Neuropsychology, Department of Child Psychiatry, University Hospital of the RWTH Aachen University, 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
Department 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
Nottingham China Health China Institute, University of Nottingham, Ningbo, China.
21
Section Child Neuropsychology, Department of Child Psychiatry, University Hospital of the RWTH Aachen University, Aachen, Germany; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Forschungszentrum Jülich GmbH and RWTH Aachen University, Germany.
22
Division of Psychiatry & Applied Psychology, School of Medicine, Institute of Mental Health, University of Nottingham, UK. Electronic address: Elizabeth.Liddle@nottingham.ac.uk.

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; Long-term methylphenidate treatment; adverse neuropsychiatric events; anxiety; bipolar; mood; psychosis; seizures; sleep disorders; substance use disorder; suicidal ideation; tics

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