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Andrew D Krystal

Publications and source records attributed to Andrew D Krystal.

16 recordsLinked to original sources

Sleep and psychiatric disorders: future directions.

Understanding of the relationship between co-occurring sleep and psychiatric disorders has undergone a radical change. The longstanding perspective that sleep problems invariably are a symptom of a psychiatric disorder is giving way to understanding that complex bidirectional relationships may exist. This change has opened doors to new directions in research and led to changes in guidelines for clinical practice. This article discusses promising future directions for building on this foundation, including developing lines of research currently underway, studying mechanisms that underlie the relationships between sleep and psychiatric disorders; and developing treatment strategies that target these mechanisms to lead to better treatment of sleep disorders and psychiatric disorders.

Comorbidity↗

A polysomnography study of eszopiclone in elderly patients with insomnia.

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.

Aged↗

Behavioral insomnia therapy for fibromyalgia patients: a randomized clinical trial.

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.

Adult↗

The effect of insomnia definitions, terminology, and classifications on clinical practice.

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.

Humans↗

Depression and insomnia in women.

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.

Adult↗

Long-term, non-nightly administration of zolpidem in the treatment of patients with primary insomnia.

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.

Adolescent↗

The changing perspective on chronic insomnia management.

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.

Antidepressive Agents↗

Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia.

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.

Adult↗

Insomnia in women.

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.

Anxiety Disorders↗

Subtyping primary insomnia: is sleep state misperception a distinct clinical entity?

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.

Diagnosis, Differential↗

Comparison of seizure duration, ictal EEG, and cognitive effects of ketamine and methohexital anesthesia with ECT.

The authors retrospectively compared the seizure duration, ictal EEG, and cognitive side effects of ketamine and methohexital anesthesia with ECT. This comparison was carried out with data from consecutive index ECT treatments that occurred immediately before and after a switch from methohexital to ketamine in 36 patients. Ketamine was well tolerated and prolonged seizure duration overall, but particularly in those who had a seizure duration shorter than 25 seconds with methohexital at the maximum available stimulus intensity. Ketamine also increased midictal EEG slow-wave amplitude. Thus, a switch to ketamine may be useful when it is difficult to elicit a robust seizure. Faster post-treatment reorientation with ketamine may suggest a lower level of associated cognitive side effects.

Aged↗

NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes.

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.

Adult↗