Michael J. Sateia

International Classification of Sleep Disorders-Third Edition: Highlights and Modifications

The recently released third edition of the International Classification of Sleep Disorders (ICSD) is a fully revised version of the American Academy of Sleep Medicines manual of sleep disorders nosology, published in cooperation with international sleep societies. It is the key reference work for the diagnosis of sleep disorders. The ICSD-3 is built on the same basic outline as the ICSD-2, identifying seven major categories that include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders. Significant modifications have been made to the nosology of insomnia, narcolepsy, and parasomnias. Major features and changes of the manual are reviewed in this article. The rationales for these changes are also discussed.

Contemporary Reviews in Sleep MedicineInternational Classification of Sleep Disorders-Third Edition

The recently released third edition of the International Classification of Sleep Disorders (ICSD) is a fully revised version of the American Academy of Sleep Medicines manual of sleep disorders nosology, published in cooperation with international sleep societies. It is the key reference work for the diagnosis of sleep disorders. The ICSD-3 is built on the same basic outline as the ICSD-2, identifying seven major categories that include insomnia disorders, sleep-related breathing disorders, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, sleep-related movement disorders, parasomnias, and other sleep disorders. Significant modifications have been made to the nosology of insomnia, narcolepsy, and parasomnias. Major features and changes of the manual are reviewed in this article. The rationales for these changes are also discussed.

Neuropsychological impairment and quality of life in obstructive sleep apnea

Although clinical experience has suggested for more than two decades that OSA is associated with impairment of cognition, emotional state, and quality of life and that treatment with nasal CPAP produces significant improvements in these areas, sound empirical evidence to support this view, especially regarding treatment outcome, has been lacking. More recent investigations have begun to provide this support from randomized, adequately controlled studies. These assessments suggest that some degree of cognitive dysfunction is associated with OSA. The effects are most apparent in the severe cases, whereas results in mild cases are more equivocal. Reported impairments include global intellectual dysfunction and deficits in vigilance, alertness, concentration, short- and long-term memory, and executive and motor function. Considerable discrepancy exists across studies with respect to type and degree of dysfunction, however. Disturbances in general intellectual function and executive function show strongest correlations with measures of hypoxemia. Not unexpectedly, alterations in vigilance, alertness, and, to some extent, memory seem to correlate more with measures of sleep disruption. Although many inadequately controlled investigations have demonstrated reversibility of most or all of these deficits with effective treatment, more recent placebo-controlled studies have raised doubts regarding whether the observed changes are truly a function of treatment. This issue requires further systematic exploration with adequate controls and step-wise analysis of treatment duration effects. A similar set of considerations exists with respect to the relationship between psychological disturbance, primarily depression, and OSA. Although several studies suggest significant depression in these patients, the results are mixed. Placebo-controlled treatment trials fail to demonstrate consistently a difference in mood improvement between active treatment groups and controls, although several methodologic considerations suggest that these results should be interpreted with caution. Numerous investigations leave little doubt about the issue of quality of life impairment among persons with OSA. Further characterization of impairment, particularly in areas specific to this population, will provide clearer understanding of the problem. Preliminary investigations of treatment response in controlled studies indicate significantly greater improvement of quality of life in response to CPAP. Although patients with OSA commonly report disturbances in cognitive and psychological function and general quality of life, the increased rates of obesity, hypertension, diabetes, cardiovascular disease, medication use, and related psychosocial complications present a host of potential etiologies that might explain the impairments noted. There can be little doubt that these covariants do, in some cases, contribute to neuropsychological dysfunctions. It is essential that future studies continue to define those disturbances that are specific to OSA, the relationship between levels of severity and impairment, the role of treatment in reversing these dysfunctions, and the correlation between test results and significant day-to-day social and occupational functional impairment.

Acute effects of mirtazapine on sleep continuity and sleep architecture in depressed patients: a pilot study.

BACKGROUND Mirtazapine, a clinically effective antidepressant, acts by antagonizing central alpha2-adrenergic and 5-HT2/5-HT3 receptors. No data are available regarding mirtazapines effects on sleep architecture in patients with major depressive disorder. METHODS Six patients meeting criteria for major depressive disorder and scoring > or =4 on the three Hamilton Depression Rating Scale sleep items were studied. Polysomnographic evaluations were performed at baseline and after 1 (15 mg at bedtime) and 2 weeks (30 mg at bedtime) of open-label mirtazapine treatment. RESULTS Mirtazapine significantly decreased sleep latency and significantly increased total sleep time and sleep efficiency from baseline levels during week 1, with similar results observed after week 2. Mirtazapine did not significantly alter rapid eye movement sleep parameters. Clinically, Hamilton Depression Rating Scale and sleep disturbance ratings improved after treatment. CONCLUSIONS Mirtazapine significantly improves sleep continuity in major depressive disorder patients with poor sleep quality at weeks 1 and 2 of treatment, while preserving sleep architecture.

Distinguishing between excessive daytime sleepiness and fatigue: toward improved detection and treatment.

INTRODUCTION Excessive daytime sleepiness (EDS) and fatigue occur in high percentages in the general population. They are common complaints in primary care and in specialty medicine. Although they may represent distinct or overlapping phenomena, the general medical literature does not normally distinguish between EDS and fatigue. Despite their prevalence, both EDS and fatigue are identified and treated in a relatively small proportion of those affected. The similarity of EDS and fatigue may create diagnostic ambiguity and thereby contribute to under-identification and under-treatment. Fatigue, in particular, is thought to be difficult to manage when it is identified. METHODS The literature was searched for reviews, meta-analysis and similar levels of papers focused on EDS or fatigue. RESULTS EDS and fatigue are operationalized in ways that contribute to blurring rather than to distinguishing between them. Existing measures of both EDS and fatigue may also contribute to their misidentification. Effective treatments for both symptoms have been established. Behavioral interventions are effective and underutilized. DISCUSSION We suggest more precise operationalization of EDS and fatigue, leading to a refinement of existing measures or development of new tools, a structured interview with fatigue and EDS sections in the clinical setting, and more consideration for behavioral interventions.

Update on Sleep and Psychiatric Disorders

Current data demonstrate a high rate of comorbidity between sleep disorders and various psychiatric illnesses, especially mood and anxiety disorders. The disturbance of sleep quality and continuity that is associated with many sleep disorders predisposes to the development or exacerbation of psychological distress and mental illness. Likewise, the presence of psychiatric illness may complicate the diagnosis and treatment of sleep disorders. This focused review examines the literature concerning the interaction between major International Classification of Sleep Disorders, 2nd edition, diagnoses and psychiatric conditions with respect to sleep findings in various psychiatric conditions, psychiatric comorbidity in sleep disorders, and reciprocal interactions, including treatment effects. The data not only underscore the high frequency of psychopathology and psychological distress in sleep disorders, and vice versa, but also suggest that combined treatment of both the mental disorder and the sleep disorder should become the standard for effective therapy for all patients.

Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline

INTRODUCTION The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults. METHODS The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations. RECOMMENDATIONS The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of evidence in published data. Downgrading the quality of evidence for these treatments is predictable in GRADE, due to the funding source for most pharmacological clinical trials and the attendant risk of publication bias; the relatively small number of eligible trials for each individual agent; and the observed heterogeneity in the data. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. We suggest that clinicians use suvorexant as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use eszopiclone as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zaleplon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zolpidem as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use triazolam as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use temazepam as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use ramelteon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use doxepin as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tiagabine as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use diphenhydramine as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use melatonin as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tryptophan as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use valerian as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK).

Efficacy and clinical safety of ramelteon: An evidence-based review

Ramelteon is a novel hypnotic compound that is FDA-approved for the treatment of sleep-onset difficulty. It is a melatonin 1/2 receptor agonist with rapid absorption, extensive first-pass metabolism and an elimination half-life of just over 1h. Clinical efficacy data indicate moderate efficacy in reduction of sleep latency in adults of all ages with chronic insomnia, with estimated effect sizes roughly comparable to other standard hypnotic agents. Objective studies show minimal increases in total sleep time and no significant impact on wake after sleep-onset or sleep-stage distribution. Subjective reports demonstrate comparable, if slightly smaller, improvements. The recommended dosage is 8mg but studies suggest a flat response across dosage ranges from 4 to 32mg. Safety data indicate no evidence of clinically significant next-day performance effects and a reasonably low side effect profile. Animal studies, and a single human study suggest low abuse potential. Single-blind run-out from clinical trials have demonstrated no evidence of rebound insomnia.

The need for a knowledge system in sleep and chronobiology.

Sleep problems and the disorders that cause them influence health-related quality of life as much as other chronic medical conditions. Of the total U.S. population, 20–35% regularly suffer from insomnia. Only 40% of the time is insomnia associated with psychological distress or psychiatric disease; more commonly it is associated with medical illness or with behavioral traits or habits. Sleepiness severe enough to hamper the activities of daily living is estimated to be present in 30% of the population and is most commonly caused by voluntary restriction of sleep time. Sleep apnea and restless-legs syndrome, common medical causes of sleepiness, are present in some 2–4% of the population and in higher prevalence (10–40%) in those with neuromuscular diseases, renal failure, hypertension, and heart disease. Diagnostic strategies and/or effective interventions are available for insomnia and sleepiness, and for sleep and circadian rhythm disorders. Moreover, epidemiologic studies show that for a condition such as sleep apnea, 80% of men and 90% of women with clinically significant illness remain undetected and/or undiagnosed. The underdiagnosis and undertreatment of sleep disorders is understandable, if not excusable, considering the lack of representation of the topics of sleep and chronobiology in current medical school curricula. A 1990 survey of 126 United States medical schools could document only an average of 1.16 hours per school of instruction in sleep and sleep disorders throughout a four-year program; however, the variance was wide, with 37% of schools reporting no instruction at any level. Given the prevalence of sleep disorders and the relationship of these disorders to significant underlying medical conditions, a strong case can be made for the formal implementation of a curriculum in sleep and chronobiology in medical education, residency, and beyond.

The effects of midazolam and temazepam on sleep and performance when administered in the middle of the night

A multicenter, double-blind, sleep laboratory and performance study was conducted to evaluate the hypnotic efficacy and residual effects of midazolam (15 mg) and temazepam (30 mg) compared to placebo when administered in the middle of the night. Eighteen volunteers with objectively verified sleep maintenance insomnia received placebo for 3 nights during week 1 (adaptation and screening). During weeks 2, 3, and 4 they received 2 consecutive nights of midazolam, temazepam, and placebo (one treatment per week) in a balanced crossover design. Treatment was administered in the middle of the night (3.5 hours after bedtime). Neither drug reduced the latency to return to sleep after the middle of the night awakening. Both drugs significantly increased total sleep time, reduced wake during sleep, and number of awakenings over 4.5 hours in bed after treatment. In the morning (5 to 6.5 hours postdrug) significant performance decrements and reduced daytime sleep latency (7 hours postdrug) were found with temazepam but not midazolam.