title: Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles.
  
  
  
  We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings.
  
  
  
  No ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and possibly presented at relevant national and international conferences.
  
  
  
  CRD42014008976.
authors.affiliation: Department of Psychology, Developmental Brain-Behaviour Laboratory, Academic Unit of Psychology, Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, and Solent NHS Trust, Southampton, UK.|New York University Child Study Center, New York City, New York, USA.
authors.forename: Samuele
authors.initials: S
authors.lastname: Cortese
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Adamo
authors.affiliation: Research Unit of Child and Adolescent Psychiatry, Aalborg Psychiatric Hospital, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Mohr-Jensen
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.|Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Hayes
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.|Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
authors.forename: Sahar
authors.initials: S
authors.lastname: Bhatti
authors.affiliation: Child and Adolescent Neuropsychiatric Unit, 'A. Cao' Paediatric Hospital, 'G. Brotzu' Hospital Trust, Cagliari, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Carucci
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Del Giovane
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.|Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
authors.forename: Lauren Z
authors.initials: LZ
authors.lastname: Atkinson
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Medical Faculty, Central Institute of Mental Health, Mannheim/Heidelberg University, Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Institute of Psychiatry, Psychology and Neurosciences, King's College London, and the Maudsley Hospital, London, UK.
authors.forename: Emily
authors.initials: E
authors.lastname: Simonoff
authors.affiliation: Child and Adolescent Neuropsychiatric Unit, 'A. Cao' Paediatric Hospital, 'G. Brotzu' Hospital Trust, Cagliari, Italy.|Child and Adolescent Neuropsychiatry Unit, University of Cagliari, Cagliari, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zuddas
authors.affiliation: Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, University of Verona, Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
authors.affiliation: Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, University of Verona, Verona, Italy.|Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA.
authors.forename: Marianna
authors.initials: M
authors.lastname: Purgato
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychiatric University Clinic Zurich, Switzerland.|Department of Clinical Psychology and Epidemiology, Psychology, University of Basel, Basel, Switzerland.|Department of Capital Region Psychiatry, Child and Adolescent Mental Health Centre, Copenhagen, Denmark.
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Steinhausen
authors.affiliation: Cochrane Schizophrenia Group, Institute of Mental Health, a Partnership between the University of Nottingham and Nottinghamshire Healthcare NHS Trust, UK.
authors.forename: Farhad
authors.initials: F
authors.lastname: Shokraneh
authors.affiliation: Cochrane Schizophrenia Group, Institute of Mental Health, a Partnership between the University of Nottingham and Nottinghamshire Healthcare NHS Trust, UK.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.|Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
authors.forename: Andrea
authors.identifier: 0000-0001-5179-8321
authors.initials: A
authors.lastname: Cipriani
authors.affiliation: Division of Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.|Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.|Department of Psychiatry, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Coghill
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D006801:Humans; D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D016642:Bupropion / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D003000:Clonidine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D008774:Methylphenidate / Q000627:therapeutic use; D000071076:Network Meta-Analysis as Topic; D016896:Treatment Outcome; D000078202:Systematic Reviews as Topic
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016642:Bupropion; D000697:Central Nervous System Stimulants; D003000:Clonidine; D008774:Methylphenidate
keywords: Attention-Deficit/Hyperactivity Disorder; acute treatment; network meta-analysis; pharmacological treatment; systematic review