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 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 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).(AU)

Excessive sleepiness: under-recognized and essential marker for sleep/wake disorder management.

BACKGROUND: Research during the past few decades has provided substantial evidence indicating that excessive sleepiness (ES) and associated sleep/wake disorders can result in significant morbidity and mortality. However, symptomatology (e.g., ES) and the relationships among common morbidities (e.g., cardiovascular disease, metabolic disorders, mood impairment) and sleep/wake disorders remain under-recognized in clinical practice, particularly in primary care. Yet assessment of sleep/wakefulness and associated symptoms can often be easily conducted in the primary care setting, providing valuable information to facilitate the diagnosis and management of sleep/wake disorders. OBJECTIVE: To provide a conceptual and educational framework that helps primary care physicians comprehensively assess, differentially diagnosis, and appropriately manage patients presenting with ES or ES-related sleep/wake disorders. METHODS: Comprised of six sleep specialists and six primary care physicians, the Sleep/Wake Disorders Working Group (SWG) used a modified, two-round Delphi approach to create and harmonize consensus recommendations for the assessment, diagnosis, treatment, and ongoing management of patients with common sleep/wake disorders related to ES. RESULTS: After a review of the relevant literature, the SWG arrived at consensus on a number of clinical recommendations for the assessment and management ES and some of the most commonly associated sleep/wake disorders. Ten consensus statements ­ five each for assessment/diagnosis and treatment/ongoing care ­ were created for ES, insomnia, obstructive sleep apnea, circadian rhythm disorders, restless legs syndrome, and narcolepsy. CONCLUSION: ES and ES-related sleep/wake disorders are commonly encountered in the primary care setting. By providing an educational framework for primary care physicians, the SWG hopes to improve patient outcomes by emphasizing recognition, prompt diagnosis, and appropriate ongoing management of ES and associated sleep/wake disorders.

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 mirtazapine's 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.

Evaluation of chronic insomnia. An American Academy of Sleep Medicine review.

Insomnia is a condition which affects millions of individuals, giving rise to emotional distress, daytime fatigue, and loss of productivity. Despite its prevalence, it has received scant clinical attention. An adequate evaluation of persistent insomnia requires detailed historical information as well as medical, psychological and psychiatric assessment. Use of a classification system for sleep disorders and familiarity with major diagnostic groups will facilitate the clinician's evaluation and treatment. Thorough assessment also requires attention to the unique aspects of presentation and specific set of etiologies which are associated with particular age groups.

Sleep in neuropsychiatric disorders.

Sleep disorders have been recognized for millennia as a common complication of medical and neurologic disease. Virtually all neuropsychiatric disorders carry with them the potential for disturbances of sleep. When such complications do exist, they are typically associated with decreased quality of life, increased morbidity, and, in some cases, increased mortality rates. The prevalence of major sleep disorders among neurologic patients is high, but the rate of detection and treatment is quite low. The major sleep-related problems in this population can be divided into six areas: insomnia, circadian rhythm (sleep-wake schedule) disorders, hypersomnia, sleep-related breathing disorders, motor disturbances in sleep, and parasomnias. In this brief review, general clinical principles, diagnostic assessment and management guidelines for each of these areas are considered and their specific manifestations in neuropsychiatric disorders identified.

Obstructive sleep apnea syndrome in a patient with medulloblastoma.

We present one adult patient with medulloblastoma who developed polysomnographically documented obstructive sleep apnea after posterior fossa surgery. The sleep apnea worsened in conjunction with clinical and imaging-confirmed neoplastic progression and clinically improved after craniospinal radiation therapy. Medulloblastoma or its surgical treatment has never before been implicated in a sleep-related breathing disorder. We discuss possible mechanisms for its occurrence and management implications.

Measuring quality of care in psychiatric emergencies: construction and evaluation of a Bayesian index.

OBJECTIVE: This study was conducted to determine whether an index for measuring quality of care for psychiatric emergencies is reliable and valid. DATA SOURCES/STUDY SETTING: The study used primary data collected over a 12-month period from two urban hospitals in the Northeast. One had 700 inpatient beds, an inpatient psychiatric unit, and community mental health personnel located in the emergency department. The other had 300 beds but none of the other hospital's features. STUDY DESIGN: The index was developed by a panel of experts in emergency psychiatry using a subjective Bayesian statistical methodology and was evaluated in terms of its ability to: (1) predict a second panel's judgments of quality; (2) predict a specific quality-related patient outcome, i.e., compliance with follow-up recommendations; (3) provide a reliable measurement procedure; and (4) detect variations in patterns of emergency department practices. DATA COLLECTION/EXTRACTION METHODS: Data were collected on 2,231 randomly selected emergency psychiatric patients (psychiatric diagnosis, alcohol abuse, nonverbal patients experiencing a psychiatric emergency, and patients with somatic complaints such as life crisis) treated in the emergency departments of the two hospitals. PRINCIPAL FINDINGS: The index predicted physician judgments of quality, was reliable, exhibited sufficient variation in scores, and was strongly associated with patient compliance. CONCLUSIONS: The study demonstrated that a subjective Bayesian model can be used to develop a reliable and valid index for measuring quality of care, with potential for practical application in management of health services.

Nocturnal enuresis in children with upper airway obstruction.

This study presents the results of our experience with 115 children between the ages of 3 and 19 years who have had symptoms of upper airway obstruction and nocturnal enuresis. Twelve children had secondary enuresis, and 103 children had primary enuresis. Surgical removal of upper airway obstruction led to a significant decrease in or complete cure of nocturnal enuresis in 87 (76%) of the children studied. Eleven children were also studied with polysomnographic tracings in an attempt to determine a relationship between their sleep patterns and nocturnal enuresis.

Clinical safety of flurazepam and midazolam during 14-day use in chronic insomniacs.

Data from evening questionnaires, reports of side effects, laboratory findings, and all-night respiratory measurements were collected on the 99 chronic insomniacs examined in this multicenter study. These data were used to compare the clinical safety and desirability of a benzodiazepine hypnotic with a very short half-life, midazolam 15 mg, with a hypnotic with a longer half-life, flurazepam 15 and 30 mg; both compounds were compared with a placebo control. There were 2 prestudy placebo nights followed by 14 consecutive nights of treatment. Of the 107 patients accepted, 99 completed the study. No marked adverse reactions were found in any area for any group. There was no increase in sleep apneas during the treatment period for any group. Results of this study provide additional evidence of the safety of benzodiazepine hypnotics.

Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: an introduction.

A review of the published literature reveals many unanswered questions regarding the effects of sedative-hypnotics on sleep, performance, and mood. The relationship between plasma half-life and hypnotic efficacy is also not clear. A randomized, double-blind, parallel-groups, multicenter study was designed to examine sleep, performance, and mood in patients with insomnia. A large, heterogeneous sample of patients with a history of benzodiazepine use for chronic insomnia was chosen to reflect the adult population for which sedative-hypnotics are often prescribed and to ensure statistical reliability. Although the major focus of the current study was on the effects of two benzodiazepine hypnotics on performance, this study also provided information on the following important issues: (1) effect of dose level; (2) short-versus long-term administration; and (3) significance of plasma half-life as it relates to hypnotic efficacy.

Quality assurance for psychiatric emergencies. An analysis of assessment and feedback methodologies.

Improvement in the quality of evaluation and treatment of behavioral emergencies presenting to hospital emergency rooms requires a multicomponent assessment of resources, clinician performance, and outcome. The authors present a summary of data and conclusions derived from index-based assessment of quality of care in over 2000 psychiatric emergencies. The study revealed that emergency room physicians rendered high-quality medical care, but were deficient in crucial aspects of psychiatric evaluation and treatment including evaluation of dangerousness and substance abuse and provision of appropriate follow-up care. A positive association was observed between quality of care and compliance with referral. Subsequent review with the staff pointed to issues such as staffing, emergency room and community resources, and adequacy of documentation as significant influences on quality of care, as assessed by the chart-audit, index approach. A pilot study demonstrated uniform improvement of quality scores in a small group of physicians receiving written and oral feedback about their performance. The use of focused quality assessment studies that examine both structural and process factors, and their correlation with outcome, is discussed in light of the information obtained from the previously described study. A feedback methodology that emphasizes an interactive process to identify deficiencies in care and to explore their causes and remedies is presented.

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.

Response to opioids in three patients with restless legs syndrome.

Three patients with restless legs syndrome, two of whom also had nocturnal myoclonus, responded well to treatment with low doses of opioids. The pathophysiology of the syndrome and the mechanism of opioids' therapeutic action are discussed.

Sleep laboratory and performance evaluation of midazolam in insomniacs.

This study evaluated laboratory sleep and performance after placebo, after 5, 10 and 20 mg of midazolam and after 30 mg of flurazepam. EEG recordings showed that 20 mg of midazolam significantly decreased sleep latency and stage 1 sleep, increased stage 2 sleep, and delayed the onset of the first REM period when compared with placebo. Subjective reports from the patients showed that the dose decreased the frequency of awakenings. In the morning, 9 h after drug ingestion, performance on most tests was affected very little by 20 mg of midazolam. However, performance on two psychomotor tests was slightly impaired after 20 mg of midazolam, while a test of free recall was slightly improved. On most variables, 5 mg of midazolam acted like placebo, while 10 mg of midazolam was intermediate between placebo and 20 mg of midazolam. Preliminary data suggest that 20 mg of midazolam may be as efficacious in inducing sleep as 30 mg of flurazepam, but may show fewer performance decrements in the morning.

Effectiveness of a sleep disorders center: a 9-month follow-up.

To assess the usefulness of a sleep disorders center the authors sent follow-up questionnaires to patients and referring physicians 9 months after each diagnostic evaluation. Findings suggest that sleep disorders centers provide a useful diagnostic service, especially for patients suffering from excessive daytime sleepiness. This problem usually has a medical etiology, and sleep laboratory evaluations seemed crucial for about two-thirds of all such patients. Insomnia was more likely to involve behavioral/psychological factors; about 30% of the patients with long-term, serious insomnia seemed to benefit markedly from the sleep center evaluation.