Sleep Initiation and Maintenance Disorders: Krystal AD

Krystal AD. · No affiliation provided · Sleep. · Pubmed #15700715 No free full text.

This publication has no abstract.

Krystal AD. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. · J Clin Sleep Med. · Pubmed #17557457 No free full text.

Abstract: STUDY OBJECTIVES: Impairments in health, function, and quality of life (QOL) are a central feature of insomnia, yet insomnia treatment is targeted solely to improving problems falling and staying asleep. It is not even known if the nonsleep deficits improve with current treatment. We hypothesized that therapy that improves sleep also improves these nonsleep difficulties and carried out this review to test that hypothesis. METHODS: A literature search identified the health, function, and QOL deficits of insomnia patients. A second search determined the effect of insomnia treatments on those problems, capturing randomized controlled treatment trials in insomnia patients that included relevant measures. RESULTS: Insomnia patients report a variety of symptoms, including daytime sleepiness, fatigue, cognitive impairment, symptoms of depression, anxiety, health decrements, and impairment in social and occupational function. However, the reported deficits are generally not paralleled by objective evidence of impairment. Nineteen treatment studies reported measures related to these deficits. At least one treatment (eszopiclone [5 studies], zopiclone [2 studies], progressive muscle relaxation [2], zolpidem [2], multi-component cognitive-behavioral therapy [1], doxepin [1], valerian/hops [1], and stimulus control [1]) led to a significant improvement compared with placebo in at least one of these measures in 14/20 studies. CONCLUSIONS: Treatment can improve the perceived health, function, and QOL of insomnia patients. This potential improvement signals the need to shift the attention of research and clinical practice to include aspects other than sleep difficulties and move towards defining successful therapy as not only improving sleep but also eliminating deficits in health, function, and QOL.

Krystal AD. · Sleep Research Laboratory and Insomnia Program, Duke University Medical Center, Durham, North Carolina 22710, USA. · J Am Geriatr Soc. · Pubmed #15982374 No free full text.

Abstract: There is a need for newer, more clinically useful classifications for insomnia. Identification of specific subtypes of insomnia helps anchor research, allows for prediction of prognosis/course of the condition, and may allow for individualization of treatment. Existing classifications differ, and many terms remain inadequately defined, which leads to diagnostic confusion. Historically, insomnia has been classified according to symptom type, symptom duration, and underlying cause, but these classifications have not been based on evidence of their utility, and newer research suggests the need for change. Symptoms may include difficulty falling asleep, trouble staying asleep, and not feeling restored by sleep, although it has not been clear that it is possible to identify distinct subtypes of patients by symptom or that distinguishing symptom type affects the course of clinical treatment. Classification of insomnia by duration most commonly involves three categories: transient (no more than a few days), short-term (up to 3 weeks), and long-term (more than 3 weeks). This categorization is of uncertain utility and has been primarily based on nonempiric concerns about treatment with sedative-hypnotic medications for periods longer than several weeks. The subtyping of insomnia in terms of whether there is an identifiable underlying cause such as a psychiatric or medical illness was based on an unproven assumption that in most instances other disorders caused insomnia. Recent studies suggest the need to revisit these classification strategies. Evidence that symptom types typically overlap and change over time complicates the categorization of subjects by whether they have difficulty falling asleep or staying asleep or have nonrestorative sleep. New studies of the treatment of chronic insomnia change the perspective on duration of treatment and, as a result, classification of duration of disease. Two studies of nightly pharmacotherapy for insomnia including more than 800 insomnia patients have not identified any increase in the risks after 3 to 4 weeks of treatment. In addition, nonpharmacological treatments demonstrate long-lasting efficacy in patients with chronic insomnia, and the development of abbreviated cognitive-behavioral therapies, which are particularly well suited to primary care practice, have improved their applicability. Newer studies of the relationships between insomnia and associated medical and psychiatric conditions undermine the notion that insomnia is always a symptom and caused by an underlying condition. They suggest that, although it is important to identify and treat these conditions, this may not be sufficient to alleviate the insomnia, which may adversely affect the course of the associated disorder. As a result, treatment targeted specifically to the insomnia should be considered. All of these developments point to an increasing ability to tailor therapy to the particular needs of patients and to optimize the clinical management of insomnia.

Krystal AD. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA. · Clin Cornerstone. · Pubmed #15457812 No free full text.

Abstract: Depression and insomnia are both significantly more prevalent in women than in men. Risks appear linked to fluctuations and transitions in gonadal hormones during various phases of women's lives, with the risk of depression greatest during the period from menarche to menopause. Increased risks of both insomnia and depression also coincide with the late luteal phase of the menstrual cycle, during and after pregnancy, and during the peri-/postmenopausal period. Gonadal hormones exert significant effects on the neurohumoral systems most intimately associated with depression and insomnia, with corresponding implications for treatment. Medications related to the serotonin system-the selective serotonin reuptake inhibitors, or SSRIs-appear to be uniquely effective in the treatment of insomnia and depression experienced by women. SSRIs and the nonbenzodiazepine receptor agonists are generally useful as first-line treatments in a number of circumstances; hormone replacement therapies can also be considered. Behavioral therapies for insomnia may be particularly relevant for postpartum patients because of safety concerns and to prevent the development of autonomous chronic insomnia, which may also increase the risk of depression. In light of the high risk of relapse and high likelihood of comorbidity, it is crucial to effectively treat both insomnia and depression in women. However, few data exist for many key areas related to the treatment of these disorders in women, and research is greatly needed.

Krystal AD. · Duke University Medical Center, Durham, NC, USA. · J Clin Psychiatry. · Pubmed #15153064 No free full text.

Abstract: A particular challenge in the treatment of insomnia is management of chronic insomnia, which occurs in a substantial portion of the population. A number of factors suggest the importance of identifying this condition as distinct from short-term insomnia in clinical practice and treating these 2 entities differently. Yet, there is no consensus about how to make this distinction or how to manage patients beyond the short term. Clinicians have been without guidance as to how to address the significant challenges associated with treating patients long term with any of the currently available treatments. In recent years, however, new studies have suggested the emergence of a changing perspective on the management of chronic insomnia. These studies have begun to provide an empirical basis for making decisions in the treatment of patients with chronic insomnia. They suggest that clinical practice is evolving toward an improved capacity to treat insomnia, with treatments that can safely lead to sustained efficacy.

Krystal AD. · Sleep Research Laboratory, Duke University Medical Center, Durham, North Carolina, USA. · Clin Cornerstone. · Pubmed #14626540 No free full text.

Abstract: Insomnia is a highly prevalent disorder that can lead to substantial impairments in quality of life and functional capacity. This condition occurs significantly more frequently in women than men. An important contributing factor is that insomnia can occur in association with hormonal changes that are unique to women, such as those of menopause or the late-luteal phase of the menstrual cycle. Another consideration is that women are more likely to suffer from major depression and anxiety disorders, which are also associated with insomnia. The reasons are unclear as are the reasons why women are at increased risk of primary insomnia. These conditions are frequently encountered in clinical practice and present a challenge to the practitioner because there is a striking lack of research data to serve as a guide. For example, there are no published studies to indicate how to safely and effectively manage insomnia that often occurs late in pregnancy. This article reviews the available literature related to these conditions with a focus on the epidemiologic data and diagnosis and treatment of insomnia and highlights the need for further research.

Edinger JD, Krystal AD. · VA Medical Centers, Durham, NC, USA. · Sleep Med Rev. · Pubmed #12927120 No free full text.

Abstract: Among the range of primary insomnia subtypes, those assigned such labels as subjective insomnia or sleep state misperception historically have been among the most intriguing yet challenging to understand and manage clinically. Such patients who produce seemingly normal polysomnograms often present rather compelling and, at times, dramatic sleep complaints. Our earliest formal sleep nosology included a separate diagnostic category for such individuals, but little research has been devoted to this insomnia subtype in the 20 years since this classification scheme was proposed. As a result, use of diagnoses such as subjective insomnia or sleep state misperception have remained controversial. The current article reviews this controversy and highlights the major criticisms forged against subdividing primary insomnia into objective and subjective subtypes. Subsequently, the relative merits of these criticisms are considered in view of early and recent findings vis-à-vis the subjective/objective insomnia dichotomy. Although available data are not conclusive, there appears to be sufficient evidence to suggest subjective and objective insomnia subtypes may suffer from distinctive forms of sleep-related pathophysiology. We conclude by advocating continued study of the subjective insomnia phenomenon and by providing specific directions for relevant future research.

Perlis ML, McCall WV, Krystal AD, Walsh JK. · Sleep and Neurophysiology Laboratory, Department of Psychiatry, University of Rochester, and the University of Rochester Medical Center, Neurosciences Program, Rochester, NY 14642, USA. · J Clin Psychiatry. · Pubmed #15323600 No free full text.

Abstract: INTRODUCTION: While it is common practice that hypnotics are used on a non-nightly basis, few investigations have been undertaken to evaluate the efficacy of the intermittent dosing strategy. The present study was designed to further evaluate this issue within a large scale, double-blind, placebo-controlled, long-term trial. METHOD: Patients who met DSM-IV criteria for primary insomnia participated in the study from January 2000 through October 2001. Patients were randomly assigned to 1 of 2 treatment groups (zolpidem 10 mg or placebo) for a period of 12 weeks. Ten pills were provided in foil packs on an every-other-week basis, and patients were instructed to take no fewer than 3 and no more than 5 pills per week. Sleep was evaluated daily with sleep diaries. Pill use was recorded in the sleep diaries. RESULTS: 199 patients (mean +/- SD age = 41.0 +/- 12.8 years; 71% female) were randomly assigned to treatment. On mean, patients receiving zolpidem exhibited (vs. baseline) a 42% decrease in sleep latency, a 52% reduction in number of awakenings, a 55% decrease in wake time after sleep onset, and a 27% increase in total sleep time. These positive clinical gains did not diminish with time and were not associated with dose escalation. There was also no evidence of rebound insomnia. CONCLUSIONS: Over a period of 12 weeks of intermittent treatment with zolpidem, sleep continuity was significantly improved, the clinical gains were sustained, and there was no evidence of subjective rebound insomnia between doses or increases in the amount of medication used during the study interval.

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.

Krystal AD, Edinger JD, Wohlgemuth WK, Marsh GR. · · Sleep. · Pubmed #12224842 No free full text.

Abstract: STUDY OBJECTIVES: To determine whether the frequency spectrum of the sleep EEG is a physiologic correlate of 1) the degree to which individuals with persistent primary insomnia (PPI) underestimate their sleep time compared with the traditionally scored polysomnogram (PSG) and 2) the sleep complaints in PPI subjects who have relatively long traditionally scored PSG sleep times and relatively greater underestimation of sleep time. DESIGN: We compared EEG frequency spectra from REM and NREM sleep in PPI subjects subtyped as subjective insomnia sufferers (those with relatively long total sleep time and relative underestimation of sleep time compared with PSG), and objective insomnia sufferers (those with relatively short PSG total sleep time) with EEG frequency spectra in normals. We also studied the correlation between these indices and the degree of underestimation of sleep. Further, we determined the degree to which sleep EEG indexes related to sleep complaints. SETTING: Duke University Medical Center Sleep Laboratory. PARTICIPANTS: Normal (N=20), subjective insomnia (N=12), and objective insomnia (N=18) subjects. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Lower delta and greater alpha, sigma, and beta NREM EEG activity were found in the patients with subjective insomnia but not those with objective insomnia, compared with the normal subjects. These results were robust to changes in the subtyping criteria. No effects were found for REM spectral indexes. Less delta non- REM EEG activity predicted greater deviation between subjective and PSG estimates of sleep time across all subjects. For the subjective insomnia subjects, diminished low-frequency and elevated higher frequency non- REM EEG activity was associated with their sleep complaints. CONCLUSIONS: NREM EEG frequency spectral indexes appear to be physiologic correlates of sleep complaints in patients with subjective insomnia and may reflect heightened arousal during sleep.

Carney CE, Ulmer C, Edinger JD, Krystal AD, Knauss F. · Department of Psychology, Ryerson University, 350 Victoria Street, JOR1037, Toronto, Ontario, Canada. · J Psychiatr Res. · Pubmed #18954876 No free full text.

Abstract: BACKGROUND: Due to concerns about overlapping symptomatology between medical conditions and depression, the validity of the beck depression inventory (BDI-II) has been assessed in various medical populations. Although major depressive disorder (MDD) and primary insomnia (PI) share some daytime symptoms, the BDI-II has not been evaluated for use with insomnia patients. METHOD: Participants (N=140) were screened for the presence of insomnia using the Duke structured clinical interview for sleep disorders (DSISD), and evaluated for diagnosis of MDD using the structured clinical interview for DSM-IV-TR (SCID). Participants' mean BDI-II item responses were compared across two groups [insomnia with or without MDD) using multivariate analysis of variance (MANOVA), and the accuracy rates of suggested clinical cutoffs for the BDI-II were evaluated using a receiver operating characteristic (ROC) curve analysis. RESULTS: The insomnia with depression group had significantly higher scores on several items; however, the groups did not differ on insomnia, fatigue, concentration problems, irritability, libido, increased appetite, and thoughts relating to suicide, self-criticism and punishment items. The ROC curve analysis revealed moderate accuracy for the BDI-II's identification of depression in those with insomnia. The suggested BDI cutoff of >or=17 had 81% sensitivity and 79% specificity. Use of the mild cutoff for depression (>or=14) had high sensitivity (91%) but poor specificity (66%). CONCLUSION: Several items on the BDI-II might reflect sleep disturbance symptoms rather than depression per se. The recommended BDI-II cutoffs in this population have some support but a lower cutoff could result in an overclassification of depression in insomnia patients, a documented problem in the clinical literature. Understanding which items discriminate insomnia patients without depression may help address this nosological issue.

Edinger JD, Means MK, Carney CE, Krystal AD. · VA Medical Center, Durham, NC 27705, USA. · Sleep. · Pubmed #18517030 links to  free full text

Abstract: OBJECTIVE: To examine psychomotor (reaction time) performance deficits and their relation to subjective and objective sleep measures among individuals with primary insomnia (PI). DESIGN AND SETTING: This study was conducted at affiliated VA and academic medical centers using a matched-groups, cross-sectional research design. PARTICIPANTS: Seventy-nine (43 women) individuals with PI (MAge = 50.0 +/- 17.1 y) and 84 (41 women) well-screened normal sleepers (MAge = 48.6 +/- 16.8 y). METHODS AND MEASURES: Participants underwent 3 nights of polysomnography (PSG) followed by daytime testing with a 4-trial multiple sleep latency test (MSLT). Before each MSLT nap, they rated their sleepiness and completed a performance battery that included simple reaction time (SRT), continuous performance (CPT), and 4 switching attention (SAT) tests. Performance measures included the mean response latency and the standard deviation of each subject's within-test response latencies. RESULTS: PI sufferers reported greater (P = 0.001) daytime sleepiness, but were significantly (P = 0.02), more alert than normal sleepers on the MSLT. Multivariate analyses showed the PI group had significantly longer response latencies and greater response variability across many of the subtests than did the controls. Regression analyses showed that both PSG- and diary-based sleep measures contributed to the prediction of daytime performance indices, although objective wake time after sleep onset appeared the best single predictor of the daytime measures. CONCLUSIONS: Results confirm that PI sufferers do show relative psychomotor performance deficits when responding to challenging reaction time tasks, and these deficits appear related to both objective and subjective sleep deficits. Findings support PI patients' diurnal complaints and suggest the usefulness of complex reaction time tasks for assessing them.

Krystal AD, Erman M, Zammit GK, Soubrane C, Roth T, Anonymous00063. · Duke University Medical Center, Durham, NC 27710, USA. · Sleep. · Pubmed #18220081 links to  free full text

Abstract: STUDY OBJECTIVES: To evaluate long-term efficacy and safety of zolpidem extended-release 3 to 7 nights/week for chronic primary insomnia. DESIGN: Multicenter, 25-week, phase IIIb, randomized, double-blind, placebo-controlled, parallel-group. SETTING: Outpatient; visits every 4 weeks. PATIENTS: Aged 18 to 64 years; DSM-IV criteria for chronic primary insomnia; > or =3 months of difficulty initiating or maintaining sleep or experiencing nonrestorative sleep. INTERVENTIONS: Single-dose zolpidem extended-release 12.5 mg (n = 669) or placebo (n = 349), self-administered from a minimum of 3 nights/week to a maximum of 7 nights/week. MEASUREMENTS AND RESULTS: Patient's Global Impression (PGI) and Clinical Global Impression-Improvement (CGI-I) were assessed every 4 weeks up to week 24. Patient Morning Questionnaire (PMQ), recorded daily, assessed subjective sleep measures-sleep onset latency (SOL), total sleep time (TST), number of awakenings (NAW), wake time after sleep onset (WASO), and quality of sleep (QOS)-and next-day functioning. At week 12, PGI, Item 1 (aid to sleep), the primary endpoint, was scored as favorable (i.e., "helped me sleep") by 89.8% of zolpidem patients vs. 51.4% of placebo patients (P < 0.0001, based on rank score) and at week 24 by 92.3% of zolpidem extended-release patients vs. 59.7% of placebo patients. Zolpidem extended-release also was statistically significantly superior to placebo at every time point for PGI (Items 1-4) and CGI-I (P < 0.0001, rank score), TST, WASO, QOS (P < 0.0001), and SOL (P < or = 0.0014); NAW (Months 2-6; P < 0.0001). Sustained improvement (P < 0.0001, all time points) was observed in morning sleepiness and ability to concentrate (P = 0.0014, month 6) with zolpidem extended-release compared with placebo. Most frequent adverse events for zolpidem extended-release were headache, anxiety and somnolence. No rebound effect was observed during the first 3 nights of discontinuation. CONCLUSIONS: These findings establish the efficacy of 3 to 7 nights per week dosing of zolpidem extended-release 12.5 mg for up to 6 months. Treatment provided sustained and significant improvements in sleep onset and maintenance and also improved next-day concentration and morning sleepiness.

Walsh JK, Krystal AD, Amato DA, Rubens R, Caron J, Wessel TC, Schaefer K, Roach J, Wallenstein G, Roth T. · Sleep Medicine and Research Center, St. John's/St. Luke's Hospitals and the Department of Psychology, Saint Louis University, St. Louis, MO 63017, USA. · Sleep. · Pubmed #17702264 links to  free full text

Abstract: STUDY OBJECTIVES: To evaluate 6 months' eszopiclone treatment upon patient-reported sleep, fatigue and sleepiness, insomnia severity, quality of life, and work limitations. DESIGN: Randomized, double blind, controlled clinical trial. SETTING: 54 research sites in the U.S. PATIENTS: 830 primary insomnia patients who reported mean nightly total sleep time (TST) < or = 6.5 hours/night and/or mean nightly sleep latency (SL) >30 min. INTERVENTION: Eszopiclone 3 mg or matching placebo. MEASUREMENTS: Patient-reported sleep measures, Insomnia Severity Index, Medical Outcomes Study Short-Form Health Survey (SF-36), Work Limitations Questionnaire, and other assessments measured during baseline, treatment Months 1-6, and 2 weeks following discontinuation of treatment. RESULTS: Patient-reported sleep and daytime function were improved more with eszopiclone than with placebo at all months (P <0.001). Eszopiclone reduced Insomnia Severity Index scores to below clinically meaningful levels for 50% of patients (vs 19% with placebo; P <0.05) at Month 6. SF-36 domains of Physical Functioning, Vitality, and Social Functioning were improved with eszopiclone vs placebo for the Month 1-6 average (P < 0.05). Similarly, improvements were observed for all domains of the Work Limitations Questionnaire with eszopiclone vs placebo for the Month 1-6 average (P <0.05). CONCLUSIONS: This is the first placebo-controlled investigation to demonstrate that long-term nightly pharmacologic treatment of primary insomnia with any hypnotic enhanced quality of life, reduced work limitations, and reduced global insomnia severity, in addition to improving patient-reported sleep variables.

Wohlgemuth WK, Krystal AD. · Sleep Research Laboratory and Insomnia Program, Duke University Medical Center, Durham, NC 27710, USA. · J Clin Sleep Med. · Pubmed #17561623 No free full text.

This publication has no abstract.

Carney CE, Segal ZV, Edinger JD, Krystal AD. · Duke Insomnia and Sleep Research Program, Duke University Medical Center, Durham, NC 27710, USA. · J Clin Psychiatry. · Pubmed #17335324 No free full text.

Abstract: OBJECTIVE: A number of pharmacologic studies have documented that insomnia is among the most commonly reported residual symptoms after remission from depression. Residual symptoms after remission are particularly relevant because these symptoms confer greater risk for subsequent depression. This study was the first to date to examine residual insomnia after cognitive-behavioral therapy (CBT) for depression and to compare CBT with pharmacotherapy for depression on residual insomnia rates. METHOD: This naturalistic study examined rates of posttreatment insomnia complaints in patients (N = 94) who had been diagnosed with major depressive disorder (MDD), according to DSM-IV criteria, and who remitted from MDD after completing at least 20 weeks of either CBT or pharmacotherapy at an outpatient clinic specializing in mood disorders. Participants were randomly assigned to the treatment conditions, but only the data from those who completed treatment and remitted were analyzed. Primary outcome measure was the 17-item Hamilton Rating Scale for Depression. Data were collected from October 1, 1999, to September 23, 2003. Groups were compared using a chi(2) for nominal data. RESULTS: The rate of posttreatment insomnia was 22% for sleep-onset insomnia, 26% for sleep-maintenance insomnia, and 17% for early morning awakenings, and the rates did not statistically differ across the 2 treatment groups. CONCLUSION: Although CBT and pharmacotherapy effectively addressed depression in these patients and addressed insomnia symptoms for many, there were a number of patients with residual insomnia. Whereas there appears to be no difference between CBT and pharmacotherapy with regard to rates of residual insomnia, the rates of such insomnia remaining after these treatments suggest that adjunctive sleep treatment to specifically address insomnia may be necessary for some MDD patients.

McCall WV, Erman M, Krystal AD, Rosenberg R, Scharf M, Zammit GK, Wessel T. · Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA. · Curr Med Res Opin. · Pubmed #16968566 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and efficacy of eszopiclone 2 mg in elderly patients (aged 64-86 years) with chronic insomnia. METHODS: This was a randomized, double-blind, placebo-controlled 2-week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] >or= 20 min and latency to persistent sleep >or= 20 min) were randomized to 2 weeks of nightly treatment with eszopiclone 2 mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography (Nights 1, 2, 13, and 14) and patient reports (Nights 1-14); safety was assessed using adverse events, clinical labs, physical examination, and vital signs. The mean of all efficacy results during the double-blind period was used for the efficacy analysis. RESULTS: Results indicated that eszopiclone was associated with significantly shorter sleep onset, less WASO, higher sleep efficiency, more total sleep time, and greater patient-reported quality and depth of sleep scores than placebo (p < 0.05 for all) with a trend in patient-reported morning sleepiness (p = 0.07). Other measures of daytime functioning (ability to function, daytime alertness, and sense of well-being) were not significantly different between the two treatment groups. Among patients who napped, eszopiclone patients reported fewer naps (p = 0.03) and less cumulative naptime (median: 98 min placebo, 70 min eszopiclone, p = 0.07). Unpleasant taste, dry mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively). CONCLUSION: In this study, eszopiclone was well tolerated and produced significant improvements in both polysomnographic and patient-reported measures of sleep maintenance, sleep induction, and sleep duration in elderly patients with chronic primary insomnia.

Edinger JD, Wohlgemuth WK, Krystal AD, Rice JR. · Psychology Service, Veterans Affairs Medical Center, Durham, NC 27705, USA. · Arch Intern Med. · Pubmed #16314551 links to  free full text

Abstract: BACKGROUND: Insomnia is common and debilitating to fibromyalgia (FM) patients. Cognitive-behavioral therapy (CBT) is effective for many types of patients with insomnia, but has yet to be tested with FM patients. This study compared CBT with an alternate behavioral therapy and usual care for improving sleep and other FM symptoms. METHODS: This randomized clinical trial enrolled 47 FM patients with chronic insomnia complaints. The study compared CBT, sleep hygiene (SH) instructions, and usual FM care alone. Outcome measures were subjective (sleep logs) and objective (actigraphy) total sleep time, sleep efficiency, total wake time, sleep latency, wake time after sleep onset, and questionnaire measures of global insomnia symptoms, pain, mood, and quality of life. RESULTS: Forty-two patients completed baseline and continued into treatment. Sleep logs showed CBT-treated patients achieved nearly a 50% reduction in their nocturnal wake time by study completion, whereas SH therapy- and usual care-treated patients achieved only 20% and 3.5% reductions on this measure, respectively. In addition, 8 (57%) of 14 CBT recipients met strict subjective sleep improvement criteria by the end of treatment compared with 2 (17%) of 12 SH therapy recipients and 0% of the usual care group. Comparable findings were noted for similar actigraphic improvement criteria. The SH therapy patients showed favorable outcomes on measures of pain and mental well-being. This finding was most notable in an SH therapy subgroup that self-elected to implement selected CBT strategies. CONCLUSIONS: Cognitive-behavioral therapy represents a promising intervention for sleep disturbance in FM patients. Larger clinical trials of this intervention with FM patients seem warranted.

Ancoli-Israel S, Benca RM, Edinger JD, Krystal AD, Mendelson W, Moldofsky H, Petrie J, Roth T, Walsh JK, Winkelman J, Anonymous00109. · No affiliation provided · J Clin Psychiatry. · Pubmed #15153067 No free full text.

This publication has no abstract.

Krystal AD, Roth T. · Duke University Medical Center, Durham, NC, USA. · J Clin Psychiatry. · Pubmed #15153061 No free full text.

This publication has no abstract.

Roth T, Krystal AD, Lieberman JA. · Sleep Disorders and Research Center, Henry Ford Health System, Detroit, MI, USA. · CNS Spectr. · Pubmed #17603408 links to  free full text

Abstract: Insomnia is a disorder characterized by chronic sleep disturbance associated with daytime disability or distress, such as memory impairment and fatigue, that occurs despite adequate opportunity for sleep. Insomnia may present as difficulty falling/staying asleep or as sleep that is nonrestorative. Studies show a strong correlation between insomnia and impaired quality of life. Pain conditions and depression are commonly associated with insomnia, either as secondary or comorbid conditions. In addition, a greater incidence of anxiety, alcohol and drug dependence, and cardiovascular disease is found in people with insomnia. Data indicate insomnia results from over-engaged arousal systems. Insomnia patients experience increased metabolic rate, body temperature, and heart rate, and elevated levels of norepinephrine and catecholamines. Pharmacologic options for the treatment of insomnia include benzodiazepine hypnotics, a selective melatonin receptor agonist, and sedating antidepressants. However, insomnia may be best treated with cognitive-behavioral therapy and instruction in good sleep hygiene, either alone or in concert with pharmacologic agents. Studies on the effects of insomnia treatment use variable methodologies or do not publish negative results, and there are currently no studies of treatment focusing on morbidity. Further research is necessary to better understand the effects of insomnia therapies on medical and psychiatric disorders. In this Clinical Information Supplement, Thomas Roth, PhD, describes the nature of insomnia and its pathophysiology. Next, Andrew D. Krystal, MD, MS, reviews morbidities associated with insomnia. Finally, Joseph A. Lieberman III, MD, MPH, provides an overview of therapeutics utilized in patients with insomnia, including behavioral therapies and pharmacologic options.