National Sleep Disorders Research Plan
 
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Section 5 Content:
Narcolepsy and Other Hypersomnias  
Restless Legs Syndrome/Periodic Limb Movement Disorders
Sleep in Other Neurological Disorders  
Parasomnias
Sleep in Psychiatric, Alcohol and Substance Use Disorders
Immunomodulation, Neuroendocrinology and Sleep   
Sleep-Disordered Breathing
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 








SECTION 5 - SLEEP DISORDERS

Insomnia


Adult

Background

Insomnia is defined as difficulty falling asleep, difficulty staying asleep, or short sleep duration, despite having an adequate opportunity for sleep. It is the most common sleep complaint, affecting approximately 30-40% of the adult population. Even when more stringent criteria are required, such as daytime impairment or marked distress, insomnia disorders have a prevalence of approximately 10%. Evidence suggests that insomnia has significant consequences on quality of life, healthcare utilization, and subsequent psychiatric disorders. Efficacious short-term behavioral and pharmacologic treatments for insomnia are available, and progress has been made in epidemiology and risk factor identification, in identification of adverse outcomes, and in identifying effective treatments.

However, there is still much we do not know regarding the causes, characterization, consequences, and optimal management of insomnia disorders. For instance, we do not have a consistent phenotype(s) for insomnia disorders that could be applied to human and animal studies. Despite major advances in the neurobiology of sleep and circadian rhythms (Section I), the implications of these findings for insomnia have not been carefully investigated. Instead, the pathophysiology of insomnia has been examined from a number of clinically derived theoretical frameworks, with little replication of the findings reported in individual studies. Effective treatments for Insomnia have been developed, but important issues still remain. For instance, the exportability of behavioral treatments to usual care settings and the effectiveness (as opposed to efficacy) of insomnia treatments have yet to be determined. Finally, there is a need to develop novel pharmacologic treatments based on new findings in sleep neurobiology.

Progress In The Last Five Years

- The efficacy and durability of standardized behavioral treatments for insomnia have been demonstrated in a number of well-controlled clinical trials.

- The epidemiology of insomnia in adults has been well described. Consistent risk factors, such as psychological symptoms, medical illness, and female sex, have been identified.

- Independent studies have demonstrated that insomnia is a risk factor for subsequent development of psychiatric disorders, and for worse outcomes among individuals with concurrent psychiatric disorders.

- A small but growing body of evidence has demonstrated "hyperarousal" among patients with insomnia, including increased central nervous system activation (indexed by increased high-frequency EEG activity), sympathetic nervous system activation, and hypothalamic-pituitary-adrenal axis activation.

Research Recommendations

- Basic and pre-clinical studies are needed that focus on the neurobiology of insomnia. These should include (1) the development of animal models of insomnia with specific insomnia phenotypes, (2) the application of neurophysiological, neurochemical, neuroanatomic, and functional neuroimaging approaches to human studies, and (3) genetic, genomic, and proteomic studies.

- Pharmacological treatment studies are needed to define the efficacy, safety, abuse liability and role of long-term hypnotic treatment. Priority should be given to studies defining the optimal duration and pattern of administration of traditional hypnotic medications, including investigations of their use in populations with high rates of utilization such as with psychiatric disorders. Studies are also needed on widely used but poorly-documented treatments, such as sedating antidepressants, and on the development and testing of novel pharmacologic agents based on neuroscience findings (e.g., drugs affecting corticotropin release, adenosine, or hypocretin systems).

- Insomnia phenotypes need to be characterized. This includes (1) development and validation of clinical phenotypes (e.g., define diagnostic criteria), (2) physiological characterization and biomarkers (which may include measures of EEG, HPA axis, sympathetic nervous system, and functional neuroanatomy using neuroimaging techniques), and (3) indices of discriminant validity versus mood and anxiety disorders. Definition of insomnia phenotypes should also address subjective-objective discrepancies in sleep measures, as well as the relationship between insomnia and co-existing sleep, psychiatric, and physical disorders.

- Further studies of behavioral/ psychological treatments are needed. These studies should include (1) the use of behavioral/ psychological treatments in routine care settings (e.g., primary care offices), (2) the development of alternative delivery methods (e.g., simplified treatment regimens, computer or Internet administration), (3) studies in patients with medical or psychiatric comorbidity, and (4) large-scale effectiveness studies. Priority should also be placed on investigating the specific efficacious components of these behavioral treatments.

- More precisely define the potential physical health risks, morbidity, and functional consequences of insomnia, distinct from the morbidity and consequences of associated medical and psychiatric conditions.

- Examine the extent of use, efficacy, and adverse effects associated with alternative treatment approaches, including nutritional supplements, herbal remedies, and non-pharmacological treatments.

Pediatric

Background

Difficulties in initiating and maintaining sleep are extremely common in children. The overall prevalence of sleep onset delay/bedtime resistance has been reported to be in the range of 15 - 25% in healthy school-aged children and even higher in adolescents. However, because behaviorally-based sleep problems in children are often defined by caregivers, the range of sleep behaviors that may be considered "normal" or "pathologic" is wide and the definitions highly variable. In addition, population-based normative data on sleep patterns across childhood are lacking, creating further challenges in defining "abnormal" sleep in infants, children, and adolescents. Thus, a common nosology for defining sleep disorders in children needs to be developed and evaluated.

Insomnia in Special Populations:

Sleep disturbances in pediatric special needs populations are extremely common, and often a source of considerable stress for families. Prevalence of sleep problems in children with severe mental retardation has been estimated to be as high as 80%, and to be 50% in children with less severe cognitive impairment. The prevalence of sleep problems in autism is estimated to be 50 to 70%.

Significant problems with initiation and maintenance of sleep, shortened sleep duration, irregular sleeping patterns, and early morning waking have been reported in many neurodevelopmental disorders, including autism and pervasive developmental disorder, Asperger's syndrome, Smith-Magenis syndrome, Angelman's syndrome, tuberous sclerosis, San Filippo syndrome, Rett syndrome, and William syndrome. Other studies have suggested that similar rates of sleep problems also occur in both younger and older blind children, the most common concerns being difficulty falling asleep, night wakings, and restless sleep.

The types of sleep disorders in these children are not unique to this population, but are more frequent and more severe than in the general population, and often reflect the child's developmental level rather than chronological age. Multiple sleep disorders are also likely to occur simultaneously. The incremental impact of disrupted and/or inadequate sleep on cognitive, emotional, and social development and behavior in these already at-risk children is potentially profound.

Little is understood about the interaction between sleep disorders and acute and chronic health conditions such as asthma, diabetes, and juvenile rheumatoid arthritis on either a pathophysiologic or behavioral level. In chronic pain conditions, these interactions are likely to significantly impact morbidity and quality of life.

Progress In The Last 5 Years

- In addition to risk factors such as social and communication developmental abnormalities and cognitive impairment, a primary arousal dysfunction in children with neurodevelopmental disorders may contribute to sleep problems.

- There may also be a primary disturbance of melatonin production and synchronization in autistic children, and some autistic children seem to respond to treatment with exogenous melatonin. Studies have documented improvements in sleep onset delay, night wakings, early morning waking and total hours of sleep using a small dose (0.3-0.5 to 2.5-5 mg) of melatonin approximately one hour before desired bedtime in up to 80% of children with disorders such as cortical blindness, Rett syndrome, autism, tuberous sclerosis, and Asperger's syndrome. However, melatonin is not effective in all developmentally delayed children with sleep problems and little is known overall about long-term side effects.

- A few studies have examined the role of sleep disturbances in chronic medical conditions of childhood such as sickle cell disease and asthma, disorders particularly common in high risk and minority populations. The interaction between sleep and physical and emotional dysfunction in acute and chronic pain conditions such as burns and juvenile rheumatoid arthritis has also begun to be explored. Additional factors such as the impact of hospitalization, family dynamics, underlying disease processes, and concurrent medications are also important in assessing the bi-directional relationship of insomnia and chronic illness in children.

- Clinical psychology and pediatric studies have examined the efficacy of empirical behavioral treatment for sleep problems in small samples. Most of these studies have relied on parental assessment of treatment success. Additional outcomes research to systematically assess efficacy of various treatment modalities for sleep disorders, including behavioral management protocols, is needed to generate recommendations for "best practices."

- Pharmacologic intervention in conjunction with behavioral techniques has been shown to be effective in some cases. However, little is known overall about the safety and efficacy of pharmacologic interventions for sleep disturbances in children, alone or in combination with behavioral therapy. Medications used to treat insomnia in children include diphenhydramine, chloral hydrate, trazadone, clonidine, and benzodiazepines. Hypnotic medications, however, can result in unpredictable side effects, development of tolerance necessitating increasingly higher doses, paradoxical effects (agitation instead of sedation), and withdrawal effects. Rebound sleep onset delay on discontinuation and morning "hangover" can be significant problems as well. Little is known about the scope and patterns of use of pharmacologic interventions in pediatric sleep disorders, about possible indications, and about potential target populations for short-term use of hypnotics in conjunction with behavioral interventions.

Research Recommendations

- Develop a common definition and document the prevalence and functional impact of pediatric insomnia across the age spectrum in the general population, and in high-risk populations such as special needs children (e.g., neurodevelopmental disorders, sensory deficits) and children with chronic medical conditions (e.g., diabetes, asthma). Normative data will need to be collected regarding sleep practices and patterns in order to define "abnormal" sleep. Studies will need to examine the developmental aspects of insomnia in children, including the role of early sleep patterns and behaviors, parenting practices, temperament, and genetics, and risks and protective factors for the persistence of insomnia into adolescence and adulthood.

- Develop and evaluate optimal evidence-based treatment strategies and management protocols for pediatric insomnia:

> In otherwise healthy children, using standardized measures for such outcome variables as sleep quality and quantity, sleepiness/alertness, mood, behavior, academic functioning and parental stress.

> In children with special needs, including evidence-based behavioral and pharmacologic treatments for insomnia and circadian rhythm disturbances, and including outcome measures such as neurocognitive performance measures and assessment of impact on quality of life for children and caregivers.

- Examine the interrelationships between insomnia and chronic medical conditions in children, including effects on disease processes, pain management, quality of life and caregiver well being.

 
National Institutes of Health (NIH) Department of Health and Human Services (click here) First Gov Website (Click here)
National Heart Lung and Blood Institute (Click Here) National Center on Sleep Disorders Research (Click Here)