Comorbid depression in obstructive sleep apnea: an under-recognized association.

BACKGROUND: Obstructive sleep apnea (OSA) and depression may coexist in the same patient. This article aims to review the link between OSA and comorbid depression and critically evaluate the results of studies that assessed the correlation between OSA and depression, the impact of OSA treatment on comorbid depression, and the impact of comorbid depression on continuous positive airway pressure (CPAP) adherence. METHODS: An integrative review was conducted on English language studies and reports that assessed the relationship between OSA and depression. Studies were identified by searching PubMed, Web of Science and Google Scholar databases, and reference lists of included studies. RESULTS: Generally, cross-sectional studies show a higher prevalence of depression among OSA patients with both community and sleep disorder clinic samples. Nevertheless, the relationship between OSA and depression is complicated by the fact that the disorders have overlapping symptoms. Longitudinal studies demonstrate an increased risk of developing depression among people with OSA, as well as an association between OSA severity and the likelihood of developing depression. On the other hand, studies assessing the impact of CPAP therapy on depression among OSA patients report conflicting results. Therefore, it is essential to consider how the disorders affect one another and to understand the clinical consequences of treating each disorder in isolation. CONCLUSION: Depression is prevalent among patients with OSA both in the community and in sleep disorder clinics. Clinicians in general should be aware of this significant association and should aim to treat both disorders.

New and emerging pharmacotherapeutic approaches for insomnia.

Advances in understanding the neurochemistry of sleep and waking have stimulated new pharmacological directions in the treatment of insomnia. While the sedation of historic insomnia medications was discovered serendipitously, now compounds can be developed for specific molecular targets with known sleep-related actions. Numerous investigational compounds, including some entirely novel approaches, are being evaluated currently as possible insomnia treatments. In recent years the US Federal Drug Administration (FDA) has approved medications with new pharmacodynamic and pharmacokinetic properties thereby extending the options for personalized pharmacotherapy. The FDA is reviewing new applications for innovative sleep-promoting medications currently, including suvorexant and tasimelteon. Presently the FDA-approved insomnia treatment medications include benzodiazepine receptor agonists available in immediate-release, extended-release, and alternative delivery oral absorption formulations; a melatonin receptor agonist; and a histamine receptor antagonist. Clinical indications include insomnia associated with difficulty with sleep onset, sleep maintenance, and middle-of-the-night awakenings. Alternative approaches to treating insomnia have included prescription medications employed on an off-label basis for insomnia, over-the-counter sleep aids, and assorted unregulated substances marketed to enhance sleep.

Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia.

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1-2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.

Chronic insomnia.

Chronic insomnia afflicts millions of people in the United States. It is associated with decreased quality of life, accidents, several comorbid conditions, increased morbidity, and substantial direct and indirect costs. Chronic insomnia is a multifactorial and individualized disorder. Its etiology may be cognitive or physiologic in nature (or both), and is more often than not associated with a comorbid condition, complicating its recognition, evaluation, and treatment. Effective nonpharmacotherapeutic (cognitive-behavioral therapy for insomnia) and pharmacotherapeutic (hypnotic medications) treatment modalities are available. Treatment of chronic insomnia can make a significant improvement in quality of life, and may also be associated with an improvement in comorbid conditions.

Sleep disturbance in heavy marijuana users.

STUDY OBJECTIVE: To determine if recently abstinent, heavy marijuana (MJ) users show differences in polysomnographic (PSG) measures compared with a drug-free control group. DESIGN: A group of carefully selected heavy MJ users were chosen for study inclusion and matched to a drug-free control group. Questionnaire data were collected prior to cessation of MJ use. PSG studies were conducted during 2 consecutive nights after discontinuation of MJ use in our core sleep laboratory. SETTING: Baltimore Maryland, General Clinical Research Center (GCRC) core sleep lab. PARTICIPANTS: 17 heavy MJ users discontinuing MJ use and 14 drug-free controls. Men and women were studied, 18 to 30 years. The MJ users reported no other drug use and alcohol use was negligible in both groups. Urine was positive for metabolites of cannabis only. MEASUREMENTS AND RESULTS: The MJ users showed differences in PSG measures (lower total sleep times, and less slow wave sleep than the control group) on both nights; they also showed worse sleep efficiency, longer sleep onset, and shorter REM latency than the control group on Night 2. More sleep continuity parameters were significantly worse for the MJ group than the control group on Night 2 versus Night 1, indicating that sleep in the MJ group was relatively worse on Night 2 compared to Night 1. The MJ group did not show improved sleep after an adaptation night as expected. Withdrawal symptoms, craving, and depression did not appear to influence these findings. CONCLUSIONS: During discontinuation of heavy MJ use, PSG measures of sleep disturbance were detected in MJ users compared with a drug-free control group. While this preliminary study cannot identify the extent to which these group differences were present before abstinence, poor sleep quality either prior to or after MJ discontinuation could result in treatment failure for MJ users. Further investigation is necessary to determine the association between the use and cessation of MJ and sleep disturbance.

Pharmacotherapy of Insomnia.

Insomnia remains a common clinical concern that is associated with negative daytime consequences for patients and represents a significant public health problem for our society. Although a variety of therapies may be employed to treat insomnia, the use of medications has been a dominant approach. Regulatory agencies have now classified insomnia medications into 4 distinct pharmacodynamics classes. Medications with indications approved for insomnia treatment include benzodiazepine receptor agonists, a melatonin receptor agonist, a selective histamine receptor antagonist, and a dual orexin/hypocretin receptor antagonist. Both pharmacodynamic and pharmacokinetic advances with hypnotic medications in recent years have expanded the pharmacopoeia to allow personalized treatment approaches for different patient populations and individual sleep disturbance patterns.

Chronic Insomnia Disorder.

PURPOSE OF REVIEW: Neurologists, along with all health care providers, commonly encounter patients with insomnia, which is a condition that impacts patients' underlying neurologic conditions in a bidirectional manner. While chronic insomnia is one of the most common sleep disturbances, only a small proportion of individuals with this condition discuss their sleep problems with their providers. When insomnia is described, it is more often in relationship to another medical problem, as opposed to an independent condition. In neurology practice, multiple factors including pain, movement disorders, sleep apnea, and medications that act on the central nervous system often contribute to insomnia. An all-inclusive approach is necessary when evaluating sleep problems in patients with insomnia. RECENT FINDINGS: The US Food and Drug Administration (FDA) has approved several medications for the treatment of insomnia that target specific receptor systems in the brain and incorporate several unique pharmacodynamic and pharmacokinetic profiles that can represent customized therapy for specific insomnia phenotypes. FDA-approved medications for insomnia include γ-aminobutyric acid (GABA)-modulating benzodiazepine receptor agonists, a melatonin receptor agonist, a histamine receptor antagonist, and the newest approved option, a hypocretin (orexin) receptor antagonist. SUMMARY: This article provides an evidence-based multidisciplinary approach to the treatment of insomnia, highlighting the rationale and utility of cognitive-behavioral therapy and pharmacologic interventions. Neurologists should be proactive in assessing the impact of underlying comorbidities on insomnia, particularly in the setting of psychiatric conditions such as depression, sleep disorders such as circadian rhythm disorders, and medical problems such as nocturia.

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).

Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders.

Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by persistent or recurrent patterns of sleep disturbance related primarily to alterations of the circadian rhythm system or the misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. These disorders collectively represent a significant unmet medical need, with a total prevalence in the millions, a substantial negative impact on quality of life, and a lack of studied treatments for most of these disorders. Activation of the endogenous melatonin receptors appears to play an important role in setting the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore, melatonin agonists, which may be able to shift and/or stabilize the circadian phase, have been identified as potential therapeutic candidates for the treatment of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is approved for the treatment of a CRSWD: non-24-hour sleep-wake disorder (or non-24). However, three additional commercially available melatonin receptor agonists-agomelatine, prolonged-release melatonin, and ramelteon-have been investigated for potential use for treatment of CRSWDs. Data indicate that these melatonin receptor agonists have distinct pharmacologic profiles that may help clarify their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic properties of these melatonin agonists and summarize their efficacy profiles when used for the treatment of CRSWDs. Further studies are needed to determine the therapeutic potential of these melatonin agonists for most CRSWDs.

Insomnia.

Insomnia is a common problem that is chronic for many individuals. Multiple processes, including psychologic, physiologic, and environmental factors, can influence insomnia, and their effects can shift over time. Accordingly, the evaluation of patients who have insomnia should be broad in scope. Insomnia represents a clinical problem with significant daytime consequences, associations, and comorbidities. Several nosologies categorize insomnia into specific diagnoses. Useful minimal criteria for an insomnia disorder include persistent nighttime symptoms with daytime distress or impairment. Specific treatments, addressing particular underlying causes,and general pharmacologic and nonpharmacologic strategies may play valuable roles in the management of insomnia patients. The effective treatment of insomnia can have further benefits in decreasing the likelihood of future psychiatric symptoms.

National Sleep Foundation's updated sleep duration recommendations: final report.

OBJECTIVE: To make scientifically sound and practical recommendations for daily sleep duration across the life span. METHODS: The National Sleep Foundation convened a multidisciplinary expert panel (Panel) with broad representation from leading stakeholder organizations. The Panel evaluated the latest scientific evidence and participated in a formal consensus and voting process. Then, the RAND/UCLA Appropriateness Method was used to formulate sleep duration recommendations. RESULTS: The Panel made sleep duration recommendations for 9 age groups. Sleep duration ranges, expressed as hours of sleep per day, were designated as recommended, may be appropriate, or not recommended. Recommended sleep durations are as follows: 14-17 hours for newborns, 12-15 hours for infants, 11-14 hours for toddlers, 10-13 hours for preschoolers, 9-11 hours for school-aged children, and 8-10 hours for teenagers. Seven to 9 hours is recommended for young adults and adults, and 7-8 hours of sleep is recommended for older adults. The self-designated basis for duration selection and critical discussions are also provided. CONCLUSIONS: Consensus for sleep duration recommendations was reached for specific age groupings. Consensus using a multidisciplinary expert Panel lends robust credibility to the results. Finally, limitations and caveats of these recommendations are discussed.

National Sleep Foundation's sleep time duration recommendations: methodology and results summary.

OBJECTIVE: The objective was to conduct a scientifically rigorous update to the National Sleep Foundation's sleep duration recommendations. METHODS: The National Sleep Foundation convened an 18-member multidisciplinary expert panel, representing 12 stakeholder organizations, to evaluate scientific literature concerning sleep duration recommendations. We determined expert recommendations for sufficient sleep durations across the lifespan using the RAND/UCLA Appropriateness Method. RESULTS: The panel agreed that, for healthy individuals with normal sleep, the appropriate sleep duration for newborns is between 14 and 17 hours, infants between 12 and 15 hours, toddlers between 11 and 14 hours, preschoolers between 10 and 13 hours, and school-aged children between 9 and 11 hours. For teenagers, 8 to 10 hours was considered appropriate, 7 to 9 hours for young adults and adults, and 7 to 8 hours of sleep for older adults. CONCLUSIONS: Sufficient sleep duration requirements vary across the lifespan and from person to person. The recommendations reported here represent guidelines for healthy individuals and those not suffering from a sleep disorder. Sleep durations outside the recommended range may be appropriate, but deviating far from the normal range is rare. Individuals who habitually sleep outside the normal range may be exhibiting signs or symptoms of serious health problems or, if done volitionally, may be compromising their health and well-being.

The association between daytime sleepiness and sleep-disordered breathing in NREM and REM sleep.

BACKGROUND: Daytime sleepiness is common in patients with sleep-disordered breathing. Although respiratory events during sleep are associated with the occurrence of daytime sleepiness, the differential impact of these events during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep on daytime sleepiness has not been well characterized. STUDY OBJECTIVES: To determine the effect of respiratory events during REM sleep and NREM sleep on daytime sleepiness, as assessed by the multiple sleep latency test (MSLT). DESIGN: Cross-sectional study. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: Patients referred for polysomnography and daytime MSLT (n=1,821). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The study sample was initially divided into quartiles based on the level of the apnea-hypopnea index (AHI) during NREM sleep. Within the first NREM-AHI quartile (NREM-AHI < 8.3 events/hr), the association between REM-related respiratory events and daytime sleepiness was examined using the method of Kaplan-Meier analysis and Cox proportional hazards regression. After adjusting for age, gender, body mass index, and the duration of NREM and REM sleep, REM-AHI was not associated with daytime sleepiness (Relative Risk: 1.01; 95%CI: 0.94-1.10). Similarly, no significant association was observed between REM-AHI and the MSLT in patients within the second through fourth NREM-AHI quartiles. In contrast, increasing severity of disordered breathing during NREM sleep was associated with daytime sleepiness. For a 10-point increase in NREM-AHI, the adjusted relative risks for daytime sleepiness in the second through fourth NREM-AHI quartile were 1.21 (95%CI: 1.01-1.46), 1.20 (95%CI: 1.05-1.37), and 1.10 (95%CI: 1.04-1.16), respectively. CONCLUSION: Sleep-disordered breathing during NREM sleep, but not REM sleep, is associated with increased risk of daytime sleepiness.

Chronic insomnia: current issues.

Insomnia is a common problem in the general population and has a higher prevalence in persons with medical and psychiatric disorders. Although insomnia is most often transient, occurring as a result of identifiable stressors, a substantial portion of insomnia cases involve persistent sleep difficulty. This chronic form of insomnia may be associated with a wide range of adverse consequences. An understanding of the characteristics and causes of this disorder and the available therapeutic strategies will promote more effective identification and treatment of patients with chronic insomnia.

Pharmacologic approaches for the treatment of chronic insomnia.

Insomnia is a common problem that for many sufferers persists chronically and may result from a wide range of causes. Specific treatments address particular underlying medical disorders. General therapeutic approaches, including pharmacologic and behavioral strategies, may have broad applicability to insomnia patients. Many different medications and substances have been used in an attempt to improve sleep. This article reviews the advantages and disadvantages of medications and other substances employed to promote improved sleep. Special emphasis is given to the use of the newer-generation benzodiazepine receptor agonist hypnotics.

Cognitive behavior therapy for chronic insomnia.

Approximately 20% of patients presenting in general medical settings have severe and persistent insomnia. Studies consistently find that trouble initiating and maintaining sleep are independent risk factors for medical and psychiatric morbidity, but insomnia is often underdetected and undertreated in primary care settings. Cognitive-behavioral treatment approaches for chronic insomnia and related sleep disorders have been shown to be effective in various patient populations. This article reviews the most common cognitive-behavioral interventions for insomnia, and discusses their efficacy and durability. Possible adaptations for the integration of these approaches into primary care settings and a description of the emerging field of behavioral sleep medicine as a resource for health care providers treating patients with chronic insomnia are also presented.

Chronic insomnia.

PURPOSE OF REVIEW: This article provides an overview of current strategies for evaluating and treating patients who experience chronic insomnia. RECENT FINDINGS: The US Food and Drug Administration (FDA) has approved several medications for the treatment of insomnia that incorporate a variety of pharmacodynamic and pharmacokinetic properties, thus allowing the development of a customized therapeutic approach. FDA-approved medications include γ-aminobutyric acid-modulating benzodiazepine receptor agonists, a melatonin receptor agonist, and a histamine receptor agonist. Psychological and behavioral techniques combined as cognitive-behavioral therapy also have been shown to be effective in the treatment of chronic insomnia. SUMMARY: Insomnia is the most common sleep disturbance and represents a chronic condition for many people. Difficulty falling asleep and maintaining sleep are highly prevalent problems in patients with neurologic disorders. Multiple factors typically contribute to insomnia. Accordingly, a rather broad approach to evaluating patients is warranted. Evidence-based guidelines support the use of cognitive and behavioral strategies and selected medications in the treatment of patients with chronic insomnia.