title: Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment.
abstract: OBJECTIVE
  A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD.
  
  
  METHODS
  After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs.
  
  
  RESULTS
  Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects.
  
  
  CONCLUSIONS
  There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.
authors.forename: Shweta
authors.initials: S
authors.lastname: Anand
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.|School of Health Science, Macao Polytechnic Institute, Macao SAR, China.
authors.forename: Henry
authors.initials: H
authors.lastname: Tong
authors.affiliation: East London NHS Foundation Trust, Bedfordshire, Institute of Psychiatry, Psychology and Neuroscience, London, UK.|Research Department of Practice and Policy, School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: Frank M C
authors.initials: FMC
authors.lastname: Besag
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Chan
authors.affiliation: Department of Psychology, Developmental Brain-Behaviour Laboratory, Department of Psychology, University of Southampton, Southampton, UK.|The Child Study Center at NYU Langone Medical Center, New York, NY, USA.
authors.forename: Samuele
authors.initials: S
authors.lastname: Cortese
authors.affiliation: Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong. i.wong@ucl.ac.uk.|Research Department of Practice and Policy, School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK. i.wong@ucl.ac.uk.
authors.forename: Ian C K
authors.initials: ICK
authors.lastname: Wong
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002648:Child; D003000:Clonidine / Q000627:therapeutic use; D000069582:Eszopiclone / Q000627:therapeutic use; D005971:Glutamates / Q000627:therapeutic use; D016316:Guanfacine / Q000627:therapeutic use; D006801:Humans; D008550:Melatonin / Q000627:therapeutic use; D064887:Observational Studies as Topic; D011725:Pyridines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000077334:Zolpidem
chemical_list: D005971:Glutamates; D011725:Pyridines; D016316:Guanfacine; D000077334:Zolpidem; C026166:theanine; D008550:Melatonin; D003000:Clonidine; D000069582:Eszopiclone