Pharmacotherapeutic management of sleep disorders in children with neurodevelopmental disorders

ABSTRACT

Introduction: Sleep disturbances are highly prevalent in children with neurodevelopmental disabilities. Without appropriate treatment, sleep disorders can become chronic and last for many years. However, there are no sleep medications approved by the United States Food and Drug Administration and only one has been approved by the European Medicines Agency for pediatric insomnia; thus, most medications are prescribed off-label.

Areas covered: In this narrative review, the authors highlight and summarize the most common drugs and supplements used for the treatment of sleep problems in children with neurodevelopmental disabilities. Recommendations are formulated regarding the use of melatonin and melatonin receptor agonists, sedating antidepressants, antipsychotics, antihistamines, gabapentin, clonidine and orexin receptor antagonists, and benzodiazepines and hypnotic benzodiazepine receptor agonists.

Expert opinion: The choice of pharmacological agents and their dosage should be individualized taking into consideration multiple factors, including the severity and type of sleep problem and the associated neurological pathology. Melatonin is widely used and safe in children with neurodevelopmental conditions. Gabapentin, clonidine, trazodone, and mirtazapine hold promise but require further study. Supplements (iron, vitamin D, and 5-hydroxytryptophan) might be helpful. Due to the lack of clinical data, there is still uncertainty concerning dosing regimens and tolerability.

KEYWORDS:

• Sleep disorders
• insomnia
• neurodevelopmental disorders
• drug effects
• melatonin

Declaration of interest

O Bruni has served as a consultant and provided expert testimony for both Angelini and Farmaceutici S.p.A. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares that they participated in the development of prolonged-release melatonin minitablets for children with ASD which got approved last year by the EMA. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Article highlights

• Sleep disturbances are associated with NDDs in as many as 70% of cases.

• Both subjective (i.e., detected with questionnaires) and objective (i.e., revealed by actigraphy or neurophysiologic tools) sleep alterations have been found to be significantly more frequent in individuals with NDDs, compared to controls.

• Clinicians should screen for sleep disturbances in patients with NDDs at each visit.

• There is a paucity of empirical evidence to guide treatment of sleep disturbances in NDDs.

• Melatonin and other pharmacological treatments, such as gabapentin, clonidine, trazodone, and mirtazapine, can constitute a valid option in the case of inefficacy of behavioral treatment.

• More rigorous evaluations of therapeutic strategies for sleep disorders are needed in individuals with NDDs. RCTs of pharmacological and non-pharmacological interventions will be valuable to support the clinician in making evidence-based decisions in daily clinical practice.

This box summarizes key points contained in the article.

Additional information

Funding

This manuscript has not been funded.