Kyle P. Johnson

Pharmacologic Management of Insomnia in Children and Adolescents: Consensus Statement

OBJECTIVE. The purpose of this work was to develop a consensus statement on the current status and future role for pharmacologic management of insomnia in children and adolescents. METHOD. The National Sleep Foundation, in collaboration with Best Practice Project Management, Inc, convened expert representatives involved in the study and treatment of pediatric insomnia and conducted a 2-day conference to examine the role of pharmacologic management of pediatric insomnia and to make recommendations regarding the development of clinical trials in this area. After a series of presentations providing background on the current knowledge of pediatric insomnia and its treatment alternatives, workgroups provided recommendations for the evaluation of pharmacologic treatment of insomnia in specific populations of children and adolescents and developed guidelines for the core methodologic issues relevant to the design of clinical trials. The group developed consensus recommendations for clinical trials in this area encompassing: (1) high-priority patient populations for research, (2) inclusion/exclusion criteria, (3) outcome measures, (4) ethical considerations unique to clinical trials involving children and adolescents, and (5) priorities for future research that will enhance the understanding of pediatric insomnia. RESULTS. Conference participants unanimously agreed that there is a need for pharmacologic management of pediatric insomnia. Furthermore, the widespread use of “hypnotic” and psychotropic medications for children in the absence of safety and efficacy data indicates a knowledge gap about the best pharmacologic practices for management of pediatric insomnia. Attendees reached consensus on methodologic issues in the study of pharmacologic treatment of pediatric insomnia including agreeing on a definition of pediatric insomnia as “repeated difficulty with sleep initiation, duration, consolidation, or quality that occurs despite age-appropriate time and opportunity for sleep and results in daytime functional impairment for the child and/or family.” It was agreed that priority should be given to insomnia studies in children with attention-deficit/hyperactivity disorder and those with pervasive developmental disorders/autism spectrum disorder. There was also agreement on the need for pharmacokinetic and pharmacodynamic studies to determine appropriate dose levels and to evaluate safety with a wide range of doses. CONCLUSIONS. The treatment of pediatric insomnia is an unmet medical need. Before appropriate pharmacologic management guidelines can be developed, rigorous, large-scale clinical trials of pediatric insomnia treatment are vitally needed to provide information to the clinician on the safety and efficacy of prescription and over-the-counter agents for the management of pediatric insomnia.

Sleep in children with autistic spectrum disorder.

Children and adolescents with autistic spectrum disorders (ASD) suffer from sleep problems, particularly insomnia, at a higher rate than typically developing children, ranging from 40% to 80%. Sleep problems in ASD might occur as a result of complex interactions between biological, psychological, social/environmental, and family factors, including child rearing practices that are not conducive to good sleep. Interestingly, children with a history of developmental regression have a more disturbed sleep pattern than children without regression. Even though regulation of sleep in children with ASD is still poorly understood, circadian abnormalities in autism might be the result of genetic abnormalities related to melatonin synthesis and melatonins role in modulating synaptic transmission. Recently a bifurcation of the sleep/wake cycle with increased sensitivity to external noise and short sleep duration causing irregular sleep onset and wake up times has been suggested. Identifying and treating sleep disorders may result not only in improved sleep, but also impact favorably on daytime behavior and family functioning. Several studies have also demonstrated effectiveness of behavioral interventions for sleep onset and maintenance problems in these populations. When behavioral interventions are not effective or lead only to a partial response, pharmacological treatment options should be considered. Studies of melatonin use in children with ASD provide evidence for its effectiveness and safety in the long run. The clinician assessing a child with an ASD should screen carefully for sleep disorders and make referrals as indicated.

Sleep Hygiene for Children With Neurodevelopmental Disabilities

Sleep disturbances in children with neurodevelopmental disabilities are common and have a profound effect on the quality of life of the child, as well as the entire family. Although interventions for sleep problems in these children often involve a combination of behavioral and pharmacologic strategies, the first line of treatment is the promotion of improved sleep habits or “hygiene.” Despite the importance of sleep-hygiene principles, defined as basic optimal environmental, scheduling, sleep-practice, and physiologic sleep-promoting factors, clinicians often lack appropriate knowledge and skills to implement them. In addition, sleep-hygiene practices may need to be modified and adapted for this population of children and are often more challenging to implement compared with their healthy counterparts. This first comprehensive, multidisciplinary review of sleep hygiene for children with disabilities presents the rationale for incorporating these measures in their treatment, outlines both general and specific sleep-promotion practices, and discusses problem-solving strategies for implementing them in a variety of clinical practice settings.

A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders

OBJECTIVE This report describes the development of a practice pathway for the identification, evaluation, and management of insomnia in children and adolescents who have autism spectrum disorders (ASDs). METHODS The Sleep Committee of the Autism Treatment Network (ATN) developed a practice pathway, based on expert consensus, to capture best practices for an overarching approach to insomnia by a general pediatrician, primary care provider, or autism medical specialist, including identification, evaluation, and management. A field test at 4 ATN sites was used to evaluate the pathway. In addition, a systematic literature review and grading of evidence provided data regarding treatments of insomnia in children who have neurodevelopmental disabilities. RESULTS The literature review revealed that current treatments for insomnia in children who have ASD show promise for behavioral/educational interventions and melatonin trials. However, there is a paucity of evidence, supporting the need for additional research. Consensus among the ATN sleep medicine committee experts included: (1) all children who have ASD should be screened for insomnia; (2) screening should be done for potential contributing factors, including other medical problems; (3) the need for therapeutic intervention should be determined; (4) therapeutic interventions should begin with parent education in the use of behavioral approaches as a first-line approach; (5) pharmacologic therapy may be indicated in certain situations; and (6) there should be follow-up after any intervention to evaluate effectiveness and tolerance of the therapy. Field testing of the practice pathway by autism medical specialists allowed for refinement of the practice pathway. CONCLUSIONS The insomnia practice pathway may help health care providers to identify and manage insomnia symptoms in children and adolescents who have ASD. It may also provide a framework to evaluate the impact of contributing factors on insomnia and to test the effectiveness of nonpharmacologic and pharmacologic treatment strategies for the nighttime symptoms and daytime functioning and quality of life in ASD.

Sleep Disturbances in Children With Psychiatric Disorders

Sleep disturbances are highly prevalent among children with psychiatric disorders, making recognition and management of pediatric sleep disorders an important step in improving treatment outcome and preventing relapse of mental illness. This chapter will review the research data on the epidemiology, clinical presentation and treatment approaches for sleep disorders frequently seen in the context of common psychiatric conditions in children and adolescents. Readers will learn about interaction between sleep related problems and symptoms of Attention Deficit/Hyperactivity Disorder, Anxiety and Mood Disorders and Autism Spectrum Disorders, and about the impact of sleep loss and sleep fragmentation on the emotional and behavioral development in children.

The relationship between sleep problems and daytime behavior in children of different ages with autism spectrum disorders.

BACKGROUND The purpose of the current study was to evaluate the relationships among sleep problems and daytime behaviors in a large, well-defined cohort of children with autism spectrum disorder (ASD). METHODS Out of a registry population of 3452 children with ASDs, a subset of 1193 children aged 4 to 10 years of age from 14 centers across the country was used to evaluate the relationship between varying levels of sleep problems and daytime behavior. Measures included Children’s Sleep Habits Questionnaire, Vineland Adaptive Behavior Scales, Survey Interview Form, Second Edition, and Child Behavior Checklist. Multiple analysis of covariance was used to assess the association between sleep and behavior. RESULTS Results suggest that sleep problems, as identified by parent report by use of the Children’s Sleep Habits Questionnaire, have a negative relationship with daytime behavior. More specifically, children with ASDs and sleep problems had more internalizing and externalizing behavior problems, as measured by the Child Behavior Checklist, and poorer adaptive skill development, as measured by the Vineland Adaptive Behavior Scales, than children with ASDs and no sleep problems. Children with moderate to severe sleep problems had greater behavior difficulties, but not necessarily poorer adaptive functioning, than children with mild to moderate sleep problems. Both preschool- and school-aged children demonstrated a negative relationship between behavior and sleep, whereas the relationship between sleep and adaptive functioning was much more variable. CONCLUSIONS These results suggest that, although sleep has a negative relationship with internalizing and externalizing behavior, it may have a different relationship with the acquisition of adaptive skills.

Sleep Patterns in Autism Spectrum Disorders

Like children with other developmental disabilities, children with autism spectrum disorders suffer from sleep problems at a greater rate than typically developing children. It is increasingly recognized that addressing these sleep problems may improve daytime functioning and decrease family stress. The sleep problems experienced by children with autism spectrum disorders are presented in this article.

Review of Disrupted Sleep Patterns in Smith-Magenis Syndrome and Normal Melatonin Secretion in a Patient with an Atypical Interstitial 17p11.2 Deletion

Smith–Magenis syndrome (SMS) is a disorder characterized by multiple congenital anomalies and behavior problems, including abnormal sleep patterns. It is most commonly due to a 3.5 Mb interstitial deletion of chromosome 17 band p11.2. Secretion of melatonin, a hormone produced by the pineal gland, is the bodys signal for nighttime darkness. Published reports of 24‐hr melatonin secretion patterns in two independent SMS cohorts (US and France) document an inverted endogenous melatonin pattern in virtually all cases (96%), suggesting that this finding is pathognomic for the syndrome. We report on a woman with SMS due to an atypical large proximal deletion (∼6Mb; cen<‐>TNFRSFproteinB) of chromosome band (17)(p11.2p11.2) who presents with typical sleep disturbances but a normal pattern of melatonin secretion. We further describe a melatonin light suppression test in this patient. This is the second reported patient with a normal endogenous melatonin rhythm in SMS associated with an atypical large deletion. These two patients are significant because they suggest that the sleep disturbances in SMS cannot be solely attributed to the abnormal diurnal melatonin secretion versus the normal nocturnal pattern.

Mental Health Utilization in a Pediatric Emergency Department

Objective Mental health complaints are frequent in the pediatric emergency department (PED). The objective of this study was to describe trends over time in PED utilization for mental health care at in a single pediatric tertiary care hospital. It is our hypothesis that the resources used by this patient population are high and that mental health-related visits have increased over the most recent decade. Methods This was a retrospective study of all pediatric mental health presentations to the PED from January 2009 to July 2013 at a single pediatric hospital. All patients aged 1 to 19 years with an International Classification of Diseases, Ninth Revision code of 291, 292, 295 to 309, and 311 to 314 were included. Data collected included demographic data, medications received, restraint use, suicidality, length of stay (LOS), charges incurred, final disposition, and daily PED operation variables. Trends over time in presentation, charges, and LOS were analyzed using multiple mixed effects regression models after adjusting for potential patient and PED level confounding variables and clustering of multiple visits within patients. Results A total of 732 PED visits from 2009 to 2013 were identified representing 646 unique patients. The average age was 13.8 years, and 53% were male. Approximately 25% of the patients expressed suicidal ideation, and 44% of those had attempted suicide before arrival. Behavioral or chemical restraints were used in 33% of patients during their PED visit. There were statistically significant increases in annual visits, LOS, and charges over this period (P < 0.05). Increased charges were significantly associated with longer LOS (P = 0.0062). Charges (P = 0.46) and LOS (P = 0.62) were not significantly different between suicidal and nonsuicidal patients. Approximately 21% of patients were admitted or transferred to another facility. Conclusions In this single-center study, we found evidence that the resources required to care for pediatric patients with mental health complaints have increased significantly over time both by increased number of annual visits and an increasing LOS. Further research is necessary to determine if our data are consistent with national trends to further our understanding of the problem and improve resource allocation.

Nocturnal Sleep–Wake Parameters of Adolescents at Home Following Cancer Chemotherapy

Purpose: The purpose of this descriptive, longitudinal study was to describe objective nocturnal sleep–wake parameters of adolescents at home after receiving chemotherapy in the hospital or outpatient clinic and explore differences in sleep variables by age, gender, and corticosteroid use. Methods: We collected 7 days of wrist actigraphy and sleep diary data from 48 adolescents (10–19 years) who were receiving cancer chemotherapy for a primary or secondary cancer or a relapse. The actigraphic sleep variables included rest interval (i.e., time in bed), sleep onset, sleep offset, sleep duration, total sleep time (TST), wake after sleep onset (WASO), and %WASO. Results: Of the 48 adolescents, 38 had at least five nights of scored actigraphy and were included in analyses. Older (13–18 years) adolescents went to bed later and had fewer minutes of TST than younger adolescents (10–12 years). Exploratory analyses revealed no differences between adolescents who were taking oral corticosteroids (i.e., prednisone, dexamethasone) and those who were not or between males and females. Conclusion: These adolescents had sleep durations that met or exceeded the recommended sleep duration for their age groups but experienced significant WASO. Further research is needed to estimate sleep needs of adolescents during chemotherapy and determine factors that contribute to nocturnal wake-time so that targeted interventions can be designed to improve sleep quality.