Sleep Initiation and Maintenance Disorders: Roth T

Roth T. · No affiliation provided · Sleep Med. · Pubmed #18346676 No free full text.

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Roth T. · No affiliation provided · Sleep Med. · Pubmed #18032105 No free full text.

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Roth T, Drake C. · No affiliation provided · Sleep. · Pubmed #16676773 No free full text.

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Roth T. · Henry Ford Hospital Sleep Disorders and Research Center, 2799 W Grand Blvd, Detroit, MI 48202, USA. · Am J Manag Care. · Pubmed #19298104 links to  free full text

Abstract: Insomnia is a leading cause of absenteeism, presenteeism (lost productivity when employees are at work), accidents, and errors in the workplace. Overall direct and indirect costs exceed $30 billion annually. A significant portion of these costs are attributable to patients with comorbid insomnia, making these conditions a significant clinical public health issue. These comorbid conditions include mood and anxiety disorders; chronic pain; respiratory, urinary, and neurologic conditions; diabetes; and cardiovascular diseases. Traditional treatment for insomnia with comorbid conditions has focused on treating the comorbid condition with the expectation that the insomnia will resolve. Recent studies, however, suggest this approach is not the most appropriate. Instead, treating both conditions simultaneously may improve the outcomes for each.

Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, 2799 West Grand Boulevard, CFP-3 Detroit, MI 48202, USA. · Sleep Med. · Pubmed #18693067 No free full text.

Abstract: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality and morbidity worldwide. Because of the chronic nature of the disease, optimal care for patients includes successful treatment of comorbidities that accompany COPD, including insomnia. Insomnia symptoms and associated disruption of sleep are prevalent in COPD patients but treatment with traditional benzodiazepines may compromise respiratory function. This review summarizes the efficacy and safety consideration of current drugs available for the treatment of insomnia in COPD patients including benzodiazepines, non-benzodiazepine receptor agonists such as eszopiclone, zolpidem, and zaleplon, sedating antidepressants such as trazodone, and the melatonin receptor agonist ramelteon.

Roth T, Franklin M, Bramley TJ. · Xcenda, 1528 Preston St, Salt Lake City, UT 84108, USA. · Am J Manag Care. · Pubmed #18041871 links to  free full text

Abstract: Recent research into the pathophysiology of insomnia has brought a shift in the approach to treatment. Insomnia rarely occurs in isolation and is typically comorbid with other conditions. Rather than simply treating the primary disorder, whereby symptoms of insomnia may go unaddressed, now there is a push to acknowledge the existence of chronic insomnia as a disorder that itself merits treatment. This recognition is due to the identification of pathophysiologic changes and associated morbidity, which can be substantial. Insomnia patients have increased risk for psychiatric disorders, especially depression, anxiety, decreased quality of life, increased healthcare utilization and costs, drug/alcohol abuse, decreased occupational performance, and increased falls/accidents. Current management patterns explore non-nightly or discontinuous hypnotic treatment - non-nightly flexible, non-nightly semiflexible, non-nightly fixed, and flexible timing - which deviates from past trends of continuous dosing with hypnotics. These trends reflect a change from considering insomnia a symptom to treating insomnia as a disorder.

Roth T. · Sleep Disorders and Research Center at Henry Ford Health System, Henry Ford Hospital Sleep Center, 2799 West Grand Blvd., Detroit, MI 48202, USA. · J Clin Sleep Med. · Pubmed #17824495 links to  free full text

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Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI 48202, USA. · J Clin Psychiatry. · Pubmed #17539704 No free full text.

Abstract: Insomnia is a highly prevalent disorder with consequences for the patient's physical and mental health, daily function, and job performance. Although the exact pathophysiology of insomnia is unknown, recent research has demonstrated that normal sleep and wakefulness are controlled by reciprocal inhibition by different brain regions. This sleep-wake control system offers multiple therapeutic targets for the treatment of insomnia; currently, most research and available hypnotic agents target gamma-aminobutyric acid (GABA) on the sleep side of the switch. Historically, drugs have evolved from benzodiazepine receptor agonists to nonbenzodiazepines to, most recently, selective extrasynaptic GABA(A) receptor agonists. However, these drugs have a differential impact on characteristics of sleep. Among the compounds that modulate the benzodiazepine-sensitive GABA(A) receptors, benzodiazepines suppress stage 3-4 sleep, whereas nonbenzodiazepines have no substantial effect on these stages of sleep. Recently, work on GABA agonists indicates that they increase stage 3-4 sleep. This has been demonstrated via sleep-stage scoring as well as with spectral analysis. Further, this increase in stage 3-4 sleep is associated with a decrease in stage 1 sleep and arousals from sleep. Thus, the GABA agonists may not simply promote sleep, but consolidate it as well. The clinical utility of the increase in slow-wave sleep and the sleep consolidation it produces warrants further investigation.

Roth T, Roehrs T, Pies R. · Sleep Disorders and Research Center, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. · Sleep Med Rev. · Pubmed #17175184 No free full text.

Abstract: Interest in developing a greater understanding of the pathophysiogical mechanisms underlying primary insomnia has increased. Recent evidence indicates that there may be some neuroendocrine and clinical similarities between primary insomnia and major depressive disorder, that abnormal corticotropin releasing factor (CRF) activity occurs in major depression, and that CRF hyperactivity appears to mediate the hyperarousal seen in primary insomnia. These findings all point to the possibility of hypothalamic-pituitary-adrenal (HPA) axis and CRF overactivity in both disorders. More recent findings have strengthened the evidence that primary insomnia may be linked with mood disorders and is associated with HPA axis overactivity and excess secretion of CRF, adrenocorticotropin releasing hormone, and cortisol. These insights have implications for managing chronic primary insomnia, such as use of antiglucocorticoid agents.

Roth T. · Henry Ford Hospital Sleep Center, Detroit, MI 48202, USA. · J Clin Psychiatry. · Pubmed #16336036 No free full text.

Abstract: Insomnia, the most commonly reported sleep problem, affects about one third of the adult American population. Insomnia impairs the individual's functioning, diminishes his or her quality of life, and contributes to accidents, health care costs, and problems at work. Insomnia is frequently comorbid with physical and mental illness, as either a consequence or a contributing factor. In particular, considerable research supports a strong association between insomnia and depression. Because the majority of individuals who have trouble sleeping attempt to treat the problem independently using over-the-counter medications or alcohol, insomnia is undertreated by health care providers, despite its serious consequences.

Roth T, Drake C. · Sleep Disorders Centre, Department of Psychiatry and Behavioral Neurosciences, Henry Ford Hospital, Detroit, MI 48202, USA. · Sleep Med. · Pubmed #15301994 No free full text.

Abstract: Traditional epidemiologic studies of insomnia provide valid but fairly rudimentary information regarding the presence, frequency, duration and evolution of sleep problems. Standardized tools such as validated questionnaires (e.g., Pittsburgh Sleep Quality Index and sleep logs) help assess the presence and severity of sleep problems, while other methods (e.g., SLEEP L system) address insomnia diagnoses. Other instruments (e.g., Structured Clinical Interview for DSM-IV [SCID], Short-Form 36 [SF-36], Epworth Sleepiness Scale [ESS]) provide insights into insomnia consequences and co-morbidities. Sleep laboratory studies using polysomnography (PSG) have also provided useful findings (e.g., relating to sleep apnea and excessive daytime sleepiness) in experimental and population-based patient samples containing subgroups enriched for certain variables under investigation. These methods have significantly increased our knowledge about insomnia. Critically, longitudinal studies are needed to further our understanding of the pathophysiology and morbidity of insomnia, defining roles for risk factors, hyperarousal and co-morbidities and the effects of treatment in long-term disease progression. This review summarizes the current available data on the evolution of insomnia and proposes a model that warrants further research attention and discussion.

Roth T. · Henry Ford Hospital Sleep Center, Detroit, MI, USA. · J Clin Psychiatry. · Pubmed #15153062 No free full text.

Abstract: The measurement of insomnia treatment efficacy has evolved over time. Historically, patient report measures were used to assess sleep the previous night, and, although important, these measures were not objectively validated. While the advent of polysomnography complemented patient reports of nocturnal sleep, few studies have evaluated daytime functioning and impact of impaired sleep on comorbid medical and psychiatric illnesses as measures of the efficacy of hypnotics. In the future, therapeutic endpoints will focus on important factors associated with insomnia, such as enhanced alertness, improved outcomes associated with augmentation therapy for depression, reduction in pain severity, and decreased sleep disturbances associated with hot flashes.

Drake CL, Roehrs T, Roth T. · Henry Ford Hospital Sleep Disorders and Research Center, CFP3, Detroit, Michigan 48202, USA. · Depress Anxiety. · Pubmed #14661186 No free full text.

Abstract: There is growing interest in insomnia both from the perspective of recent advances in clinical management as well as research aimed at elucidating its pathophysiology. This theoretical overview of insomnia describes the negative impact, etiological considerations, and pharmacological and behavioral treatments for the disorder, with an emphasis on areas receiving increased research attention. Insomnia, the most prevalent sleep disorder, affects 10-15% of the general population. In population-based studies severe insomnia has been shown to last for a median of 4 years. In addition, insomnia has a significant negative impact on an individual's work, physical, and social performance as well as overall quality of life. Furthermore, the economic cost of insomnia related to lost productivity, work-related accidents, absenteeism, and health-care costs are enormous. There is increasing evidence linking the precipitation of insomnia to stress, and converging evidence from cognitive, endocrine, neurological, and behavioral domains provide clear evidence for hyper-arousal in insomnia. However, there remains no consensus regarding the specific etiological mechanisms of this disorder. Although the pathophysiology of primary insomnia remains an enigma, numerous treatments both pharmacological and behavioral have been developed and found to be efficacious in controlled studies. Despite the wide availability of pharmacological treatments and increased knowledge of behavioral interventions, the vast majority of individuals with insomnia do not appear to be receiving adequate treatment. The inadequate treatment of insomnia leads to several important and under-recognized consequences including subsequent development of psychiatric disease and increased substance use.

Roth T, Roehrs T. · Division of Sleep Medicine, Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, Michigan, USA. · Clin Cornerstone. · Pubmed #14626537 No free full text.

Abstract: Insomnia is a symptom of difficulty initiating and maintaining sleep or experiencing nonrefreshing sleep and is associated with daytime consequences. Although insomnia is typically secondary to a medical, psychiatric, circadian, or sleep disorder, it can also be a primary disorder. Primary insomnia is estimated to occur in 25% of all chronic insomnia patients. It is hypothesized to be a disorder of hyperarousal, which has been supported by research on the autonomic nervous system and hypothalamic-pituitary-adrenal axis function. Chronic insomnia is prevalent in 10% of the adult population. Age, sex, medical and psychiatric disease, and shift work all represent an increased risk of chronic insomnia. The morbidity of insomnia varies as a function of etiology. While transient insomnia produces sleepiness and impairment in psychomotor performance, chronic insomnia is associated with absenteeism, frequent accidents, memory impairment, and greater health care utilization. The most consistent impact of insomnia is a high risk of depression.

Roehrs T, Roth T. · Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA. · Curr Neurol Neurosci Rep. · Pubmed #12583849 No free full text.

Abstract: This update reviews recent developments and advances in the therapeutic and side-effect profile of the benzodiazepine receptor agonists (BZRAs), the generally accepted drug class of choice for the symptomatic treatment of insomnia. All the approved BZRAs, depending on their pharmacokinetic profile, improve and maintain sleep. The major recent advance is in the enhanced diversity of the pharmacokinetic profiles of these drugs, and thus in the flexibility available to the clinician in treatment strategy. Also, during the past decade the nature and significance of the side effects associated with the BZRAs and their determinants, dose and half-life, have been identified and clarified. The important remaining question is whether, and how, the efficacy and safety of the BZRAs change with chronic use.

Richardson GS, Roth T, Kramer JA. · Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI, USA. · MedGenMed. · Pubmed #11965211 links to  free full text

Abstract: CONTEXT: Insomnia is the most frequently reported sleep symptom, severely affecting up to 15% of the US population. The need to effectively treat this disorder is underscored by the significant adverse consequences on the productivity, safety, overall health, and quality of life of the affected individual. Pharmacologic intervention has traditionally involved the use of benzodiazepine receptor agonists (BzRAs), for which efficacy and general safety have been established. OBJECTIVE: The purpose of this paper is to examine the potentially unique role of zaleplon in the treatment of insomnia. DATA SOURCE: The clinical experience of the authors was critically applied to peer-reviewed published papers or abstracts regarding zaleplon, which were identified via MEDLINE (1995-September 2000). RESULTS: Adverse effects, usually related to residual sedation, impose limits on the use of older BzRAs and have prompted the development of new sleep medications with advantageous adverse event profiles. Zaleplon demonstrates a very rapid onset and offset of effect that permits symptomatic rather than prophylactic administration, resulting in comparable efficacy and reduced risk of the adverse effects associated with longer half-life agents. CONCLUSIONS: The characteristics of zaleplon may translate into distinct and significant clinical advances in the treatment of insomnia.

Richardson GS, Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, Mich 48202, USA. · J Clin Psychiatry. · Pubmed #11388590 No free full text.

Abstract: Research on insomnia has provided a number of important new insights, but fundamental deficits in our understanding remain. In considering priorities for future research, 3 areas warrant immediate attention. First, a causal relationship between insomnia and the adverse outcomes seen in insomnia patients needs to be established. Second, currently available symptomatic therapies need to be optimized. Recent data suggest that some benzodiazepine receptor agonists produce their hypnotic effect without side effects that were presumed to be inherent to sedation. Understanding the neuropharmacology underlying this differential effect would allow substantial improvements in the risk-benefit ratio for these drugs. Finally, the mechanisms of insomnia need to be better understood. Several lines of evidence suggest that physiologic arousal is important to the clinical presentation of primary insomnia. It remains unclear, however, whether this activation is primary or secondary to the insomnia itself. If physiologic hyperarousal causes primary insomnia, it would provide new approaches to the management of this disorder.

Roth T. · Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, Michigan, USA. · Int J Clin Pract Suppl. · Pubmed #11219330 No free full text.

Abstract: Sleep difficulties affect about one-third of American adults, yet these symptoms are not often addressed by patients and their physicians. Unresolved insomnia that impairs daytime function may be associated with significant psychiatric morbidity, predominantly major depression. Clinicians who are aware that these disorders frequently co-exist will be able to facilitate prompt diagnosis and initiate appropriate pharmacotherapeutic intervention. Antidepressant therapies may interfere with sleep quality; therefore, the management of insomnia in depressed patients should be addressed separately. Traditionally, benzodiazepines have been prescribed to treat sleep disturbances, but certain drugs in this class have limited benefits due to residual sedative effects that impair cognitive function, memory and general daytime performance. Zaleplon, a new, quick-acting, non-benzodiazepine sleep medication, may be clinically advantageous in promoting sleep without residual impairment.

Roth T, Hajak G, Ustün TB. · Sleep Disorders and Research Center, Henry Ford Hospital CFP-3, 2799 West Grand Boulevard, Detroit, MI 48202, USA. · Int J Clin Pract. · Pubmed #11219318 No free full text.

Abstract: Insomnia, a common symptom throughout the world, is characterised by difficulty initiating or maintaining sleep or non-restorative sleep and is associated with significant morbidity. A comprehensive medical and sleep history and physical examination are necessary before treating patients with insomnia; the presence of co-morbidities, including medical and psychiatric disorders, or the possible use of substances that may contribute to sleeplessness should be thoroughly investigated. Non-pharmacological approaches include correction of sleep hygiene as well as behavioural treatments. Pharmacotherapy includes benzodiazepine-receptor agonists, which are the drugs of choice for this disorder. They can be subdivided into classic benzodiazepines and non-benzodiazepines. Although many agents in these classes have been prescribed, potential shortcomings include residual sedation, rebound insomnia, and psychomotor and memory impairment. Novel pharmacological strategies that address limitations of the traditional treatment approach, combined with proven modes of behavioural therapy, offer the most successful results in the management of insomnia. These advances provide the opportunity to establish these current recommendations for the optimal management of insomnia. This report from the XXII Collegium Internationale Neuro-Psychopharmacologicum Consensus Workshop outlines recommendations to serve as the foundation for developing a therapeutic plan for each patient.

Roth T. · Division of Sleep Medicine, Henry Ford Hospital, Detroit, Michigan, USA. · Clin Cornerstone. · Pubmed #10875044 No free full text.

Abstract: Insomnia is a significant public health issue. Good sleep is essential for emotional and physical wellbeing. The importance of adequate sleep is evidenced by the fact that insomnia can adversely affect physical and mental health. The National Heart, Lung, and Blood Institute Working Group on Insomnia defines insomnia as an experience of inadequate or poor-quality sleep characterized by one or more of the following: difficulty falling asleep, difficulty maintaining sleep, waking up too early in the morning, or unrefreshing sleep. The symptoms of insomnia also include daytime consequences such as tiredness, lack of energy, difficulty concentrating, or irritability. Insomnia can be a symptom of an underlying medical, psychiatric, sleep, or circadian disorder or a disorder in itself (i.e., primary insomnia). This paper will present information about the prevalence, morbidity, causes, and diagnoses of insomnia, and the behavioral and pharmacologic management of this disorder.

Roth T. · Henry Ford Hospital, Sleep Disorders and Research Center, Detroit, Michigan 48202, USA. · J Psychopharmacol. · Pubmed #10667459 No free full text.

Abstract: Pharmacological management of insomnia is continually evolving. The introduction of non-benzodiazepine benzodiazepine receptor agonist hypnotics provides an opportunity to understand different patterns of pharmacological activity with mechanistic differences in receptor activity. The impact of insomnia on daytime functioning and long-term health and socioeconomic status has been recognized. Epidemiological studies indicate that insomnia is associated with increased absenteeism and healthcare costs (although the latter appear to be partly attributable to comorbid depression). It will thus be important to determine whether hypnotics, in addition to their effects on sleep, provide other benefits for the patient that are related to these parameters. The successful resolution of this issue will require the adoption of additional outcome measures, such as effects on quality of life and healthcare costs. Recognition that long-term hypnotic use is widespread among insomniacs has prompted proposals for alternative prescribing patterns. Although certain hypnotics appear to be free of tolerance on prolonged use, caution is required in the long-term use of any hypnotic because of the lack of systematic data on chronic efficacy and safety. Therefore, alternative administration schedules (e.g. intermittent and 'as required') are being investigated. These may have very different consequences in terms of abuse liability and patients' perceptions of efficacy, and thus permit a more effective and appropriate use of this drug class.

Rajaratnam SM, Polymeropoulos MH, Fisher DM, Roth T, Scott C, Birznieks G, Klerman EB. · Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA. · Lancet. · Pubmed #19054552 No free full text.

Abstract: BACKGROUND: Circadian rhythm sleep disorders are common causes of insomnia for millions of individuals. We did a phase II study to establish efficacy and physiological mechanism, and a phase III study to confirm efficacy of the melatonin agonist tasimelteon (VEC-162) for treatment of transient insomnia associated with shifted sleep and wake time. METHODS: We undertook phase II and phase III randomised, double-blind, placebo-controlled, parallel-group studies. In a phase II study, 39 healthy individuals from two US sites were randomly assigned to tasimelteon (10 [n=9], 20 [n=8], 50 [n=7], or 100 mg [n=7]) or placebo (n=8). We monitored individuals for 7 nights: 3 at baseline, 3 after a 5-h advance of sleep-wake schedule with treatment before sleep, and 1 after treatment; we measured plasma melatonin concentration for circadian phase assessment. In a phase III study, 411 healthy individuals from 19 US sites, who had transient insomnia induced in a sleep clinic by a 5-h advance of the sleep-wake schedule and a first-night effect in a sleep clinic, were given tasimelteon (20 [n=100], 50 [n=102], or 100 mg [n=106]) or placebo (n=103) 30 min before bedtime. Prespecified primary efficacy outcomes were polysomnographic sleep efficiency (phase II study), latency to persistent sleep (phase III study), and circadian phase shifting (phase II study). Analysis was by intention to treat. Safety was assessed in both studies. These trials are registered with ClinicalTrials.gov, numbers NCT00490945 and NCT00291187. FINDINGS: In the phase II study, tasimelteon reduced sleep latency and increased sleep efficiency compared with placebo. The shift in plasma melatonin rhythm to an earlier hour was dose dependent. In the phase III study, tasimelteon improved sleep latency, sleep efficiency, and wake after sleep onset (ie, sleep maintenance). The frequency of adverse events was similar between tasimelteon and placebo. INTERPRETATION: After an abrupt advance in sleep time, tasimelteon improved sleep initiation and maintenance concurrently with a shift in endogenous circadian rhythms. Tasimelteon may have therapeutic potential for transient insomnia in circadian rhythm sleep disorders.

Zammit GK, McNabb LJ, Caron J, Amato DA, Roth T. · Columbia University College of Physicians and Surgeons, New York 10025, USA. · Curr Med Res Opin. · Pubmed #15701215 No free full text.

Abstract: OBJECTIVE: Eszopiclone is a new, single-isomer, non-benzodiazepine, cyclopyrrolone agent under investigation for the treatment of insomnia. The present study was a randomized, double-blind, multicenter, placebo-controlled trial conducted to assess the efficacy and safety of eszopiclone in adults with chronic primary insomnia. RESEARCH DESIGN AND METHODS: Patients (n = 308) were randomized to receive placebo or eszopiclone (2 mg or 3 mg) for 44 consecutive nights, followed by 2 nights of single-blind placebo. Efficacy was evaluated with polysomnography (Nights 1, 15 and 29) and patient-reports (Nights 1, 15, 29 and 43/44). Next-day residual effects were evaluated using the Digit-Symbol Substitution Test (DSST). RESULTS: Eszopiclone 3 mg had significantly less time to sleep onset (p < or = 0.0001), more total sleep time and sleep efficiency (p < or = 0.0001), better sleep maintenance (p < or = 0.01), and enhanced quality and depth of sleep (p < 0.05) across the double-blind period compared with placebo. Eszopiclone 2 mg had significantly less time to sleep onset (p < or = 0.001), more total sleep time (p < or = 0.01) and sleep efficiency (p < or = 0.001), and enhanced quality and depth of sleep (p < 0.05) compared with placebo, but did not significantly improve sleep maintenance. There was no evidence of tolerance or rebound insomnia after therapy discontinuation. Median DSST scores showed no decrement in psychomotor performance relative to baseline and did not differ from placebo in either eszopiclone group. Treatment was well tolerated; the most common adverse event related to eszopiclone was unpleasant taste. CONCLUSIONS: Patients treated with nightly eszopiclone 3 mg had better polysomnographic (through Night 29) and patient-reported measures (through Night 44) of sleep over the 6-week trial. There was no evidence of tolerance or rebound insomnia and no detrimental effects on next-day psychomotor performance using the DSST.

Rosenberg R, Caron J, Roth T, Amato D. · Northside Hospital Sleep Medicine Institute, 5780 Peachtree Dunwoody Road, Suite 150, Atlanta, GA 30342, USA. · Sleep Med. · Pubmed #15680290 No free full text.

Abstract: BACKGROUND AND PURPOSE: This randomized, double-blind, placebo-controlled study assessed the efficacy and safety of eszopiclone, a non-benzodiazepine hypnotic agent, in healthy adults using the first-night effect model of transient insomnia. PATIENTS AND METHODS: A total of 436 healthy, normal sleeping participants were randomized to receive either eszopiclone 1, 2, 3, or 3.5mg, or placebo. Efficacy and next-morning effects were evaluated via polysomnography (PSG), Digit Symbol Substitution Test (DSST), and self-report. RESULTS: Patients treated with eszopiclone had significantly less PSG latency to persistent sleep (all doses except 1mg; P< or =0.0001), wake time after sleep onset (all doses; P< or =0.05) and number of awakenings (3 and 3.5mg doses; P<0.005), and greater sleep efficiency (all doses; P< or =0.02) compared with placebo. Self-reported efficacy results were similar to PSG. Self-reported morning sleepiness scores were significantly better for eszopiclone 3 and 3.5mg compared with placebo (P<0.05). Treatment was well tolerated by patients, and the most common treatment-related adverse event was unpleasant taste. CONCLUSIONS: In this model of transient insomnia, all doses of eszopiclone were more effective than placebo and were well tolerated by patients.

Krystal AD, Walsh JK, Laska E, Caron J, Amato DA, Wessel TC, Roth T. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. · Sleep. · Pubmed #14655910 No free full text.

Abstract: STUDY OBJECTIVES: To determine the long-term efficacy of eszopiclone in patients with chronic insomnia. DESIGN: Randomized, double-blind, multicenter, placebo-controlled. SETTING: Out-patient, with monthly visits. PATIENTS: Aged 21 to 69 years meeting DSM IV criteria for primary insomnia and reporting less than 6.5 hours of sleep per night, and/or a sleep latency of more than 30 minutes each night for at least 1 month before screening. INTERVENTIONS: Eszopiclone 3 mg (n = 593) or placebo (n = 195), nightly for 6 months MEASUREMENTS AND RESULTS: Efficacy was evaluated weekly using an interactive voice-response system. Endpoints included sleep latency; total sleep time; number of awakenings; wake time after sleep onset; quality of sleep; and next-day ratings of ability to function, daytime alertness, and sense of physical well-being. At the first week and each month for the study duration, eszopiclone produced significant and sustained improvements in sleep latency, wake time after sleep onset, number of awakenings, number of nights awakened per week, total sleep time, and quality of sleep compared with placebo (P < or = 0.003). Monthly ratings of next-day function, alertness, and sense of physical well-being were also significantly better with the use of eszopiclone than with placebo (P < or = 0.002). There was no evidence of tolerance, and the most common adverse events were unpleasant taste and headache. CONCLUSIONS: Throughout 6 months, eszopiclone improved all of the components of insomnia as defined by DSM-IV, including patient ratings of daytime function. This placebo-controlled study of eszopiclone provides compelling evidence that long-term pharmacologic treatment of insomnia is efficacious.