Pharmacological treatment of sleep disturbance in developmental disabilities: A review of the literature

Sleep disturbance is a common problem in children with developmental disabilities. Effective pharmacologic interventions are needed to ameliorate sleep problems that persist when behavior therapy alone is insufficient. The aim of the present study was to provide an overview of the quantity and quality of pharmacologic research targeting sleep in children with developmental disabilities. Efficacy studies of medications most likely to be prescribed to children are reviewed in detail. Medline and PsychInfo searches were performed to identify relevant clinical trials and case reports, published between 1975 and 2009. Key search terms included sleep, children, antihistamines, alpha adrenergic agonists, antidepressants, antipsychotics, melatonin, ramelteon, benzodiazepines, and nonbenzodiazepines. The literature search identified 58 articles that met the inclusion criteria. Well-controlled studies employing both objective polysomnography and subjective sleep measures are needed to determine the efficacy and safety of currently prescribed pediatric sleep medicines. Melatonin appears to be the most widely assessed agent and safest choice for children with developmental disabilities. Trazodone, mirtazapine, and ramelteon hold promise but require further study.

Research highlights▶ Comprehensive literature search of pharmacological treatment of sleep disturbance in children and adults with developmental disabilities.▶ Key search terms included sleep, children, antihistamines, alpha adrenergic agonists, antidepressants, antipsychotics, melatonin, ramelteon, benzodiazepines, and nonbenzodiazepines (Z drugs).▶ Results Fifty eight articles met inclusion criteria. Twenty five controlled trials in typical children and children with developmental disabilities, 15 uncontrolled trials in children, and 18 controlled studies in adults.▶ Diphenhydramine use persists in pediatric populations with sleep problems, despite the lack of empirical evidence showing its effectiveness.▶ Clonidine's use as a hypnotic has not been adequately researched in pediatric populations, and it appears to decrease REM sleep.▶ Benzodiazepines carry a number of adverse effects, and the risks that undermine their use as hypnotics.▶ Zolpidem has not proven effective in the treatment of childhood insomnia. It may be useful in adolescents and adults.▶ Zaleplon has been studied in adults only, and it has been effective in reducing SOL but not fragmented sleep.▶ Imipramine is not recommended for use as a hypnotic as it may produce alerting effects.▶ Amitriptyline, improves sleep initiation and maintenance, but reduces REM sleep and may cause rebound insomnia following its discontinuation.▶ Melatonin appears to have the most empirical evidence for use and the best pharmacokinetic/dynamic profile treatment for sleep disorders.▶ Other promising hypnotics appear to be trazodone, mirtazapine, and ramelteon.