Anna Ivanenko

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 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.

Development of the Pediatric Restless Legs Syndrome Severity Scale (P-RLS-SS)©: A patient-reported outcome measure of pediatric RLS symptoms and impact

OBJECTIVE To develop a questionnaire to measure Pediatric Restless Legs Syndrome (P-RLS) symptoms and impact for use in clinical research. METHODS Questionnaire items were developed based on open-ended, qualitative interviews of 33 children and adolescents diagnosed with definite RLS (ages 6-17 years) and their parents. The draft questionnaire was then tested through cognitive debriefing interviews with 21 of the same children/adolescents and 15 of their parents. This involved the children and parents answering the draft items and then interviewing them about the childs ability to understand and interpret the questionnaire. Expert clinicians provided clinical guidance throughout. RESULTS Draft severity questions were generated to measure the four-symptom and four-impact domains identified from the concept elicitation interviews: RLS sensations, move/rub due to RLS, relief from move/rub, pain, and impact of RLS on sleep, awake activities, emotions, and tiredness. RLS descriptions, symptoms, and impact were compared between those who had comorbid attention-deficit/hyperactivity disorder and those who did not. Revisions to several questions were made based on the cognitive debriefing interviews and expert clinician review, resulting in a severity scale with 17 morning and 24 evening items. Caution regarding self-administration in children ages 6-8 years is recommended. To complement the child/adolescent measures, a separate parent questionnaire was also developed. CONCLUSIONS The P-RLS-SS was constructed based on detailed input from children and adolescents with RLS, their parents, and clinical experts, thus providing a scale with strong content validity that is intended to be comprehensive, clinically relevant, and important to patients. Validation of this scale is recommended.

Pediatric Restless Legs Syndrome: Analysis of Symptom Descriptions and Drawings

The specific aims of this study were to collect and analyze detailed symptom descriptions from patients with pediatric restless legs syndrome, ages 6 to 17 years, as well as assess symptom impact and the usefulness of drawings. Trained qualitative interviewers conducted face-to-face audio-recorded interviews of children and adolescents who met criteria for definite restless legs syndrome. Thirty-three patients in 3 age groups used 16 different categories of descriptors for restless legs sensations, with a mean of 3 or more categories used per patient in each age group. “Need to move/kick,” “pain/hurts,” “uncomfortable/cannot get comfortable,” and “like bugs or ants/crawling” were the most common descriptors. Two-thirds reported daytime sensations, and nearly half had arm involvement. They described impact on sleep, cognitive function, and affect. Drawings provided useful diagnostic information. These detailed empirical data will be useful in clinical practice, as well as in the development of formal diagnostic tools and severity measures.

A One-Hour Sleep Restriction Impacts Brain Processing in Young Children Across Tasks: Evidence From Event- Related Potentials

The effect of mild sleep restriction on cognitive functioning in young children is unclear, yet sleep loss may impact childrens abilities to attend to tasks with high processing demands. In a preliminary investigation, six children (6.6–8.3 years of age) with normal sleep patterns performed three tasks: attention (“Oddball”), speech perception (consonant–vowel syllables), and executive function (Directional Stroop). Event-related potentials (ERPs) responses were recorded before (Control) and following 1 week of 1-hour per day of sleep restriction. Brain activity across all tasks following Sleep Restriction differed from activity during Control Sleep, indicating that minor sleep restriction impacts childrens neurocognitive functioning.

Classification and Epidemiology of Sleep Disorders

Sleep disturbances are common in children and adolescents but still remain underrecognized and undertreated. Several classification systems of sleep disorders are available, including some newer attempts to develop more specific nosologic categories that reflect developmental aspects of sleep. The prevalence of sleep disorders has been studied across various samples of healthy, normal children and in children with special medical and neurodevelopmental needs. Sleep disorders are more frequently seen in children and adolescents with psychiatric disorders, making it very important for mental health professionals to be aware of sleep problems and to address them in the context of psychiatric comorbidities.

Sleep in Children With Psychiatric Disorders

Sleep disturbances are common in pediatric psychiatric disorders and constitute key elements in diagnostic symptomatology of various primary psychiatric disorders including bipolar disorder, depression, and anxiety disorder. Although sleep is not included in key defining criteria of some impairing illnesses such as obsessive-compulsive disorder and schizophrenia, these disorders present with a very high prevalence of sleep disturbances. The interaction between sleep and psychopathology is very complex with significant interrelationship in development, severity, and prognosis of psychiatric disorders and comorbid sleep disturbances. The research ranging from small intervention case series to large epidemiologic studies have demonstrated the role of specific sleep complaints in specific psychiatric diagnoses. However, the research using objective instruments such as polysomnography and actigraphy remains limited in youth with psychiatric disorders. The intervention studies using pharmaceutical treatment specifically focusing on sleep disturbances in psychiatric disorders are also sparse in the pediatric literature. Early identification of sleep disturbances and behavioral management using cognitive behavior therapy-based tools appear to be the most effective approach for treatment. The use of psychotropic medications such as selective serotonin reuptake inhibitors for the treatment of primary psychiatric disorder often alleviate the psychological barriers for sleep but may lead to emergence of other sleep issues such as restless leg syndrome. The safety and efficacy data of hypnotics for primary sleep disorders are limited in pediatrics and should be avoided or used with extreme caution in children with comorbid sleep and psychiatric problems.

Sleep-Related Hallucinations

Sleep-related hallucinations are a type of perceptual experience that occurs during transition to sleep or at awakening and can be of any sensory modality. Hypnagogic hallucinations occur at sleep onset while hypnopompic hallucinations occur at awakening. Nocturnal hallucinations have been reported in normal individuals, however, they occur more frequently in patients with various clinical conditions, especially in narcolepsy. Evaluation of sleep-related hallucinations involves comprehensive clinical assessment with laboratory investigations when other neurological or sleep disorders are suspected. There is no specific treatment for sleep-related hallucinations. In most uncomplicated cases they resolve with reassurance. Management of underlying causes of hallucinations is usually effective in reducing their frequency and intensity.

Sleep in Adolescents with Psychiatric Disorders

Sleep disturbances are an essential part of the current DSM-V diagnostic criteria for depressive disorder and posttraumatic stress disorder (PTSD). Numerous studies have reported subjective sleep symptoms in adolescents with depressive disorders and anxiety. There have been several studies to identify the objective markers of depression using sleep measures such as polysomnography and actigraphy in adolescents. However, the results have been variable in the parameters used and inconsistent in the findings.