Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Sleep Initiation and Maintenance Disorders: HELP
Articles by Dr. Andrew Krystal
Based on 50 articles published since 2009
(Why 50 articles?)
||||

Between 2009 and 2019, A. Krystal wrote the following 50 articles about Sleep Initiation and Maintenance Disorders.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. 2017

Sateia, Michael J / Buysse, Daniel J / Krystal, Andrew D / Neubauer, David N / Heald, Jonathan L. ·Geisel School of Medicine at Dartmouth, Hanover, NH. · University of Pittsburgh School of Medicine, Pittsburgh, PA. · University of California, San Francisco, San Francisco, CA. · Johns Hopkins University School of Medicine, Baltimore, MD. · American Academy of Sleep Medicine, Darien, IL. ·J Clin Sleep Med · Pubmed #27998379.

ABSTRACT: INTRODUCTION: The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults. METHODS: The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations. RECOMMENDATIONS: The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of evidence in published data. Downgrading the quality of evidence for these treatments is predictable in GRADE, due to the funding source for most pharmacological clinical trials and the attendant risk of publication bias; the relatively small number of eligible trials for each individual agent; and the observed heterogeneity in the data. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. We suggest that clinicians use suvorexant as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use eszopiclone as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zaleplon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zolpidem as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use triazolam as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use temazepam as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use ramelteon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use doxepin as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tiagabine as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use diphenhydramine as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use melatonin as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tryptophan as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use valerian as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK).

2 Review Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA. 2017

McCall, W Vaughn / Benca, Ruth M / Rosenquist, Peter B / Riley, Mary Anne / McCloud, Laryssa / Newman, Jill C / Case, Doug / Rumble, Meredith / Krystal, Andrew D. ·From the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta; the Department of Psychiatry and Human Behavior, University of California, Irvine; the Department of Biostatistical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, N.C.; the Department of Psychiatry, University of Wisconsin, Madison; and the Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, N.C. ·Am J Psychiatry · Pubmed #27609243.

ABSTRACT: OBJECTIVE: Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. METHOD: This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. RESULTS: Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. CONCLUSIONS: The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

3 Review Recognizing and managing insomnia in primary care and specialty settings. 2016

Krystal, Andrew D / Sorscher, Adam J. · ·J Clin Psychiatry · Pubmed #27137433.

ABSTRACT: Insomnia is a common feature of both medical and psychiatric disorders. Whether as a symptom of an illness or as a comorbid disorder, insomnia worsens patient outcomes related to quality of life, functioning, workplace productivity, and health care expenditures. This CME webcast covers how to screen for insomnia in patients with both medical and mental illnesses and how to develop a comprehensive treatment plan. The authors also review evidence-based therapies for insomnia, including psychological/behavioral interventions and medications.

4 Review Insomnia disorder. 2015

Morin, Charles M / Drake, Christopher L / Harvey, Allison G / Krystal, Andrew D / Manber, Rachel / Riemann, Dieter / Spiegelhalder, Kai. ·Université Laval, École de psychologie, 2325 rue des Bibliothèques, Québec City, Québec G1V 0A6, Canada. · Henry Ford Hospital Sleep Disorders and Research Center, Detroit, Michigan, USA. · Department of Psychology, University of California, Berkeley, Berkeley, California, USA. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina, USA. · Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA. · Department of Clinical Psychology and Psychophysiology/Sleep Medicine, Center for Mental Disorders, University of Freiburg Medical Center, Freiburg, Germany. ·Nat Rev Dis Primers · Pubmed #27189779.

ABSTRACT: Insomnia disorder affects a large proportion of the population on a situational, recurrent or chronic basis and is among the most common complaints in medical practice. The disorder is predominantly characterized by dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep, along with substantial distress and impairments of daytime functioning. It can present as the chief complaint or, more often, co-occurs with other medical or psychiatric disorders, such as pain and depression. Persistent insomnia has been linked with adverse long-term health outcomes, including diminished quality of life and physical and psychological morbidity. Despite its high prevalence and burden, the aetiology and pathophysiology of insomnia is poorly understood. In the past decade, important changes in classification and diagnostic paradigms have instigated a move from a purely symptom-based conceptualization to the recognition of insomnia as a disorder in its own right. These changes have been paralleled by key advances in therapy, with generic pharmacological and psychological interventions being increasingly replaced by approaches that have sleep-specific and insomnia-specific therapeutic targets. Psychological and pharmacological therapies effectively reduce the time it takes to fall asleep and the time spent awake after sleep onset, and produce a modest increase in total sleep time; these are outcomes that correlate with improvements in daytime functioning. Despite this progress, several challenges remain, including the need to improve our knowledge of the mechanisms that underlie insomnia and to develop more cost-effective, efficient and accessible therapies.

5 Review New Developments in Insomnia Medications of Relevance to Mental Health Disorders. 2015

Krystal, Andrew D. ·Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC 27705, USA. Electronic address: andrew.krystal@duke.edu. ·Psychiatr Clin North Am · Pubmed #26600112.

ABSTRACT: Many insomnia medications with high specificity have become available recently. They provide a window into the clinical effects of modulating specific brain systems and establish a new guiding principal for conceptualizing insomnia medications: "mechanism matters." A new paradigm for insomnia therapy in which specific drugs are selected to target the specific type of sleep difficulty for each patient includes administering specific treatments for patients with insomnia comorbid with particular psychiatric disorders. This article reviews insomnia medications and discusses the implications for optimizing the treatment of insomnia occurring comorbid with psychiatric conditions.

6 Review Current, emerging, and newly available insomnia medications. 2015

Krystal, Andrew D. ·From the Insomnia and Sleep Research Program, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina. ·J Clin Psychiatry · Pubmed #26335094.

ABSTRACT: Research into the sleep-wake cycle has provided new treatment targets for patients with insomnia as well as a better understanding of how medications affect sleep processes. Current insomnia medications, including benzodiazepines and nonbenzodiazepines, focus on enhancing sleep-promoting systems through broad antagonism of GABA. Other medications that promote sleep by blocking wake-promoting systems include antidepressants, antipsychotics, and antihistamines, but adverse effects and nonspecific therapeutic effects limit their use. New and emerging insomnia medications are focusing on blocking wake-promoting systems via more selective antagonism of orexin, serotonin, and norepinephrine. These medications may offer improved efficacy with fewer adverse effects.

7 Review Insomnia in HIV-infected patients: pathophysiologic implications. 2014

Low, Yinghui / Goforth, Harold / Preud'homme, Xavier / Edinger, Jack / Krystal, Andrew. ·Insomnia and Sleep Research Program, Department of Psychiatry, Duke University School of Medicine, Durham, NC, USA. ·AIDS Rev · Pubmed #24522778.

ABSTRACT: The prevalence of insomnia in the HIV-seropositive population is estimated to be 29-97%, far greater than the 10% general population prevalence. We carried out a systematic review to assess whether the prevalence of insomnia is indeed higher in HIV-seropositive patients and to better understand the correlates of insomnia in order to attempt to explain the dramatically higher prevalence. Nineteen studies met our search criteria and were included in this review. We found that prior studies estimated the rate of disturbed sleep, but not a single study estimated the prevalence of insomnia using insomnia diagnostic criteria, which require that sleep disturbance occur frequently, persistently, and in association with impairment in quality of life or daytime function. We also found that in addition to correlates of sleep disturbance seen in the general population, there are also correlates specific to the HIV-seropositive population: stage and duration of HIV infection, and cognitive impairment. The most important conclusion of this review is that the prevalence of insomnia which meets diagnostic criteria has yet to be estimated in populations of HIV-seropositive patients and studies are needed to estimate this prevalence rate. The rate of sleep disturbance identified in HIV-infected patients (29-97%) should not be compared against the approximately 10% prevalence of clinically significant insomnia in the general population, which would suggest that HIV infection is associated with an alarming increase in sleep problems. Instead, this rate is best compared with the rate of sleep disturbance in the general population, which is roughly 33%.

8 Review Understanding the sleep-wake cycle: sleep, insomnia, and the orexin system. 2013

Krystal, Andrew D / Benca, Ruth M / Kilduff, Thomas S. · ·J Clin Psychiatry · Pubmed #24107804.

ABSTRACT: -- No abstract --

9 Review Review of the histamine system and the clinical effects of H1 antagonists: basis for a new model for understanding the effects of insomnia medications. 2013

Krystal, Andrew D / Richelson, Elliott / Roth, Thomas. ·Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC 27710, USA. kryst001@mc.duke.edu ·Sleep Med Rev · Pubmed #23357028.

ABSTRACT: The pharmacologic management of insomnia has long been dominated by agents that facilitate gamma amino butyric acid inhibition. These agents have served as the clinical model for understanding the pharmacodynamic effects of insomnia agents according to which sleep effects parallel plasma drug levels (pharmacokinetic effects). Agents with other mechanisms also exist for treating insomnia; however, their effects are less well understood. Many of these diminish the activity in one or more of the key wake-promoting systems. This review focuses on one such mechanism, blockade of the wake promoting effects of histamine via H1 receptor antagonism. Although drugs with H1 antagonist effects have long been available, this review was prompted by new studies of a selective H1 antagonist, which provide the first indication of the effects that are specifically associated with H1 antagonism. The findings do not conform to our long-standing model of insomnia agents in that factors other than drug blood level are needed to explain the clinical effects. We suggest a model for understanding these unique effects based on a review of the basic neurobiology of the histamine system. In addition to drug blood level, clinical effects reflect circadian variation in activity in the histamine system and other parallel wake promoting systems as well as factors such as pain and stress. We hypothesize that significant sleep enhancing effects are likely when the histamine system is relatively active and the activity in other parallel wake promoting systems is relatively minimal. Although the focus of this review is on the novel properties of H1 antagonism, the principles that emerge from this analysis are most likely relevant to all agents that selectively block wake promoting systems, and as such, this review provides a new paradigm for understanding the effects of insomnia medications.

10 Review Pharmacological advances in the treatment of insomnia. 2011

Richey, Sarah M / Krystal, Andrew D. ·Mid-Atlantic Permanente Medical Group, Fairfax, Virginia 22033, USA. sarah.m.richey@kp.org ·Curr Pharm Des · Pubmed #21476952.

ABSTRACT: Insomnia is a highly prevalent condition, and due to ongoing demand from patients suffering with this condition, new pharmacological treatments are actively being sought. As our neurophysiological understanding of insomnia grows, so too do the available treatment options. A significant advance in the treatment of insomnia came with the development of the nonbenzodiazepine hypnotic medications, zolpidem, zaleplon and eszopiclone. These medications have shorter durations of action than many traditional benzodiazepines and may be associated with less risk of tolerance and abuse. They have also been demonstrated to be helpful in cases in which insomnia is comorbid with depression or anxiety, leading to beneficial effects not only with sleep but also with mood and anxiety symptoms. Melatonin, a naturally-occurring substance intimately involved in the regulation of the circadian rhythm, has also been explored as a hypnotic. Little data to date support its use; however, there is evidence that ramelteon, a melatonin agonist, may be helpful for sleep initiation difficulties. Tri-cyclic antidepressants have long been used for insomnia, but use has been limited by unwanted anticholinergic side effects. Low-dose doxepin, at doses of 3 and 6mg, has been demonstrated to have the unique property among its class of being free of anticholinergic effects at those doses. In addition, it seems to have particular efficacy for sleep maintenance insomnia, exhibiting the most robust effects in the latter third of the night. The hypocretin/orexin system has been identified as a possible target. Almorexant, a hypocretin/orexin antagonist displayed evidence of efficacy during Phase III clinical trials but these trials were recently discontinued due to its side effect profile. Another hypocretin/orexin antagonist with a different mechanism of action, MK-4035, is presently in clinical trials. Serotonin antagonists and inverse agonists have been investigated; however, a recent trial with APD125 was discontinued due to lack of efficacy. Sodium oxybate has been used off-label for insomnia by some providers, although data supporting its use are limited. While the sleep-promoting effects of GABA(A) (nonbenzodiazepines and benzodiazepines) enhancement is well-established, newer research examining other mechanisms of action suggest that agents which modulate the histaminergic, serotonergic, melontonergic, and hypocretin/orexin and perhaps GABA-B systems show promise.

11 Review British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. 2010

Wilson, S J / Nutt, D J / Alford, C / Argyropoulos, S V / Baldwin, D S / Bateson, A N / Britton, T C / Crowe, C / Dijk, D-J / Espie, C A / Gringras, P / Hajak, G / Idzikowski, C / Krystal, A D / Nash, J R / Selsick, H / Sharpley, A L / Wade, A G. ·Psychopharmacology Unit, University of Bristol, Bristol, UK. Sue.Wilson@bristol.ac.uk ·J Psychopharmacol · Pubmed #20813762.

ABSTRACT: Sleep disorders are common in the general population and even more so in clinical practice, yet are relatively poorly understood by doctors and other health care practitioners. These British Association for Psychopharmacology guidelines are designed to address this problem by providing an accessible up-to-date and evidence-based outline of the major issues, especially those relating to reliable diagnosis and appropriate treatment. A consensus meeting was held in London in May 2009. Those invited to attend included BAP members, representative clinicians with a strong interest in sleep disorders and recognized experts and advocates in the field, including a representative from mainland Europe and the USA. Presenters were asked to provide a review of the literature and identification of the standard of evidence in their area, with an emphasis on meta-analyses, systematic reviews and randomized controlled trials where available, plus updates on current clinical practice. Each presentation was followed by discussion, aimed to reach consensus where the evidence and/or clinical experience was considered adequate or otherwise to flag the area as a direction for future research. A draft of the proceedings was then circulated to all participants for comment. Key subsequent publications were added by the writer and speakers at draft stage. All comments were incorporated as far as possible in the final document, which represents the views of all participants although the authors take final responsibility for the document.

12 Review The pharmacologic management of insomnia in patients with HIV. 2009

Omonuwa, Toma S / Goforth, Harold W / Preud'homme, Xavier / Krystal, Andrew D. ·Duke University School of Medicine, Durham, NC, USA. ·J Clin Sleep Med · Pubmed #19960648.

ABSTRACT: Insomnia is common in human immunodeficiency virus (HIV) seropositive populations. Some studies have estimated as many as 70% of HIV patients experience insomnia at some point during their illness. Insomnia has been linked to reduced quality of life as well as treatment non-adherence in these patients. However, there has been very limited research on the treatment of insomnia in this setting. Lacking treatment trials, we carried out a review of the available literature relevant to the pharmacologic treatment of insomnia in HIV seropositive individuals in order to provide guidance for the clinical management of this complex population. A systematic MEDLINE search was performed using as search terms each of the FDA approved or commonly prescribed insomnia medications and "insomnia and HIV." In addition, we reviewed the published literature on HIV therapies and common comorbid conditions and their interactions with insomnia therapies. We found 4 primary factors affecting the pharmacotherapy of insomnia in individuals with HIV: (1) medications used to treat HIV; (2) antibiotics used to treat opportunistic infections; (3) the HIV infection itself; and (4) conditions frequently associated with HIV infection. The means by which these factors affect the expected risk-benefit profile of insomnia therapies is discussed, and recommendations are made for choosing medications in patients encountered in clinical practice.

13 Review A compendium of placebo-controlled trials of the risks/benefits of pharmacological treatments for insomnia: the empirical basis for U.S. clinical practice. 2009

Krystal, Andrew D. ·Insomnia and Sleep Research Laboratory, Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Duke South Hospital, Trent Drive, Durham, NC 27710, USA. kryst001@mc.duke.edu ·Sleep Med Rev · Pubmed #19153052.

ABSTRACT: For many years practitioners have had limited data from double-blind, placebo-controlled studies to guide the types of decision-making needed to optimally manage patients with insomnia in clinical practice. However, in recent years there has been a great increase in insomnia research studies that address issues of clinical importance. This body of work represents an increasingly useful empirical basis for making clinical practice decisions. The purpose of this article is to compile the body of work on the pharmacological management of insomnia to make it available in as accessible form as possible for optimal application in clinical practice with the hopes that doing so will decrease the gap separating the available research and the clinical management of insomnia and, thereby, improve the care of the many individuals who suffer from this condition. The review of studies consists of the following sections: 1) basic pharmacology; 2) double-blind, placebo-controlled trials in adults with primary insomnia; 3) double-blind, placebo-controlled trials in elderly patients with primary insomnia; 4) adverse effects reported in placebo-controlled trials in elderly primary insomnia patients; 5) double-blind, placebo-controlled trials in adults and the elderly as a function of treatment duration; 6) double-blind, placebo-controlled trials of the treatment of comorbid insomnia. Issues related to the application of these data to clinical practice are discussed in the text.

14 Clinical Trial Suvorexant in Elderly Patients with Insomnia: Pooled Analyses of Data from Phase III Randomized Controlled Clinical Trials. 2017

Herring, W Joseph / Connor, Kathryn M / Snyder, Ellen / Snavely, Duane B / Zhang, Ying / Hutzelmann, Jill / Matzura-Wolfe, Deborah / Benca, Ruth M / Krystal, Andrew D / Walsh, James K / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck & Co., Inc., Kenilworth, NJ. Electronic address: william.herring@merck.com. · Merck & Co., Inc., Kenilworth, NJ. · Department of Psychiatry and Human Behavior, School of Medicine, University of California-Irvine, Irvine, CA. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC. · Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, MO. · Henry Ford Hospital Sleep Center, Detroit, MI. ·Am J Geriatr Psychiatry · Pubmed #28427826.

ABSTRACT: OBJECTIVE: Suvorexant is an orexin receptor antagonist approved for treating insomnia at doses of 10-20 mg. Previously reported phase III results showed that suvorexant was effective and well-tolerated in a combined-age population (elderly and nonelderly adults). The present analysis evaluated the clinical profile of suvorexant specifically in the elderly. METHODS: Prespecified subgroup analyses of pooled 3-month data from two (efficacy) and three (safety) randomized, double-blind, placebo-controlled, parallel-group trials. In each trial, elderly (≥65 years) patients with insomnia were randomized to suvorexant 30 mg, suvorexant 15 mg, and placebo. By design, fewer patients were randomized to 15 mg. Patient-reported and polysomnographic (subset of patients) sleep maintenance and onset endpoints were measured. RESULTS: Suvorexant 30 mg (N = 319) was effective compared with placebo (N = 318) on patient-reported and polysomnographic sleep maintenance, and onset endpoints at Night 1 (polysomnographic endpoints)/Week 1 (patient-reported endpoints), Month 1, and Month 3. Suvorexant 15 mg (N = 202 treated) was also effective across these measures, although the onset effect was less evident at later time points. The percentages of patients discontinuing because of adverse events over 3 months were 6.4% for 30 mg (N = 627 treated), 3.5% for 15 mg (N = 202 treated), and 5.5% for placebo (N = 469 treated). Somnolence was the most common adverse event (8.8% for 30 mg, 5.4% for 15 mg, 3.2% for placebo). CONCLUSION: Suvorexant generally improved sleep maintenance and onset over 3 months of nightly treatment and was well-tolerated in elderly patients with insomnia (clinicaltrials.gov; NCT01097616, NCT01097629, NCT01021813).

15 Clinical Trial Clinical profile of suvorexant for the treatment of insomnia over 3 months in women and men: subgroup analysis of pooled phase-3 data. 2017

Herring, W Joseph / Connor, Kathryn M / Snyder, Ellen / Snavely, Duane B / Zhang, Ying / Hutzelmann, Jill / Matzura-Wolfe, Deborah / Benca, Ruth M / Krystal, Andrew D / Walsh, James K / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck & Co., Inc., Kenilworth, NJ, USA. william_herring@merck.com. · Merck & Co., Inc., UG 4C-13, PO Box 1000, North Wales, PA, 19454-1099, USA. william_herring@merck.com. · Merck & Co., Inc., Kenilworth, NJ, USA. · Department of Psychiatry and Human Behavior, University of California-Irvine, Irvine, CA, USA. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA. · Sleep Medicine and Research Center, St., Luke's Hospital, St. Louis, MO, USA. · Henry Ford Hospital Sleep Center, Detroit, MI, USA. ·Psychopharmacology (Berl) · Pubmed #28265715.

ABSTRACT: RATIONALE: Sex-related differences in the clinical profiles of some insomnia medications have been previously reported. OBJECTIVE: To evaluate the clinical profile of suvorexant, a novel orexin receptor antagonist approved for treating insomnia at doses up to 20 mg, by sex subgroups. METHODS: Efficacy analyses by sex were based on pooled data from two similar phase 3, randomized, double-blind, placebo-controlled, 3-month trials in elderly (≥65 years) and non-elderly (18-64 years) insomnia patients. Two age-adjusted (non-elderly/elderly) dose regimes of 40/30 and 20/15 mg were evaluated, with fewer patients assigned to 20/15 mg. Efficacy was assessed by patient-reported outcomes (N = 1264 women, 707 men) and by polysomnography endpoints in ~75% of patients. Safety analyses by sex (N = 1744 women, 1065 men) included pooled data from the two 3-month trials plus 3-month data from a safety trial of 40/30 mg. RESULTS: The sex subgroup efficacy analyses mirrored the improvements seen for suvorexant 40/30 and 20/15 mg over placebo on patient-reported outcomes and polysomnography sleep maintenance and onset endpoints in the primary analyses; 95% CIs excluded zero in favor of suvorexant for most endpoints in both sexes, and similar efficacy was observed between sexes (95% CIs overlapped). Suvorexant was well-tolerated in women and men, although women in all treatment groups (including placebo) reported more adverse events than men. The most frequent adverse event was somnolence (women: 11.1% for 40/30 mg, 8.5% for 20/15 mg, 2.3% for placebo; men: 10.1% for 40/30 mg, 3.4% for 20/15 mg, 4.2% for placebo). CONCLUSION: Suvorexant was generally effective and well-tolerated in both women and men with insomnia. ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629, NCT01021813.

16 Clinical Trial Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials. 2016

Herring, W Joseph / Connor, Kathleen M / Snyder, Ellen / Snavely, Duane B / Zhang, Ying / Hutzelmann, Jill / Matzura-Wolfe, Deborah / Benca, Ruth M / Krystal, Andrew D / Walsh, James K / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck & Co., Inc., Kenilworth, NJ. · University of Wisconsin, Madison, WI. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC. · Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, MO. · Henry Ford Hospital Sleep Center, Detroit, MI. ·J Clin Sleep Med · Pubmed #27397664.

ABSTRACT: STUDY OBJECTIVES: Suvorexant is an orexin receptor antagonist approved for treating insomnia at a maximum dose of 20 mg. Phase-3 trials evaluated two age-adjusted (non-elderly/elderly) dose-regimes of 40/30 mg and 20/15 mg with the primary focus on 40/30 mg. We report here results from pooled analyses of the 20/15 mg dose-regime, which was evaluated as a secondary objective in the trials. METHODS: Prespecified analysis of pooled data from two identical randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in non-elderly (18-64 years) and elderly (≥ 65 years) patients with insomnia. Patients were randomized to suvorexant 20/15 mg (non-elderly/elderly), suvorexant 40/30 mg (non-elderly/elderly), or placebo; by design, fewer patients were randomized to 20/15 mg. Efficacy was assessed by self-reported and polysomnography (PSG; subset of patients) sleep maintenance and onset endpoints. RESULTS: Suvorexant 20/15 mg (N = 493 treated) was effective compared to placebo (N = 767 treated) on patient-reported and PSG sleep maintenance and onset endpoints at Night-1 (PSG endpoints) / Week-1 (subjective endpoints), Month-1 and Month-3, except for effects on PSG sleep onset at Month-3. Suvorexant 20/15 mg was generally well tolerated, with 3% of patients discontinuing due to adverse events over 3 months vs. 5.2% on placebo. Somnolence was the most common adverse event (6.7% vs. 3.3% for placebo). There was no systematic evidence of rebound or withdrawal signs or symptoms when suvorexant was discontinued after 3 months of nightly use. CONCLUSIONS: Suvorexant 20/15 mg improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov trial registration numbers: NCT01097616, NCT01097629.

17 Clinical Trial Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials. 2016

Herring, W Joseph / Connor, Kathryn M / Ivgy-May, Neely / Snyder, Ellen / Liu, Ken / Snavely, Duane B / Krystal, Andrew D / Walsh, James K / Benca, Ruth M / Rosenberg, Russell / Sangal, R Bart / Budd, Kerry / Hutzelmann, Jill / Leibensperger, Heather / Froman, Samar / Lines, Christopher / Roth, Thomas / Michelson, David. ·Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey. Electronic address: william_herring@merck.com. · Merck Sharp & Dohme Corporation, Whitehouse Station, New Jersey. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina. · Sleep Medicine and Research Center, St. Luke's Hospital, St. Louis, Missouri. · University of Wisconsin, Madison, Wisconsin. · Atlanta Sleep Medicine Clinic, Atlanta, Georgia. · Sleep Disorders Institute & Attention Disorders Institute, Oakland University William Beaumont School of Medicine, Sterling Heights. · Henry Ford Hospital Sleep Center, Detroit, Michigan. ·Biol Psychiatry · Pubmed #25526970.

ABSTRACT: BACKGROUND: Suvorexant is an orexin receptor antagonist for treatment of insomnia. We report results from two pivotal phase 3 trials. METHODS: Two randomized, double-blind, placebo-controlled, parallel-group, 3-month trials in nonelderly (18-64 years) and elderly (≥65 years) patients with insomnia. Suvorexant doses of 40/30 mg (nonelderly/elderly) and 20/15 mg (nonelderly/elderly) were evaluated. The primary focus was 40/30 mg, with fewer patients randomized to 20/15 mg. There was an optional 3-month double-blind extension in trial 1. Each trial included a 1-week, randomized, double-blind run-out after double-blind treatment to assess withdrawal/rebound. Efficacy was assessed at week 1, month 1, and month 3 by patient-reported subjective total sleep time and time to sleep onset and in a subset of patients at night 1, month 1, and month 3 by polysomnography end points of wakefulness after persistent sleep onset and latency to onset of persistent sleep (LPS). One thousand twenty-one patients were randomized in trial 1 and 1019 patients in trial 2. RESULTS: Suvorexant 40/30 mg was superior to placebo on all subjective and polysomnography end points at night 1/week 1, month 1, and month 3 in both trials, except for LPS at month 3 in trial 2. Suvorexant 20/15 mg was superior to placebo on subjective total sleep time and wakefulness after persistent sleep onset at night 1/week 1, month 1, and month 3 in both trials and at most individual time points for subjective time to sleep onset and LPS in each trial. Both doses of suvorexant were generally well tolerated, with <5% of patients discontinuing due to adverse events over 3 months. The results did not suggest the emergence of marked rebound or withdrawal signs or symptoms when suvorexant was discontinued. CONCLUSIONS: Suvorexant improved sleep onset and maintenance over 3 months of nightly treatment and was generally safe and well tolerated.

18 Clinical Trial Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. 2014

Michelson, David / Snyder, Ellen / Paradis, Erin / Chengan-Liu, Mary / Snavely, Duane B / Hutzelmann, Jill / Walsh, James K / Krystal, Andrew D / Benca, Ruth M / Cohn, Martin / Lines, Christopher / Roth, Thomas / Herring, W Joseph. ·Merck & Co Inc, Whitehouse Station, NJ, USA. Electronic address: david_michelson@merck.com. · Merck & Co Inc, Whitehouse Station, NJ, USA. · Sleep Medicine and Research Center, St Luke's Hospital, St Louis, MO, USA. · Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA. · University of Wisconsin, Madison, WI, USA. · Omnitrials, Naples, FL, USA. · Henry Ford Hospital Sleep Center, Detroit, MI, USA. ·Lancet Neurol · Pubmed #24680372.

ABSTRACT: BACKGROUND: Suvorexant (MK-4305) is an orexin receptor antagonist shown to be efficacious for insomnia over 3 months. We aimed to assess its clinical profile during and after 1 year of treatment. METHODS: We did a randomised, placebo-controlled, parallel-group trial at 106 investigational centres in the Americas, Australia, Europe, and South Africa from December, 2009, to August, 2011. Patients aged 18 years or older with primary insomnia by DSM-IV-TR criteria were assigned using a computer-generated randomised allocation schedule to receive nightly suvorexant (40 mg for patients younger than 65 years, 30 mg for patients aged 65 years or older) or placebo at a 2:1 ratio for 1 year with a subsequent 2-month randomised discontinuation phase in which patients on suvorexant either continued suvorexant or were abruptly switched to placebo while patients on placebo remained on placebo. Treatment assignment was masked from patients and investigators. The primary objective was to assess the safety and tolerability of suvorexant for up to 1 year. Secondary objectives were to assess the efficacy of suvorexant for improving patient-reported subjective total sleep time (sTST) and time to sleep onset (sTSO) over the first month of treatment. Efficacy endpoints over the first month were assessed with a mixed model with terms for baseline value of the response variable, age, sex, region, treatment, time, and treatment by time interaction. This trial is registered with ClinicalTrials.gov, number NCT01021813. FINDINGS: 322 (62%) of 522 patients randomly assigned to receive suvorexant and 162 (63%) of 259 assigned to receive placebo completed the 1-year phase. Over 1 year, 362 (69%) of 521 patients treated with suvorexant experienced any adverse events compared with 164 (64%) of 258 treated with placebo. Serious adverse events were recorded in 27 patients (5%) who received suvorexant and 17 (7%) who received placebo. The most common adverse event, somnolence, was reported for 69 patients (13%) who received suvorexant and seven (3%) who received placebo. At month 1, suvorexant (517 patients in the efficacy population) showed greater efficacy than placebo (254 in the efficacy population) in improving sTST (38·7 min vs 16·0 min; difference 22·7, 95% CI 16·4 to 29·0; p<0·0001) and sTSO (-18·0 min vs -8·4 min, difference -9·5, -14·6 to -4·5; p=0·0002). INTERPRETATION: Our findings show that suvorexant was generally safe and well tolerated over 1 year of nightly treatment in patients with insomnia, with efficacy noted for subjective measures of sleep onset and maintenance. FUNDING: Merck & Co Inc.

19 Clinical Trial A 12-week, randomized, double-blind, placebo-controlled study evaluating the effect of eszopiclone 2 mg on sleep/wake function in older adults with primary and comorbid insomnia. 2010

Ancoli-Israel, Sonia / Krystal, Andrew D / McCall, W Vaughn / Schaefer, Kendyl / Wilson, Amy / Claus, Raymond / Rubens, Robert / Roth, Thomas. ·Department of Psychiatry, University of California San Diego, San Diego, CA 92093-0733, USA. sancoliisrael@ucsd.edu ·Sleep · Pubmed #20175406.

ABSTRACT: BACKGROUND: Longer-term pharmacologic studies for insomnia in older individuals are sparse. OBJECTIVE: To evaluate the efficacy and safety of 12 weeks of nightly eszopiclone in elderly outpatients with insomnia. METHODS: Participants (65-85 years) met DSM-IV-TR criteria for insomnia with total sleep times (TST) < or = 6 h, and wake time after sleep onset (WASO) > or = 45 min. Participants were randomized to 12 weeks of eszopiclone 2 mg (n = 194) or placebo (n = 194), followed by a 2-week single-blind placebo run-out. Subject-reported measures of sleep (sTST, sleep latency [sSL], sWASO) and daytime function (alertness, concentration, wellbeing, ability to function) were assessed. AEs were monitored. RESULTS: Subjects treated with 2 mg eszopiclone slept longer at night on average and at every individual time point compared to baseline than placebo subjects, as measured by TST over the 12-week double-blind period (P < 0.0001). Mean sTST over the double-blind period for eszopiclone-treated subjects was 360.08 min compared to 297.86 min at baseline, a mean change of 63.24 min. Over the double-blind period, eszopiclone-treated subjects also experienced a significantly greater improvement in sSL compared to placebo, with a mean decrease of 24.62 min versus a mean decrease of 19.92 min, respectively (P = 0.0014). Eszopiclone subjects also experienced a significantly greater decrease in WASO (mean decrease of 36.4 min) compared to placebo subjects (decrease of 14.8 min) (P < 0.0001). Post-discontinuation, sleep parameters were statistically improved versus baseline for eszopiclone (P-values < or = 0.01), indicating no rebound. The most common AEs (> or = 5%) were headache (eszopiclone 13.9%, placebo 12.4%), unpleasant taste (12.4%, 1.5%), and nasopharyngitis (5.7%, 6.2%). CONCLUSION: In this Phase IV trial of older adults with insomnia, eszopiclone significantly improved patient-reported sleep and daytime function relative to placebo. Improvements occurred within the first week and were maintained for 3 months, with no evidence of rebound insomnia following discontinuation. The 12 weeks of treatment were well tolerated. CLINICAL TRIAL INFORMATION: A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia; Registration #NCT00386334; URL - http://www.clinicaltrials.gov/ct2/show/NCT00386334?term=eszopiclone&rank=24

20 Article Treating insomnia in depression: Insomnia related factors predict long-term depression trajectories. 2018

Bei, Bei / Asarnow, Lauren D / Krystal, Andrew / Edinger, Jack D / Buysse, Daniel J / Manber, Rachel. ·Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University. · Department of Psychiatry and Behavioral Sciences, Stanford University. · School of Medicine, University of California, San Francisco. · Department of Medicine, National Jewish Health. · Department of Psychiatry, University of Pittsburgh. ·J Consult Clin Psychol · Pubmed #29504795.

ABSTRACT: OBJECTIVE: Insomnia and major depressive disorders (MDD) often co-occur, and such comorbidity has been associated with poorer outcomes for both conditions. However, individual differences in depressive symptom trajectories during and after treatment are poorly understood in comorbid insomnia and depression. This study explored the heterogeneity in long-term depression change trajectories, and examined their correlates, particularly insomnia-related characteristics. METHOD: Participants were 148 adults (age M ± SD = 46.6 ± 12.6, 73.0% female) with insomnia and MDD who received antidepressant pharmacotherapy, and were randomized to 7-session Cognitive Behavioral Therapy for Insomnia or control conditions over 16 weeks with 2-year follow-ups. Depression and insomnia severity were assessed at baseline, biweekly during treatment, and every 4 months thereafter. Sleep effort and beliefs about sleep were also assessed. RESULTS: Growth mixture modeling revealed three trajectories: (a) Partial-Responders (68.9%) had moderate symptom reduction during early treatment (p value < .001) and maintained mild depression during follow-ups. (b) Initial-Responders (17.6%) had marked symptom reduction during treatment (p values < .001) and low depression severity at posttreatment, but increased severity over follow-up (p value < .001). (c) Optimal-Responders (13.5%) achieved most gains during early treatment (p value < .001), continued to improve (p value < .01) and maintained minimal depression during follow-ups. The classes did not differ significantly on baseline measures or treatment received, but differed on insomnia-related measures after treatment began (p values < .05): Optimal-Responders consistently endorsed the lowest insomnia severity, sleep effort, and unhelpful beliefs about sleep. CONCLUSIONS: Three depression symptom trajectories were observed among patients with comorbid insomnia and MDD. These trajectories were associated with insomnia-related constructs after commencing treatment. Early changes in insomnia characteristics may predict long-term depression outcomes. (PsycINFO Database Record

21 Article Pilot prospective study of post-surgery sleep and EEG predictors of post-operative delirium. 2017

Evans, Joanna L / Nadler, Jacob W / Preud'homme, Xavier A / Fang, Eric / Daughtry, Rommie L / Chapman, Joseph B / Attarian, David / Wellman, Samuel / Krystal, Andrew D. ·Duke University School of Medicine, Durham, NC, USA. · University of Rochester Medical Center, Rochester, NY, USA. · Duke-NUS Graduate Medical School, Singapore. · Duke University School of Medicine, Durham, NC, USA; University of California San Francisco, San Francisco, CA, USA. Electronic address: andrew.krystal@ucsf.edu. ·Clin Neurophysiol · Pubmed #28618293.

ABSTRACT: OBJECTIVE: Delirium is a common post-operative complication associated with significant costs, morbidity, and mortality. We sought sleep/EEG predictors of delirium present prior to delirium symptoms to facilitate developing and targeting therapies. METHODS: Continuous EEG data were obtained in 12 patients post-orthopedic surgery from the day of surgery until delirium assessment on post-operative day 2 (POD2). RESULTS: Diminished total sleep time (r=-0.68; p<0.05) and longer latency to sleep onset (r=0.67; p<0.05) on the first night in the hospital were associated with greater POD2 delirium severity. Patients experiencing delirium slept 2.4h less and took 2h longer to fall asleep. Greater waking EEG delta power (r=0.84; p<0.05) on POD1 and less non-REM sleep EEG delta power (r=-0.72; p<0.05) on night 2 also predicted POD2 delirium severity. CONCLUSIONS: Loss of sleep on night1 post-surgery is an early predictor of subsequent delirium. EEG Delta Power alterations in waking and sleep appear to be later indicators of impending delirium. Further work is needed to evaluate reproducibility/generalizability and assess whether sleep loss contributes to causing delirium. SIGNIFICANCE: This first study to prospectively collect continuous EEG data for an extended period prior to delirium onset identified EEG-derived indices that predict subsequent delirium that could aid in developing and targeting therapies.

22 Article Insomnia Patients With Objective Short Sleep Duration Have a Blunted Response to Cognitive Behavioral Therapy for Insomnia. 2017

Bathgate, Christina J / Edinger, Jack D / Krystal, Andrew D. ·Department of Medicine, National Jewish Health, Denver, CO. · Department of Psychiatry, Duke University Medical Center, Durham, NC. ·Sleep · Pubmed #28364452.

ABSTRACT: Study Objectives: This study examined whether individuals with insomnia and objective short sleep duration <6 h, a subgroup with greater risks of adverse health outcomes, differ in their response to cognitive-behavioral therapy for insomnia (CBT-I) when compared to individuals with insomnia and normal sleep duration ≥6 h. Methods: Secondary analyses of a randomized, clinical trial with 60 adult participants (n = 31 women) from a single academic medical center. Outpatient treatment lasted 8 weeks, with a final follow-up conducted at 6 months. Mixed-effects models controlling for age, sex, CBT-I treatment group assignment, and treatment provider examined sleep parameters gathered via actigraphy, sleep diaries, and an Insomnia Symptom Questionnaire (ISQ) across the treatment and follow-up period. Results: Six months post-CBT-I treatment, individuals with insomnia and normal sleep duration ≥6 h fared significantly better on clinical improvement milestones than did those with insomnia and short sleep duration <6 h. Specifically, individuals with insomnia and normal sleep duration had significantly higher insomnia remission (ISQ < 36.5; χ2[1, N = 60] = 44.72, p < .0001), more normative sleep efficiency (SE) on actigraphy (SE > 80%; χ2[1, N = 60] = 21, p < .0001), normal levels of middle of the night wake after sleep onset (MWASO) <31 minutes (χ2[1, N = 60] = 37.85, p < .0001), and a >50% decline in MWASO (χ2[1, N = 60] = 60, p < .0001) compared to individuals with insomnia and short sleep duration. Additionally, those with insomnia and normal sleep duration had more success decreasing their total wake time (TWT) at the 6-month follow-up compared to those with insomnia and short sleep duration (χ2[2, N = 60] = 44.1, p < .0001). Receiver-operating characteristic curve analysis found that using a 6-h cutoff with actigraphy provided a 95.7% sensitivity and 91.9% specificity for determining insomnia remission, with the area under the curve = 0.986. Conclusions: Findings suggest that individuals with insomnia and objective short sleep duration <6 h are significantly less responsive to CBT-I than those with insomnia and normal sleep duration ≥6 h. Using an actigraphy TST cutoff of 6 hours to classify sleep duration groups was highly accurate and provided good discriminant value for determining insomnia remission.

23 Article Cognitive Behavioral Insomnia Therapy for Those With Insomnia and Depression: A Randomized Controlled Clinical Trial. 2017

Carney, Colleen E / Edinger, Jack D / Kuchibhatla, Maragatha / Lachowski, Angela M / Bogouslavsky, Olya / Krystal, Andrew D / Shapiro, Colin M. ·Ryerson University. · National Jewish Health. · Duke University Medical Center. · University of Toronto. ·Sleep · Pubmed #28199710.

ABSTRACT: Study Objective: To compare cognitive behavioral therapy for insomnia (CBT-I) + antidepressant medication (AD) against treatments that target solely depression or solely insomnia. Design: A blinded, randomized split-plot experimental study. Setting: Two urban academic clinical centers. Participants: 107 participants (68% female, mean age 42 ± 11) with major depressive disorder and insomnia. Interventions: Randomization was to one of three groups: antidepressant (AD; escitalopram) + CBT-I (4 sessions), CBT-I + placebo pill, or AD + 4-session sleep hygiene control (SH). Measurements and Results: Subjective sleep was assessed via 2 weeks of daily sleep diaries (use of medication was covaried in all analyses); although there were no statistically significant group differences detected, all groups improved from baseline to posttreatment on subjective sleep efficiency (SE) and total wake time (TWT) and the effect sizes were large. Objective sleep was assessed via overnight polysomnographic monitoring at baseline and posttreatment; analyses revealed both CBT groups improved on TWT (p = .03), but the AD + SH group worsened. There was no statistically significant effect for PSG SE (p = .07). There was a between groups medium effect observed for the AD + SH and CBT + placebo group differences on diary TWT and both PSG variables. All groups improved significantly from baseline to posttreatment on the Hamilton Rating Scale for Depression (HAMD-17); the groups did not differ. Conclusions: Although all groups self-reported sleeping better after treatment, only the CBT-I groups improved on objective sleep, and AD + SH's sleep worsened. This suggests that we should be treating sleep in those with depression with an effective insomnia treatment and relying on self-report obscures sleep worsening effects. All groups improved on depression, even a group with absolutely no depression-focused treatment component (CBT-I + placebo). The depression effect in CBT-I only group has been reported in other studies, suggesting that we should further investigate the antidepressant properties of CBT-I.

24 Article Should Internet Cognitive Behavioral Therapy for Insomnia Be the Primary Treatment Option for Insomnia?: Toward Getting More SHUTi. 2017

Krystal, Andrew D / Prather, Aric A. ·Department of Psychiatry, University of California, San Francisco2Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina. · Department of Psychiatry, University of California, San Francisco. ·JAMA Psychiatry · Pubmed #27902827.

ABSTRACT: -- No abstract --

25 Article Are Patients with Childhood Onset of Insomnia and Depression More Difficult to Treat Than Are Those with Adult Onsets of These Disorders? A Report from the TRIAD Study. 2017

Edinger, Jack D / Manber, Rachel / Buysse, Daniel J / Krystal, Andrew D / Thase, Michael E / Gehrman, Phillip / Fairholme, Christopher P / Luther, James / Wisniewski, Stephen. ·Department of Medicine, National Jewish Health, Denver, CO. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC. · Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA. · Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA. · Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania and the Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA. · Department of Psychology, University of Idaho, Moscow, ID. · Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA. ·J Clin Sleep Med · Pubmed #27784414.

ABSTRACT: STUDY OBJECTIVES: To determine if patients with childhood onsets (CO) of both major depression and insomnia disorder show blunted depression and insomnia treatment responses to concurrent interventions for both disorders compared to those with adult onsets (AO) of both conditions. METHODS: This study was a secondary analysis of data obtained from a multisite randomized clinical trial designed to test the efficacy of combining a psychological/behavior insomnia therapy with antidepressant medication to enhance depression treatment outcomes in patients with comorbid major depression and insomnia. This study included 27 adults with CO of depression and insomnia and 77 adults with AO of both conditions. They underwent a 16-week treatment including: (1) a standardized two-step pharmacotherapy for depression algorithm, consisting of escitalopram, sertraline, and desvenlafaxine in a prescribed sequence; and (2) either cognitive behavioral insomnia therapy (CBT-I) or a quasi-desensitization control (CTRL) therapy. Main outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Insomnia Severity Index (ISI) completed pre-treatment and every 2 weeks thereafter. RESULTS: The AO and CO groups did not differ significantly in regard to their pre-treatment HRSD-17 and ISI scores. Mixed model analyses that adjusted for the number of insomnia treatment sessions attended showed that the AO group achieved significantly lower, subclinical scores on the HRSD-17 and ISI than did the CO group by the time of study exit. Moreover, a significant group by treatment arm interaction suggested that HRSD-17 scores at study exit remained significantly higher in the CO group receiving the CTRL therapy than was the case for the participants in the CO group receiving CBT-I. Greater proportions of the AO group achieved a priori criteria for remission of insomnia (49.3% vs. 29.2%, p = 0.04) and depression (45.5% vs. 29.6%, p = 0.07) than did those in the CO group. CONCLUSIONS: Patients with comorbid depression and insomnia who experienced the first onset of both disorders in childhood are less responsive to the treatments offered herein than are those with adult onsets of these comorbid disorders. Further research is needed to identify therapies that enhance the depression and insomnia treatment responses of those with childhood onsets of these two conditions.

Next