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Sleep Initiation and Maintenance Disorders: HELP
Articles from Palo Alto
Based on 107 articles published since 2008

These are the 107 published articles about Sleep Initiation and Maintenance Disorders that originated from Palo Alto during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial The power of pooled analyses to inform about the effects of CBTI on outcomes beyond sleep. 2019

Manber, Rachel. ·Department of Psychiatry and Behavioral Sciences, Stanford University, USA. ·Sleep Med Rev · Pubmed #30691658.

ABSTRACT: -- No abstract --

2 Editorial A step towards stepped care: delivery of CBT-I with reduced clinician time. 2015

Manber, Rachel / Simpson, Norah S / Bootzin, Richard R. ·Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA 94301-5597, USA. Electronic address: Rmanber@stanford.edu. · Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA 94301-5597, USA. · Department of Psychology, University of Arizona, USA. ·Sleep Med Rev · Pubmed #25454675.

ABSTRACT: -- No abstract --

3 Review Insomnia in Elderly Patients: Recommendations for Pharmacological Management. 2018

Abad, Vivien C / Guilleminault, Christian. ·Division of Sleep Medicine, Department of Psychiatry and Behavioral Sciences, Stanford Outpatient Medical Center, Stanford University, 450 Broadway St. Pavilion C 2nd Floor MC 5704, Redwood City, CA, 94063, USA. · Division of Sleep Medicine, Department of Psychiatry and Behavioral Sciences, Stanford Outpatient Medical Center, Stanford University, 450 Broadway St. Pavilion C 2nd Floor MC 5704, Redwood City, CA, 94063, USA. cguil@stanford.edu. ·Drugs Aging · Pubmed #30058034.

ABSTRACT: Chronic insomnia affects 57% of the elderly in the United States, with impairment of quality of life, function, and health. Chronic insomnia burdens society with billions of dollars in direct and indirect costs of care. The main modalities in the treatment of insomnia in the elderly are psychological/behavioral therapies, pharmacological treatment, or a combination of both. Various specialty societies view psychological/behavioral therapies as the initial treatment intervention. Pharmacotherapy plays an adjunctive role when insomnia symptoms persist or when patients are unable to pursue cognitive behavioral therapies. Current drugs for insomnia fall into different classes: orexin agonists, histamine receptor antagonists, non-benzodiazepine gamma aminobutyric acid receptor agonists, and benzodiazepines. This review focuses on Food and Drug Administration (FDA)-approved drugs for insomnia, including suvorexant, low-dose doxepin, Z-drugs (eszopiclone, zolpidem, zaleplon), benzodiazepines (triazolam, temazepam), and ramelteon. We review the indications, dosing, efficacy, benefits, and harms of these drugs in the elderly, and discuss data on drugs that are commonly used off-label to treat insomnia, and those that are in clinical development. The choice of a hypnotic agent in the elderly is symptom-based. Ramelteon or short-acting Z-drugs can treat sleep-onset insomnia. Suvorexant or low-dose doxepin can improve sleep maintenance. Eszopiclone or zolpidem extended release can be utilized for both sleep onset and sleep maintenance. Low-dose zolpidem sublingual tablets or zaleplon can alleviate middle-of-the-night awakenings. Benzodiazepines should not be used routinely. Trazodone, a commonly used off-label drug for insomnia, improves sleep quality and sleep continuity but carries significant risks. Tiagabine, sometimes used off-label for insomnia, is not effective and should not be utilized. Non-FDA-approved hypnotic agents that are commonly used include melatonin, diphenhydramine, tryptophan, and valerian, despite limited data on benefits and harms. Melatonin slightly improves sleep onset and sleep duration, but product quality and efficacy may vary. Tryptophan decreases sleep onset in adults, but data in the elderly are not available. Valerian is relatively safe but has equivocal benefits on sleep quality. Phase II studies of dual orexin receptor antagonists (almorexant, lemborexant, and filorexant) have shown some improvement in sleep maintenance and sleep continuity. Piromelatine may improve sleep maintenance. Histamine receptor inverse agonists (APD-125, eplivanserin, and LY2624803) improve slow-wave sleep but, for various reasons, the drug companies withdrew their products.

4 Review Management of side effects during and post-treatment in breast cancer survivors. 2018

Palesh, Oxana / Scheiber, Caroline / Kesler, Shelli / Mustian, Karen / Koopman, Cheryl / Schapira, Lidia. ·Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. · MD Anderson Cancer Center, Houston, TX, USA. · Department of Surgery, University of Rochester, Rochester, NY, USA. · Stanford Cancer Institute, Stanford, CA, USA. ·Breast J · Pubmed #28845551.

ABSTRACT: Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are commonly experienced symptoms that share psychological and physical manifestations. One or more of these symptoms will affect nearly all patients at some point during their course of treatment or survivorship. These side effects are burdensome and reduce patients' quality of life well beyond their cancer diagnosis and associated care treatments. Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are likely to have multiple etiologies that make it difficult to identify the most effective method to manage them. In this review, we summarized the information on cancer-related fatigue, insomnia, and cancer-related cognitive impairment incidence and prevalence among breast cancer patients and survivors as well as recent research findings on pharmaceutical, psychological, and exercise interventions that have shown effectiveness in the treatment of these side effects. Our review revealed that most current pharmaceutical interventions tend to ameliorate symptoms only temporarily without addressing the underlying causes. Exercise and behavioral interventions are consistently more effective at managing chronic symptoms and possibly address an underlying etiology. Future research is needed to investigate effective interventions that can be delivered directly in clinic to a large portion of patients and survivors.

5 Review Hypnosis in Cancer Care. 2017

Wortzel, Joshua / Spiegel, David. ·a Stanford University School of Medicine , Stanford , California , USA. ·Am J Clin Hypn · Pubmed #28557681.

ABSTRACT: Cancer affects a growing proportion of the population as survival improves. The illness and its treatment brings a substantial burden of symptoms, including pain, anxiety, insomnia, and grief. Here, the uses of hypnosis in the treatment of these cancer-related problems will be reviewed. The utility of measuring hypnotizability in the clinical setting will be discussed. The current neurobiology of hypnotizability and hypnosis will be reviewed. Methods and results of using hypnosis for pain control in acute and chronic settings will be presented. Effects of hypnotic analgesia in specific brain regions associated with pain reduction, notably the dorsal anterior cingulate cortex and the somatosensory cortex, underlies its utility as a potent and side-effect free analgesic. Methods for helping those with cancer to better manage their anxiety, insomnia, and grief will be described. These involve facing disease-related stressors while dissociating the experience from somatic arousal. Given the serious complications of medications widely used to treat pain, anxiety, and insomnia, this article provides methods and an evidence base for wider use of techniques involving hypnosis in cancer care. Altering patients' perception of pain, disease-related stress, and anxiety can help change the reality of their life with cancer.

6 Review Cannabis, Cannabinoids, and Sleep: a Review of the Literature. 2017

Babson, Kimberly A / Sottile, James / Morabito, Danielle. ·National Center for PTSD-Dissemination & Training Division, VA Palo Alto Health Care System, 795 Willow Road, Menlo Park, CA, 94025, USA. Kimberly.Babson@va.gov. · Palo Alto University, Palo Alto, CA, USA. · National Center for PTSD-Dissemination & Training Division, VA Palo Alto Health Care System, 795 Willow Road, Menlo Park, CA, 94025, USA. ·Curr Psychiatry Rep · Pubmed #28349316.

ABSTRACT: PURPOSE OF REVIEW: The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication. RECENT FINDINGS: Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term. Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas. CBD may hold promise for REM sleep behavior disorder and excessive daytime sleepiness, while nabilone may reduce nightmares associated with PTSD and may improve sleep among patients with chronic pain. Research on cannabis and sleep is in its infancy and has yielded mixed results. Additional controlled and longitudinal research is critical to advance our understanding of research and clinical implications.

7 Review Beyond the mean: A systematic review on the correlates of daily intraindividual variability of sleep/wake patterns. 2016

Bei, Bei / Wiley, Joshua F / Trinder, John / Manber, Rachel. ·Monash Institute of Cognitive and Clinical Neurosciences, Monash School of Psychological Sciences, Faculty of Biomedical and Psychological Sciences, Monash University, Australia; Centre for Women's Mental Health, Royal Women's Hospital, Australia. Electronic address: bei.bei@monash.edu. · Centre for Primary Care and Prevention, Mary MacKillop Institute for Health Research, Australian Catholic University, Australia. · Melbourne School of Psychological Sciences, University of Melbourne, Australia. · Stanford University School of Medicine, Department of Psychiatry and Behavioral Science, USA. ·Sleep Med Rev · Pubmed #26588182.

ABSTRACT: Features of an individual's sleep/wake patterns across multiple days are governed by two dimensions, the mean and the intraindividual variability (IIV). The existing literature focuses on the means, while the nature and correlates of sleep/wake IIV are not well understood. A systematic search of records in five major databases from inception to November 2014 identified 53 peer-reviewed empirical publications that examined correlates of sleep/wake IIV in adults. Overall, this literature appeared unsystematic and post hoc, with under-developed theoretical frameworks and inconsistent methodologies. Correlates most consistently associated with greater IIV in one or more aspects of sleep/wake patterns were: younger age, non-White race/ethnicity, living alone, physical health conditions, higher body mass index, weight gain, bipolar and unipolar depression symptomatology, stress, and evening chronotype; symptoms of insomnia and poor sleep were associated with higher sleep/wake IIV, which was reduced following sleep interventions. The effects of experimentally reduced sleep/wake IIV on daytime functioning were inconclusive. In extending current understanding of sleep/wake patterns beyond the mean values, IIV should be incorporated as an additional dimension when sleep is examined across multiple days. Theoretical and methodological shortcomings in the existing literature, and opportunities for future research are discussed.

8 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.

9 Review Sleep disturbances as an evidence-based suicide risk factor. 2015

Bernert, Rebecca A / Kim, Joanne S / Iwata, Naomi G / Perlis, Michael L. ·Suicide Prevention Research Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA, USA, rbernert@stanford.edu. ·Curr Psychiatry Rep · Pubmed #25698339.

ABSTRACT: Increasing research indicates that sleep disturbances may confer increased risk for suicidal behaviors, including suicidal ideation, suicide attempts, and death by suicide. Despite increased investigation, a number of methodological problems present important limitations to the validity and generalizability of findings in this area, which warrant additional focus. To evaluate and delineate sleep disturbances as an evidence-based suicide risk factor, a systematic review of the extant literature was conducted with methodological considerations as a central focus. The following methodologic criteria were required for inclusion: the report (1) evaluated an index of sleep disturbance; (2) examined an outcome measure for suicidal behavior; (3) adjusted for presence of a depression diagnosis or depression severity, as a covariate; and (4) represented an original investigation as opposed to a chart review. Reports meeting inclusion criteria were further classified and reviewed according to: study design and timeframe; sample type and size; sleep disturbance, suicide risk, and depression covariate assessment measure(s); and presence of positive versus negative findings. Based on keyword search, the following search engines were used: PubMed and PsycINFO. Search criteria generated N = 82 articles representing original investigations focused on sleep disturbances and suicide outcomes. Of these, N = 18 met inclusion criteria for review based on systematic analysis. Of the reports identified, N = 18 evaluated insomnia or poor sleep quality symptoms, whereas N = 8 assessed nightmares in association with suicide risk. Despite considerable differences in study designs, samples, and assessment techniques, the comparison of such reports indicates preliminary, converging evidence for sleep disturbances as an empirical risk factor for suicidal behaviors, while highlighting important, future directions for increased investigation.

10 Review Pharmacological treatment of sleep disorders and its relationship with neuroplasticity. 2015

Abad, Vivien C / Guilleminault, Christian. ·Psychiatry and Behavioral Science-Division of Sleep Medicine, Stanford University School of Medicine, Palo Alto, CA, USA. ·Curr Top Behav Neurosci · Pubmed #25585962.

ABSTRACT: Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.

11 Review An evidence-based review of insomnia treatment in early recovery. 2014

Kaplan, Katherine A / McQuaid, John / Primich, Charles / Rosenlicht, Nicholas. ·From the Department of Psychiatry (KAK), Stanford University School of Medicine, Stanford, CA · Department of Psychiatry (JM, NR), University of California, San Francisco · and San Francisco VA Medical Center (JM, CP, NR), San Francisco, CA. ·J Addict Med · Pubmed #25369938.

ABSTRACT: Accruing evidence indicates that insomnia is prevalent and persistent in early recovery from substance use disorders and may predict relapse. As such, insomnia treatment after abstinence represents an important area for intervention. This article reviews the literature on insomnia predicting new-onset alcohol and substance use disorders, along with evidence for insomnia predicting relapse in recovering populations. Pharmacological and psychological treatment options are presented, and cognitive-behavioral therapy for insomnia applied to recovering populations is described in detail.

12 Review Sleep disruption in hematopoietic cell transplantation recipients: prevalence, severity, and clinical management. 2014

Jim, Heather S L / Evans, Bryan / Jeong, Jiyeon M / Gonzalez, Brian D / Johnston, Laura / Nelson, Ashley M / Kesler, Shelli / Phillips, Kristin M / Barata, Anna / Pidala, Joseph / Palesh, Oxana. ·Moffitt Cancer Center, Tampa, Florida. Electronic address: heather.jim@moffitt.org. · Department of Psychology, University of South Florida, Tampa, Florida. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California. · Moffitt Cancer Center, Tampa, Florida. · Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, California. · Moffitt Cancer Center, Tampa, Florida; Psychiatry and Legal Medicine PhD Program, Universitat Autònoma de Barcelona, Barcelona, Spain. · Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida. ·Biol Blood Marrow Transplant · Pubmed #24747335.

ABSTRACT: Sleep disruption is common among hematopoietic cell transplant (HCT) recipients, with over 50% of recipients experiencing sleep disruption pre-transplant, with up to 82% of patients experiencing moderate to severe sleep disruption during hospitalization for transplant and up to 43% after transplant. These rates of sleep disruption are substantially higher than what we see in the general population. Although sleep disruption can be distressing to patients and contribute to diminished quality of life, it is rarely discussed during clinical visits. The goal of the current review is to draw attention to sleep disruption and disorders (ie, insomnia, obstructive sleep apnea, restless legs syndrome) as a clinical problem in HCT in order to facilitate patient education, intervention, and research. We identified 35 observational studies published in the past decade that examined sleep disruption or disorders in HCT. Most studies utilized a single item measure of sleep, had small sample size, and included heterogeneous samples of patients. Six studies of the effects of psychosocial and exercise interventions on sleep in HCT have reported no significant improvements. These results highlight the need for rigorous observational and interventional studies of sleep disruption and disorders in HCT recipients..

13 Review The evidence base of sleep restriction therapy for treating insomnia disorder. 2014

Miller, Christopher B / Espie, Colin A / Epstein, Dana R / Friedman, Leah / Morin, Charles M / Pigeon, Wilfred R / Spielman, Arthur J / Kyle, Simon D. ·Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, Australia; Institute of Neuroscience & Psychology, University of Glasgow, UK. Electronic address: chris.miller@sydney.edu.au. · Nuffield Department of Clinical Neurosciences and Sleep & Circadian Neuroscience Institute, University of Oxford, UK. · Phoenix Veterans Affairs Health Care System, USA; Arizona State University College of Nursing and Health Innovation, USA. · Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA. · Université Laval, Québec City, Québec, Canada. · Sleep & Neurophysiology Research Lab, University of Rochester Medical Center, USA; Center of Excellence for Suicide Prevention, U.S. Department of Veterans Affairs, USA. · Cognitive Neuroscience Doctoral Program, The City College of the City University of New York, USA; Weill Cornell Medical College, Center for Sleep Medicine, NY, USA. · School of Psychological Sciences, University of Manchester, UK. ·Sleep Med Rev · Pubmed #24629826.

ABSTRACT: Sleep restriction therapy is routinely used within cognitive behavioral therapy to treat chronic insomnia. However, the efficacy for sleep restriction therapy as a standalone intervention has yet to be comprehensively reviewed. This review evaluates the evidence for the use of sleep restriction therapy in the treatment of chronic insomnia. The literature was searched using web-based databases, finding 1344 studies. Twenty-one were accessed in full (1323 were deemed irrelevant to this review). Nine were considered relevant and evaluated in relation to study design using a standardized study checklist and levels of evidence. Four trials met adequate methodological strength to examine the efficacy of therapy for chronic insomnia. Weighted effect sizes for self-reported sleep diary measures of sleep onset latency, wake time after sleep onset, and sleep efficiency were moderate-to-large after therapy. Total sleep time indicated a small improvement. Standalone sleep restriction therapy is efficacious for the treatment of chronic insomnia for sleep diary continuity variables. Studies are insufficient to evaluate the full impact on objective sleep variables. Measures of daytime functioning in response to therapy are lacking. Variability in the sleep restriction therapy implementation methods precludes any strong conclusions regarding the true impact of therapy. A future research agenda is outlined.

14 Review Acupuncture in the treatment of cancer-related psychological symptoms. 2014

Haddad, Nadia Elisabeth / Palesh, Oxana. ·Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA nhaddad@stanford.edu. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. ·Integr Cancer Ther · Pubmed #24501113.

ABSTRACT: Acupuncture is being adopted by cancer patients for a wide range of cancer-related symptoms including highly prevalent psychological symptoms like depression, anxiety, insomnia, and impairment in quality of life. Pharmacological treatment of prevalent symptoms like anxiety, depression, and sleep disturbance can contribute to the high chemical burden already carried by cancer patients, creating additional side effects. As a result, patients and providers alike are interested in evidence-based nonpharmacologic alternatives like acupuncture for these symptoms. This article reviews the current literature (January 2000 through April 2013) for acupuncture in cancer-related psychological symptoms with attention to both efficacy and acupuncture-specific methodology. All published studies that met our review criteria demonstrate a positive signal for acupuncture for the treatment of depression, anxiety, sleep disturbance, and for improving quality of life with most results showing statistical significance. However, there are only a handful of acupuncture studies that were specifically designed to evaluate depression, sleep disturbance, and quality of life as primary outcomes, and no studies were found that looked at anxiety as a primary outcome in this population. Published studies in cancer patients and survivors show that acupuncture treatment is not only safe but also more acceptable with fewer side effects than standard of care pharmacological treatments like antidepressants. Finally, there is wide variability in both the implementation and reporting of acupuncture methods in the literature, with only 2 of 12 studies reporting full details of acupuncture methods as outlined in the revised Standards for Reporting Interventions in Clinical Trials of Acupuncture guidelines, published in 2010 and providing an essential framework for the reporting of acupuncture methodology. This lack of methodological detail affects outcomes, generalizability, and validity of research involving acupuncture. Reasons for ongoing challenges in the development of high-quality acupuncture trials are discussed. In conclusion, results are encouraging for the development of randomized trials to directly evaluate the therapeutic impact of acupuncture in cancer-related psychological symptoms, including depression, anxiety, sleep disturbance, and quality of life, but attention to acupuncture methodological specific challenges in the development of high-quality research is necessary.

15 Review Non-pharmacological treatment of insomnia. 2012

Siebern, Allison T / Suh, Sooyeon / Nowakowski, Sara. ·Stanford University School of Medicine, Sleep Medicine Center, Redwood City, California 94063, USA. asiebern@stanford.edu ·Neurotherapeutics · Pubmed #22935989.

ABSTRACT: Insomnia is one of the most common sleep disorders, which is characterized by nocturnal symptoms of difficulties initiating and/or maintaining sleep, and by daytime symptoms that impair occupational, social, or other areas of functioning. Insomnia disorder can exist alone or in conjunction with comorbid medical and/or psychiatric conditions. The incidence of insomnia is higher in women and can increase during certain junctures of a woman's life (e.g., pregnancy, postpartum, and menopause). This article will focus on an overview of cognitive behavioral therapy for insomnia, evidence of effectiveness for this treatment when insomnia disorder is experienced alone or in parallel with a comorbidity, and a review with promising data on the use of cognitive behavioral therapy for insomnia when present during postpartum and menopause.

16 Review A review of sodium oxybate and baclofen in the treatment of sleep disorders. 2011

Brown, Mark A / Guilleminault, Christian. ·Stanford Sleep Medicine Center, Redwood City, CA 94063-5704, USA. mbrown8@stanford.edu ·Curr Pharm Des · Pubmed #21476957.

ABSTRACT: Studies examining GABA(B) receptor agonists have reported effects on sleep including decreased sleep onset latency (SOL), increased sleep consolidation and increases in slow wave sleep (SWS). γ-hydroxybutyrate (GHB) is proposed to act as a GABA(B) receptor agonist; however, the mechanism of action of GHB is controversial. In addition, the GABA(B) receptor agonist, baclofen, has also been proposed to exert similar effects on sleep. The aim of this paper is to provide a review of the human clinical studies of sodium oxybate and baclofen regarding sleep and the treatment of sleep disorders including narcolepsy and insomnia, as well as other disorders involving disrupted sleep such as fibromyalgia.

17 Review Hypocretin antagonists in insomnia treatment and beyond. 2011

Ruoff, Chad / Cao, Michelle / Guilleminault, Christian. ·Stanford Sleep Medicine Program, Stanford University School of Medicine, Redwood City, California, USA. cmruoff@gmail.com ·Curr Pharm Des · Pubmed #21476951.

ABSTRACT: Hypocretin neuropeptides have been shown to regulate transitions between wakefulness and sleep through stabilization of sleep promoting GABAergic and wake promoting cholinergic/monoaminergic neural pathways. Hypocretin also influences other physiologic processes such as metabolism, appetite, learning and memory, reward and addiction, and ventilatory drive. The discovery of hypocretin and its effect upon the sleep-wake cycle has led to the development of a new class of pharmacologic agents that antagonize the physiologic effects of hypocretin (i.e. hypocretin antagonists). Further investigation of these agents may lead to novel therapies for insomnia without the side-effect profile of currently available hypnotics (e.g. impaired cognition, confusional arousals, and motor balance difficulties). However, antagonizing a system that regulates the sleep-wake cycle while also influencing non-sleep physiologic processes may create an entirely different but equally concerning side-effect profile such as transient loss of muscle tone (i.e. cataplexy) and a dampened respiratory drive. In this review, we will discuss the discovery of hypocretin and its receptors, hypocretin and the sleep-wake cycle, hypocretin antagonists in the treatment of insomnia, and other implicated functions of the hypocretin system.

18 Review Insomnia and its effective non-pharmacologic treatment. 2010

Siebern, Allison T / Manber, Rachel. ·Sleep Medicine Center, Stanford University School of Medicine, 450 Broadway Street, M/C 5704, Redwood City, CA 94063, USA. Asiebern@stanford.edu ·Med Clin North Am · Pubmed #20451034.

ABSTRACT: Emerging data underscores the public health and economic burden of insomnia evidenced by increased health risks; increased health care utilization; and work domain deficits (absenteeism and reduced productivity). Cognitive behavioral therapy for insomnia (CBTi) is a brief and effective non-pharmacologic treatment for insomnia that is grounded in the science of sleep medicine and the science of behavior change and psychological theory, and in direct comparisons with sleep medication in randomized control trials that demonstrate that CBTi has comparable efficacy with more durable long-term maintenance of gains after treatment discontinuation. The high level of empirical support for CBTi has led the National Institutes of Health Consensus and the American Academy of Sleep Medicine Practice Parameters to make the recommendation that CBTi be considered standard treatment. The aim of this report is to increase awareness and understanding of health care providers of this effective treatment option.

19 Review Insomnia pharmacology. 2010

Sullivan, Shannon S. ·Stanford Sleep Medicine Center, Redwood City, CA, USA. shannon.s.sullivan@stanford.edu ·Med Clin North Am · Pubmed #20451033.

ABSTRACT: Insomnia is not only the most common sleep disorder in the population, it is a frequent complaint heard overall by primary care physicians and specialists alike. Given the high prevalence of this disorder, its tendency to persist, and the frequency with which patients complain of symptoms in practice, it is imperative to have an understanding of basic sleep-wake mechanisms and the evolving field of pharmacologic approaches to enhance sleep. Currently, pharmacologic approaches are among the most widely used therapies for insomnia. This article reviews sleep-wake mechanisms, the neuroanatomic targets for sleep and wake-promoting agents, and discusses currently used agents to promote sleep and investigational hypnotics.

20 Review Emerging treatments for narcolepsy and its related disorders. 2010

Nishino, Seiji / Okuro, Masashi. ·Stanford University School of Medicine, USA. nishino@Stanford.edu ·Expert Opin Emerg Drugs · Pubmed #20166851.

ABSTRACT: IMPORTANCE OF THE FIELD: Narcolepsy is a chronic sleep disorder, characterized by excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and nocturnal sleep disruption. Non-pharmacological treatments (i.e., behavioral modification) are often helpful for the clinical management of narcoleptic patients. As these symptoms are often disabling, most patients need life-long treatments. Over 90% of diagnosed narcoleptic patients are currently prescribed medications to control their symptoms; however, available treatments are merely symptomatic. AREAS COVERED IN THIS REVIEW: This review presents a description of the clinical symptoms of narcolepsy, followed by a discussion of the state-of-the-art knowledge regarding the disorder and related emerging treatments. In preparing this review, an extensive literature search was conducted using Pubmed. Only selected references from 1970 to 2008 are cited. WHAT THE READER WILL GAIN: This review focuses on emerging treatments for human narcolepsy, and the reader will gain significant knowledge of current and future treatment for this and related disorders. Traditionally, amphetamine-like stimulants (i.e., dopaminergic release enhancers) have been used for clinical management to improve EDS, and tricyclic antidepressants have been used as anticataplectics. However, treatments have recently evolved which utilize better tolerated compounds, such as modafinil (for EDS) and adrenergic/serotonergic selective reuptake inhibitors (as anticataplectics). In addition, night time administration of a short-acting sedative, gamma-hydroxybutyrate, has been used for the treatment for EDS and cataplexy. As a large majority of human narcolepsy is hypocretin peptide deficient, hypocretin replacement therapy may also be a new therapeutic option; yet, this option is still unavailable. In addition to the hypocretin-based therapy, a series of new treatments are currently being tested in animal and/or humans models. These potential options include novel stimulant and anticataplectic drugs as well as immunotherapy, based on current knowledge of the pathophysiology of narcolepsy with cataplexy. TAKE HOME MESSAGE: We expect that more pathophysiology-based treatments, capable of curing and/or preventing narcolepsy and related diseases, will be available in near future. As cases of EDS, associated with other neurological conditions (i.e., symptomatic narcolepsy or narcolepsy due to medical conditions), are often linked with hypocretin deficiency, these novel therapeutic options may also be applied to treatment of these disabling conditions.

21 Review Insomnia in the context of traumatic brain injury. 2009

Zeitzer, Jamie M / Friedman, Leah / O'Hara, Ruth. ·VA Palo Alto Health Care System, 3801 Miranda Avenue (151Y), Palo Alto, CA 94304, USA. jzeitzer@stanford.ed ·J Rehabil Res Dev · Pubmed #20104406.

ABSTRACT: Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality in the United States. One of the most common comorbidities of TBI is the disruption of normal sleep. While often viewed as a nuisance symptom, sleep disruption can delay TBI recovery and negatively affect many of the psychological (e.g., anxiety, depression) and neuromuscular (e.g., pain) sequelae of TBI, decreasing quality of life. Treatment of sleep disruption in the context of TBI is complicated by issues of an altered neuronal milieu, polypharmacy, and the complex relationship between the various comorbidities often found in patients with TBI. Given the growing number of veterans returning from combat with TBI and the elevated risk of comorbid disrupted sleep, both caused by and independent of TBI, a comprehensive review of sleep disruption and its treatment is of great relevance to the Department of Veterans Affairs.

22 Review Insomnia and depression: a multifaceted interplay. 2009

Manber, Rachel / Chambers, Andrea S. ·Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA 94305, USA. rmanber@stanford.edu ·Curr Psychiatry Rep · Pubmed #19909664.

ABSTRACT: Historically, insomnia has been viewed as a symptom of depressive illness that is expected to resolve with adequate treatment of the depressive disorder. This article reviews the evidence that increasingly challenges this simplistic view and summarizes research demonstrating the multifaceted interplay between insomnia and depression. It discusses the prevalence, clinical significance, and time course of insomnia, distinguishing between poor sleep and an insomnia disorder. The article also discusses abnormalities in sleep architecture in major depressive disorder and theories about the pathways connecting sleep and depression. It concludes with a discussion of issues related to treatment, including the effects of antidepressants on sleep and new evidence of the utility of adding an insomnia-specific therapy for improved management of depressed patients with comorbid insomnia.

23 Review Emerging drugs for insomnia: new frontiers for old and novel targets. 2009

Sullivan, Shannon S / Guilleminault, Christian. ·Stanford University Sleep Medicine Center, 450 Broadway Street, MC 5704, Redwood City, CA 94063, USA. ·Expert Opin Emerg Drugs · Pubmed #19708818.

ABSTRACT: BACKGROUND: Insomnia is the most prevalent sleep disorder, with up to 50% of the US adult population reporting symptoms of insomnia on a weekly basis and approximately 12% with insomnia disorder. Comorbid conditions such as depression and anxiety are frequent. Insomnia is more common with older age, female gender and socioeconomic status. Traditionally, therapy has focused on GABA(A) receptor agonists, and off-label antidepressant and antihistamine use. OBJECTIVE: With increased understanding of complex neural networks involved in sleep and wake, hypnotics are being developed to target a broader variety of receptors with increasing selectivity. This review summarizes promising compounds in Phase II and III trials with evidence supporting efficacy for treatment of insomnia. METHODS: 5-HT(2A) and 5-HT(2C) antagonists, melatonergic (MT1/MT2) agonists, orexin receptor (OX1/OX2) antagonists, as well as GABA(A) receptor agonists are reviewed and summarized. Data are collected from PubMed and Pharmaprojects database searches, company websites, recent scientific meeting presentations and abstracts. RESULTS/CONCLUSIONS: A variety of drugs targeting several pathways, including GABA(A) agonism, MT1/MT2 agonism, 5-HT(2A) antagonism, OX1/OX2 antagonism and others, are in Phase II and III trials. More work should be done to understand the impact of these drugs in certain populations and in the context of comorbid conditions.

24 Review Pediatric sleep pharmacology. 2008

Pelayo, Rafael / Dubik, Michael. ·Stanford Sleep Disorders Clinic, Stanford University School of Medicine, Stanford, CA 94305, USA. pelayo@stanford.edu ·Semin Pediatr Neurol · Pubmed #18555194.

ABSTRACT: This article reviews the most common pharmacologic options in the treatment of sleep disorders in children. Despite the high prevalence of sleep disorders in children, there is a paucity of education and information available on the pharmacologic management of sleep disorders in children. The principles of sleep physiology and pathophysiology that help provide more rational pharmacologic management are discussed. Medications are typically not Food and Drug Administration (FDA) approved for the pediatric age range or for the specific sleep disorder. Medications have a role for insomnia, narcolepsy, parasomnias, and sleep-related movement disorders. The available choices of hypnotics are reviewed. Medications to increase alertness of narcoleptics and decrease cataplexy are discussed. The use of dopaminergic agents for Restless Legs Syndrome is reviewed. The potential use of medication in sleep apnea is also reviewed. Pharmacologic guidelines need to be developed specifically for sleep disorders in children. Ideally, these guidelines should be FDA approved for the specific sleep disorder and for the pediatric age range. The development of easy to swallow, chewable or liquid forms of these medications are needed. Training programs should play the lead role in enhancing pediatricians' knowledge of the pharmacologic treatment of sleep disorders in children.

25 Clinical Trial The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy: an open-label extension study. 2010

Black, Jed E / Hull, Steven G / Tiller, Jane / Yang, Ronghua / Harsh, John R. ·Actelion Pharmaceuticals, Allschwil, Switzerland. jedblack@stanford.edu ·J Clin Sleep Med · Pubmed #20957846.

ABSTRACT: STUDY OBJECTIVES: Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. This study evaluated the tolerability and efficacy of armodafinil for > or = 12 months. METHODS: Patients with ES associated with treated OSA, SWD, or narcolepsy who completed one of four 12-week, double-blind studies were eligible for this multicenter, open-label study of > or = 12 months' duration of treatment with armodafinil (50 to 250 mg/day). Adverse events and other criteria of tolerability were monitored throughout the study. Efficacy assessments included the Clinical Global Impression of Change (CGI-C), Brief Fatigue Inventory (BFI), and Epworth Sleepiness Scale (ESS). RESULTS: Of 743 enrolled patients (474 with treated OSA, 113 with SWD, and 156 with narcolepsy), 57% of patients (420/743) completed 12 months or more of treatment. Discontinuations due to adverse events occurred in 13% of patients (95/743) during the initial 12-month period. Throughout the > or = 12-month study, adverse events were generally of mild-to-moderate intensity; headache (25% [180/731]), nasopharyngitis (17% [123/731]), and insomnia (14% [99/731]) were the most common. Modest increases were observed in vital sign measurements (blood pressure [3.6/2.3 mm Hg], heart rate [6.7 beats per minute]) across all patient groups; most of the changes occurred by month 3. Improvements from baseline in efficacy assessments started at month 1 and were maintained throughout the study. CONCLUSIONS: Armodafinil remained effective and was generally well tolerated. Increased monitoring of blood pressure may be appropriate in patients on armodafinil. Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy.