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Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment

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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.

Conclusion

There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Shweta Anand, Henry Tong, Esther W. Chan & Ian C. K. Wong

  2. School of Health Science, Macao Polytechnic Institute, Macao SAR, China

    Henry Tong

  3. East London NHS Foundation Trust, Bedfordshire, Institute of Psychiatry, Psychology and Neuroscience, London, UK

    Frank M. C. Besag

  4. Department of Psychology, Developmental Brain-Behaviour Laboratory, Department of Psychology, University of Southampton, Southampton, UK

    Samuele Cortese

  5. The Child Study Center at NYU Langone Medical Center, New York, NY, USA

    Samuele Cortese

  6. Research Department of Practice and Policy, School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK

    Frank M. C. Besag & Ian C. K. Wong

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  1. Shweta Anand
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Correspondence to Ian C. K. Wong.

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Conflict of interest

Shweta Anand, Henry Tong, Prof. Frank M.C. Besag, Dr. Esther W. Chan and Prof. Ian C.K. Wong declare no conflict of interest. Dr. Samuele Cortese has received grant or research support from the Solent National Health Service (NHS) Trust, UK. He has also received honorarium and travel expenses from the Association for Child and Adolescent Mental Health (ACAMH), UK, a non-profit organisation, all unrelated to this work.

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Anand, S., Tong, H., Besag, F.M.C. et al. Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment. Pediatr Drugs 19, 235–250 (2017). https://doi.org/10.1007/s40272-017-0224-6

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