Insomnia: Recent Developments and Future Directions

Chapter 75 Insomnia


Recent Developments and Future Directions



Supported by MH024652, AG020677, and MH078961.


Research and clinical practice in insomnia have shown steady progress since the fourth edition of Principles and Practice of Sleep Medicine. These developments and the current state of knowledge are discussed in greater detail in the individual chapters in this section. This introductory chapter highlights and succinctly summarizes some of the most significant new findings and trends in four areas of insomnia: epidemiology; diagnosis and assessment; pathophysiology and biological findings; and treatment (Box 75-1).



Box 75-1 Recent Developments in Insomnia Research and Practice






One landmark event since the publication of the previous edition of this textbook was the 2005 State of the Science (SOS) Conference on Manifestations and Management of Chronic Insomnia in Adults, sponsored by the National Institutes of Health and supported by the American Academy of Sleep Medicine and the Sleep Research Society. The SOS conference summarized the state of clinical research and practice in insomnia and provided a guideline for future investigation.1 More specifically, the SOS conference recognized the substantial prevalence of insomnia, the need for further studies on longitudinal course, and the utility of the concept of “comorbid insomnia,” in contrast to the established notions of “secondary” versus “primary” insomnia (Video 75-1 image). The SOS conference reaffirmed the efficacy and limitations of currently available behavioral and pharmacologic treatments and emphasized the need for better evidence on the efficacy and safety of the many nonapproved drugs used to treat insomnia. Finally, the SOS conference called for the development of new pharmacologic agents with different mechanisms of action and for comparative efficacy trials involving both medications and behavioral treatments.



Epidemiology


Studies of insomnia epidemiology continue to document the high prevalence of the condition, as well as the variability in prevalence and incidence estimates based on the particular definition of insomnia used (see Chapter 76). A relative weakness in the epidemiology of insomnia concerns the sparse information regarding the longitudinal course of the disorder. However, studies from various countries using both cross-sectional and true longitudinal designs continue to demonstrate that insomnia is often a highly persistent condition, with approximately 40% of individuals reporting insomnia for 1 year or longer.24


It has long been recognized that insomnia is often comorbid with other psychiatric and medical conditions. More detail has begun to emerge regarding the strength of these associations.5 Most significantly, substantial evidence continues to accumulate documenting insomnia as a risk factor for subsequent mental disorders such as depression and their persistence.6,7 Insomnia has also been demonstrated to be a risk factor for adverse outcomes in depression, such as suicidal ideation in adolescents with depression.8 The links between insomnia and physical health remain less well defined, with evidence for and against risk for hypertension.9,10 Finally, evidence of the functional consequences of insomnia has become more refined and specific regarding quality of life, health care costs and utilization, sick leave, and disability.1114



Diagnosis and Assessment


The International Classification of Sleep Disorders, second edition (ICSD-2), was published in 2005.15 Although it retains basically the same categories of insomnia as its predecessor, the ICSD-2 for the first time also specifies criteria for general insomnia disorder, which are common to all of the specific insomnia subtypes (Video 75-2image). The criteria for general insomnia disorder emphasize not only the nighttime sleep complaint but also the presence of adequate opportunity for sleep and of specific types of daytime impairments. In this regard, the criteria follow closely with the research diagnostic criteria for insomnia published in 2004.16 The general insomnia disorder and research diagnostic criteria present specific diagnostic guidelines appropriate for both clinical and research use. However, operationalizing the impairment criteria and adequate opportunity for sleep will require further effort. The development of the Diagnostic and Statistical of Mental Disorders, fifth edition (DSM-V), the nosology used in the psychiatric community, is currently underway, with an anticipated publication date of 2012. The DSM-V sleep disorders work group is actively collaborating with the sleep medicine community and the American Academy of Sleep Medicine to ensure compatibility of different diagnostic systems.


Increasing attention has focused not only on the nighttime symptoms of insomnia but also on the daytime characteristics. The studies have included those focusing on the daytime symptoms of mood and attention difficulties17 but also on the documentation of impaired performance using neuropsychiatric assessments.1820 These studies show that insomnia sufferers have worse self-reported mood and performance, as well as greater variability of self-reported and objective impairments, compared with controls. Neuropsychological impairments appear to be most notable with complex tasks requiring shifting in task strategy, a function attributable to dorsolateral prefrontal cortex control. These deficits are associated with prefrontal hypoactivation on functional magnetic resonance imaging studies and suggest that impairments diminish with successful cognitive behavioral treatment.21 Strategies developed in the field of sleep and learning have also been applied to insomnia, with some preliminary evidence again documenting impairments in insomnia.22


A number of new rating scales for insomnia symptoms and impairments have been published or are under development. The Insomnia Severity Index23,24 has increasingly gained wide acceptance as an outcome measure in pharmacologic and behavioral treatment studies of insomnia. Qualitative research involving focus groups and patient interviews has also been used more widely for developing new patient report outcomes,25,26 in keeping with the U.S. Food and Drug Administration (FDA) Draft Guidance on Patient-Reported Outcome Measures.27 Additional rating scales developed with such techniques are under development by a number of academic and industry research groups.


Finally, an attempt to standardize research assessments for insomnia was published in 2006.28 One of the outcomes of this consensus process was the development of a standard sleep diary format, which was presented in preliminary form at the SLEEP 2008 meeting and is currently being finalized.



Pathophysiology and Biological Findings


Insomnia has long been considered to be a disorder of hyperarousal (see Chapter 78). Additional work has investigated the role of the hypothalamic-pituitary-adrenal axis in insomnia, both through physiological studies measuring the status and responsiveness of this system29 as well as the preliminary use of a corticotropin-releasing hormone antagonist to treat insomnia.30 The studies suggest that activation of the hypothalamic-pituitary-adrenal axis may contribute to the development of insomnia.


Quantitative electroencephalography has long been used as a potential marker of hyperarousal and or diminished homeostatic sleep drive. New evidence continues to suggest increased high frequency activity in at least some patients with insomnia, although the relationship of this finding to specific clinical features is less clear.31


Additional work in the neuroanatomy and functional neuroanatomy of insomnia has also been conducted, concurrent with important developments in basic sleep–wake neurobiology. For the first time, chronic insomnia has been associated with reduced hippocampal volume.32 Other techniques have also suggested abnormal brain function in insomnia. For instance, a magnetic resonance spectroscopy (MRS) study suggested decreased gamma-aminobutyric acid (GABA) in insomnia patients compared with controls, with a strong inverse correlation between data content and wakefulness after sleep onset.33 Positron emission tomography studies have shown a similar association between wake time after sleep onset (self-reported and polysomnographic) and glucose metabolism during non–rapid eye movement (NREM) sleep of brainstem, diencephalic, prefrontal, and limbic arousal systems.34


Plausible animal models of insomnia have also been developed and refined in the past several years that will provide insights into the pathophysiology of insomnia beyond those that can be achieved with human studies alone. Animal models include fear-conditioning studies in mice, which results in sleep disturbances similar to those observed in posttraumatic stress disorder with insomnia.35 A genetic screening technique has been used to identify and selectively breed Drosophila characterized by short sleep, prolonged sleep latency, sleep interruption, and waking consequences.36 This model provides the opportunity to examine not only genetic association with insomnia but also functional consequences of sleep disturbance and sleep loss in terms of gene regulation, gene products, and synaptic plasticity.37,38 A rodent model of behaviorally induced insomnia has also been described.39 The rat model of insomnia is associated with simultaneous activation of sleep-active and wake-active centers in the brain during NREM sleep. These findings may be a good model of the human condition of insomnia, in which individuals may perceive themselves as being awake during polysomnographically defined sleep.


Finally, additional work has continued regarding psychological models of insomnia in humans. In particular, new work has been focused on cognitive components of insomnia, including the development of safety responses and the involvement of selective attention as potential mechanisms for perpetuating insomnia.40,41

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Mar 13, 2017 | Posted by in NEUROLOGY | Comments Off on Insomnia: Recent Developments and Future Directions

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