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

ObjectiveA large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's well-being 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. MethodAfter 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, PsychInfo 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 randomized control trials (RCTs) and the Downs and Black checklist for non-RCTs. ResultsTwelve 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. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvement 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 except for zolpidem which was associated with neuropsychiatric adverse effects. ConclusionThere is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.

<p>Effects of melatonin in children with attention-deficit/hyperactivity disorder with sleep disorders after methylphenidate treatment</p>

“…Proof of the efficacy of melatonin in sleep latency and sleep duration in ADHD children has been supported by observational studies 16. Mohammadi et al17 explored the efficacy of melatonin in children with ADHD receiving MPH in a placebo-controlled study.…”

“…Proof of the efficacy of melatonin in sleep latency and sleep duration in ADHD children has been supported by observational studies. 16 Mohammadi et al 17 explored the efficacy of melatonin in children with ADHD receiving MPH in a placebo-controlled study. This study reported a positive effect of melatonin (3–6 mg/d) on sleep latency and overall sleep disturbances, without effects on ADHD measures.…”

A systematic meta-review of systematic reviews on attention deficit hyperactivity disorder

“…Seven systematic reviews reported about the efficacy of medication on ADHD symptoms in patients with comorbid disorders [149][150][151][152][153][154][155][156]. For example, both MPH and ATX were efficacious in reducing ADHD symptoms also in youth with ASD [149].…”

Pediatric Insomnia: Update and Future Directions

“…This is particu-larly an alarming given that the FDA (Food and Drug Administration) has not yet approved any medication for treatment of insomnia in children, even if many drugs are currently prescribed off-label for insomnia in children. [59][60][61] While prescription medication has not been approved, evidence form published studies in the past 15 years supports the overall efficacy and tolerability of melatonin for insomnia in children. [62][63][64][65][66] Melatonin is considered particularly beneficial for insomnia in children with autism 67,68 or special needs.…”