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Neurotherapeutics : the Journal of the... Jan 2021There are numerous disorders of known or presumed neurologic origin that result in excessive daytime sleepiness, collectively known as the central disorders of... (Review)
Review
There are numerous disorders of known or presumed neurologic origin that result in excessive daytime sleepiness, collectively known as the central disorders of hypersomnolence. These include narcolepsy types 1 and 2, idiopathic hypersomnia, Kleine-Levin syndrome, and hypersomnia due to or associated with medical disease, neurologic disease, psychiatric disease, medications or substances, and insufficient sleep durations. This chapter focuses on the treatment of nonnarcoleptic hypersomnia syndromes, from those that are commonly encountered in neurologic practice, such as hypersomnia due to Parkinson's disease, to those that are exceedingly rare but present with dramatic manifestations, such as Kleine-Levin syndrome. The level of evidence for the treatment of sleepiness in these disorders is generally lower than in the well-characterized syndrome of narcolepsy, but available clinical and randomized, controlled trial data can provide guidance for the management of each of these disorders. Treatments vary by diagnosis but may include modafinil/armodafinil, traditional psychostimulants, solriamfetol, pitolisant, clarithromycin, flumazenil, sodium oxybate, melatonin, methylprednisolone, and lithium.
Topics: Central Nervous System Stimulants; Disorders of Excessive Somnolence; Humans; Idiopathic Hypersomnia; Wakefulness-Promoting Agents
PubMed: 32901432
DOI: 10.1007/s13311-020-00919-1 -
Sleep Medicine Reviews Jun 2023Idiopathic hypersomnia is a central hypersomnolence disorder of unknown origin characterized by excessive daytime sleepiness despite normal or long sleep time, and... (Review)
Review
Idiopathic hypersomnia is a central hypersomnolence disorder of unknown origin characterized by excessive daytime sleepiness despite normal or long sleep time, and frequent severe sleep inertia. Management strategies have been largely derived from expert consensus, due to a lack of disease-specific assessments and reliance on case series and rare randomized controlled studies. Guidelines recommend treatment with off-label medications. Modafinil, which was approved for idiopathic hypersomnia until 2011 in Europe, is the most commonly used treatment and improved sleepiness in two recent randomized placebo-controlled trials. In 2021, low-sodium oxybate (LXB) was approved in the United States for idiopathic hypersomnia. In a placebo-controlled, double-blind, randomized withdrawal study, LXB reduced daytime sleepiness and sleep inertia, and improved daily functioning. Here, treatment options are reviewed considering the authors' professional experience, current guidelines, and the latest research developments. The choice of pharmacotherapy should be guided by symptom profile, age, comorbidities (eg, depressive symptoms, cardiovascular problems), and concomitant medications (eg, oral contraceptives). Nonpharmacologic approaches have a role in management. An instrument (idiopathic hypersomnia severity scale) has been validated in idiopathic hypersomnia specifically, opening a path to better assessment of symptoms, impact, and response to treatment. Continued research on idiopathic hypersomnia is needed to support treatment algorithms.
Topics: Humans; Idiopathic Hypersomnia; Expert Testimony; Disorders of Excessive Somnolence; Modafinil; Sleep; Sodium Oxybate; Narcolepsy; Randomized Controlled Trials as Topic
PubMed: 36921459
DOI: 10.1016/j.smrv.2023.101766 -
Annals of the American Thoracic Society May 2021Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other... (Review)
Review
Many patients with obstructive sleep apnea (OSA) experience excessive daytime sleepiness (EDS), which can negatively affect daily functioning, cognition, mood, and other aspects of well-being. Although EDS can be reduced with primary OSA treatment, such as continuous positive airway pressure (CPAP) therapy, a significant proportion of patients continue to experience EDS despite receiving optimized therapy for OSA. This article reviews the pathophysiology and clinical evaluation and management of EDS in patients with OSA. The mechanisms underlying EDS in CPAP-treated patients remain unclear. Experimental risk factors include chronic intermittent hypoxia and sleep fragmentation, which lead to oxidative injury and changes in neurons and brain circuit connectedness involving noradrenergic and dopaminergic neurotransmission in wake-promoting regions of the brain. In addition, neuroimaging studies have shown alterations in the brain's white matter and gray matter in patients with OSA and EDS. Clinical management of EDS begins with ruling out other potential causes of EDS and evaluating its severity. Tools to evaluate EDS include objective and self-reported assessments of sleepiness, as well as cognitive assessments. Patients who experience residual EDS despite primary OSA therapy may benefit from wake-promoting pharmacotherapy. Agents that inhibit reuptake of dopamine or of dopamine and norepinephrine (modafinil/armodafinil and solriamfetol, respectively) have demonstrated efficacy in reducing EDS and improving quality of life in patients with OSA. Additional research is needed on the effects of wake-promoting treatments on cognition in these patients and to identify individual or disorder-specific responses.
Topics: Continuous Positive Airway Pressure; Disorders of Excessive Somnolence; Humans; Modafinil; Quality of Life; Sleep Apnea, Obstructive
PubMed: 33621163
DOI: 10.1513/AnnalsATS.202006-696FR -
Journal of Clinical Sleep Medicine :... Sep 2021This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
INTRODUCTION
This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children.
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to develop recommendations and assign strengths to each recommendation, based on a systematic review of the literature and an assessment of the evidence using the GRADE process. The task force provided a summary of the relevant literature and the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations that support the recommendations. The AASM Board of Directors approved the final recommendations.
RECOMMENDATIONS
The following recommendations are intended to guide clinicians in choosing a specific treatment for central disorders of hypersomnolence in adults and children. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation (ie, "We suggest…") is one that requires that the clinician use clinical knowledge and experience and strongly consider the individual patient's values and preferences to determine the best course of action. Under each disorder, strong recommendations are listed in alphabetical order followed by the conditional recommendations in alphabetical order. The section on adult patients with hypersomnia because of medical conditions is categorized based on the clinical and pathological subtypes identified in ICSD-3. The interventions in all the recommendation statements were compared to no treatment.
1
We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG).
2
We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG).
3
We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG).
4
We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG).
5
We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL).
6
We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL).
7
We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL).
8
We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG).
9
We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
10
We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
11
We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
12
We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL).
13
We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL).
14
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL).
15
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
16
We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL).
17
We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
18
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL).
19
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL).
20
We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL).
21
We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
22
We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL).
CITATION
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. . 2021;17(9):1881-1893.
Topics: Adult; Child; Disorders of Excessive Somnolence; Humans; Idiopathic Hypersomnia; Modafinil; Narcolepsy; Sleep; United States
PubMed: 34743789
DOI: 10.5664/jcsm.9328 -
Missouri Medicine 2018Adequate alertness is necessary for proper daytime functioning. Impairment of alertness or increase in sleepiness results in suboptimal performance and adversely affects... (Review)
Review
Adequate alertness is necessary for proper daytime functioning. Impairment of alertness or increase in sleepiness results in suboptimal performance and adversely affects the quality of life. While some causes of somnolence are intrinsic to the brain circuitry and neurochemical architecture, others are due to maladaptive behaviors and disorders affecting the normal sleep homeostasis. Identification of the problem and understanding the underlying etiology is the key to timely treatment and better outcomes.
Topics: Disorders of Excessive Somnolence; Humans; Sleep
PubMed: 30228690
DOI: No ID Found -
Continuum (Minneapolis, Minn.) Aug 2020This article discusses the central disorders of hypersomnolence, a group of disorders resulting in pathologic daytime sleepiness, particularly narcolepsy type 1 and... (Review)
Review
PURPOSE OF REVIEW
This article discusses the central disorders of hypersomnolence, a group of disorders resulting in pathologic daytime sleepiness, particularly narcolepsy type 1 and narcolepsy type 2, idiopathic hypersomnia, and Kleine-Levin syndrome. Disease features, diagnostic testing, epidemiology, pathophysiology, and treatment are reviewed.
RECENT FINDINGS
Increasing evidence implicates autoimmunity in narcolepsy type 1, including a strong association with human leukocyte antigen-DQB1*06:02, association with a polymorphism in the T-cell receptor alpha locus in genome-wide association, and the identification of autoreactive T cells in patients with this type of narcolepsy. In contrast, the cause or causes of narcolepsy type 2 and idiopathic hypersomnia are unknown. Multiple treatment options exist, including two medications approved for the treatment of narcolepsy by the US Food and Drug Administration (FDA) in 2019. These include solriamfetol, a dopamine- and norepinephrine-reuptake inhibitor, and pitolisant, an H3-inverse agonist/antagonist that increases histaminergic neurotransmission.
SUMMARY
The central disorders of hypersomnolence all cause severe sleepiness but can be differentiated based on ancillary symptoms, diagnostic testing, and pathophysiology. It is important that these disorders are identified because multiple treatments are available to improve functioning and quality of life.
Topics: Disorders of Excessive Somnolence; Humans
PubMed: 32756227
DOI: 10.1212/CON.0000000000000883 -
Dialogues in Clinical Neuroscience 2005Hypersomnia, a complaint of excessive daytime sleep or sleepiness, affects 4% to 6% of the population, with an impact on the everyday life of the patient Methodological... (Review)
Review
Hypersomnia, a complaint of excessive daytime sleep or sleepiness, affects 4% to 6% of the population, with an impact on the everyday life of the patient Methodological tools to explore sleep and wakefulness (interview, questionnaires, sleep diary, polysomnography, Multiple Sleep Latency Test, Maintenance of Wakefulness Test) and psychomotor tests (for example, psychomotor vigilance task and Oxford Sleep Resistance or Osler Test) help distinguish between the causes of hypersomnia. In this article, the causes of hypersomnia are detailed following the conventional classification of hypersomnic syndromes: narcolepsy, idiopathic hypersomnia, recurrent hypersomnia, insufficient sleep syndrome, medication- and toxin-dependent sleepiness, hypersomnia associated with psychiatric disorders, hypersomnia associated with neurological disorders, posttraumatic hypersomnia, infection (with a special emphasis on the differences between bacterial and viral diseases compared with parasitic diseases, such as sleeping sickness) and hypersomnia, hypersomnia associated with metabolic or endocrine diseases, breathing-related sleep disorders and sleep apnea syndromes, and periodic limb movements in sleep.
Topics: Circadian Rhythm; Disorders of Excessive Somnolence; Humans; Idiopathic Hypersomnia; Infections; Mental Disorders; Metabolic Diseases; Narcolepsy; Nervous System Diseases; Toxins, Biological
PubMed: 16416710
DOI: 10.31887/DCNS.2005.7.4/ydauvilliers -
Prague Medical Report 2021The review deals with idiopathic hypersomnia, focusing mostly on the research findings about the presence, onset and severity of excessive daytime sleepiness and... (Review)
Review
The review deals with idiopathic hypersomnia, focusing mostly on the research findings about the presence, onset and severity of excessive daytime sleepiness and depressive symptoms in patients with idiopathic hypersomnia.
Topics: Depression; Disorders of Excessive Somnolence; Humans; Idiopathic Hypersomnia
PubMed: 34606428
DOI: 10.14712/23362936.2021.13 -
The Neuroscientist : a Review Journal... Aug 2020Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis... (Review)
Review
Advances in neuroimaging open up the possibility for new powerful tools to be developed that potentially can be applied to clinical populations to improve the diagnosis of neurological disorders, including sleep disorders. At present, the diagnosis of narcolepsy and primary hypersomnias is largely limited to subjective assessments and objective measurements of behavior and sleep physiology. In this review, we focus on recent neuroimaging findings that provide insight into the neural basis of narcolepsy and the primary hypersomnias Kleine-Levin syndrome and idiopathic hypersomnia. We describe the role of neuroimaging in confirming previous genetic, neurochemical, and neurophysiological findings and highlight studies that permit a greater understanding of the symptoms of these sleep disorders. We conclude by considering some of the remaining challenges to overcome, the existing knowledge gaps, and the potential role for neuroimaging in understanding the pathogenesis and clinical features of narcolepsy and primary hypersomnias.
Topics: Animals; Disorders of Excessive Somnolence; Humans; Kleine-Levin Syndrome; Narcolepsy; Nervous System Diseases; Neuroimaging; Sleep
PubMed: 32111133
DOI: 10.1177/1073858420905829 -
BMC Medicine Mar 2013The associations between depressive symptoms and hypersomnia are complex and often bidirectional. Of the many disorders associated with excessive sleepiness in the... (Review)
Review
The associations between depressive symptoms and hypersomnia are complex and often bidirectional. Of the many disorders associated with excessive sleepiness in the general population, the most frequent are mental health disorders, particularly depression. However, most mood disorder studies addressing hypersomnia have assessed daytime sleepiness using a single response, neglecting critical and clinically relevant information about symptom severity, duration and nighttime sleep quality. Only a few studies have used objective tools such as polysomnography to directly measure both daytime and nighttime sleep propensity in depression with normal mean sleep latency and sleep duration. Hypersomnia in mood disorders, rather than a medical condition per se, is more a subjective sleep complaint than an objective finding. Mood symptoms have also been frequently reported in hypersomnia disorders of central origin, especially in narcolepsy. Hypocretin deficiency could be a contributing factor in this condition. Further interventional studies are needed to explore whether management of sleep complaints improves mood symptoms in hypersomnia disorders and, conversely, whether management of mood complaints improves sleep symptoms in mood disorders.
Topics: Depression; Disorders of Excessive Somnolence; Humans
PubMed: 23514569
DOI: 10.1186/1741-7015-11-78