Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

This guideline establishes clinical practice recommendations for the treatment of central disorders of hypersomnolence in adults and children. 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. 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. We recommend that clinicians use modafinil for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use pitolisant for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use sodium oxybate for the treatment of narcolepsy in adults. (STRONG). We recommend that clinicians use solriamfetol for the treatment of narcolepsy in adults. (STRONG). We suggest that clinicians use armodafinil for the treatment of narcolepsy in adults. (CONDITIONAL). We suggest that clinicians use dextroamphetamine for the treatment of narcolepsy in adults. (CONDITIONAL). We suggest that clinicians use methylphenidate for the treatment of narcolepsy in adults. (CONDITIONAL). We recommend that clinicians use modafinil for the treatment of idiopathic hypersomnia in adults. (STRONG). We suggest that clinicians use clarithromycin for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use methylphenidate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use pitolisant for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL). We suggest that clinicians use lithium for the treatment of Kleine-Levin syndrome in adults. (CONDITIONAL). We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to dementia with Lewy bodies in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of hypersomnia secondary to Parkinson's disease in adults. (CONDITIONAL). We suggest that clinicians use armodafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to traumatic brain injury in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to myotonic dystrophy in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of hypersomnia secondary to multiple sclerosis in adults. (CONDITIONAL). We suggest that clinicians use modafinil for the treatment of narcolepsy in pediatric patients. (CONDITIONAL). We suggest that clinicians use sodium oxybate for the treatment of narcolepsy in pediatric patients. (CONDITIONAL). Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2021;17(9):1881-1893.

This systematic review provides supporting evidence for the accompanying clinical practice guideline on the referral of adults with obstructive sleep apnea (OSA) for surgical consultation. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of upper airway sleep apnea surgery or bariatric surgery to no treatment as well as studies that reported on patient-important and physiologic outcomes pre- and postoperatively. Statistical analyses were performed to determine the clinical significance of using surgery to treat obstructive sleep apnea in adults. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search resulted in 274 studies that provided data suitable for statistical analyses. The analyses demonstrated that surgery as a rescue therapy results in a clinically significant reduction in excessive sleepiness, snoring, blood pressure (BP), apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI); an increase in lowest oxygen saturation (LSAT) and sleep quality; and an improvement in quality of life in adults with OSA who are intolerant or unaccepting of positive airway pressure (PAP) therapy. The analyses demonstrated that surgery as an adjunctive therapy results in a clinically significant reduction in optimal PAP pressure and improvement in PAP adherence in adults with OSA who are intolerant or unaccepting of PAP due to side effects associated with high pressure requirements. The analyses also demonstrated that surgery as an initial treatment results in a clinically significant reduction in AHI/RDI, sleepiness, snoring, BP, and ODI and an increase in LSAT in adults with OSA and major anatomical obstruction. Analysis of bariatric surgery data showed a clinically significant reduction in BP, AHI/RDI, sleepiness, snoring, optimal PAP level, BMI, and ODI and an increase in LSAT in adults with OSA and obesity. Analyses of very limited evidence suggested that upper airway surgery does not result in a clinically significant increase in risk of serious persistent adverse events and suggested that bariatric surgery may result in a clinically significant risk of iron malabsorption that may be managed with iron supplements. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Kent D, Stanley J, Aurora RN, etal. Referral of adults with obstructive sleep apnea for surgical consultation: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2021;17(12):2507-2531.

Clinical Guidelines for the Use of Unattended Portable Monitors in the Diagnosis of Obstructive Sleep Apnea in Adult Patients

The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of actigraphy. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of actigraphy, sleep logs, and/or polysomnography. Statistical analyses were performed to determine the clinical significance of using actigraphy as an objective measure of sleep and circadian parameters. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search resulted in 81 studies that met inclusion criteria; all 81 studies provided data suitable for statistical analyses. These data demonstrate that actigraphy provides consistent objective data that is often unique from patient-reported sleep logs for some sleep parameters in adult and pediatric patients with suspected or diagnosed insomnia, circadian rhythm sleep-wake disorders, sleep-disordered breathing, central disorders of hypersomnolence, and adults with insufficient sleep syndrome. These data also demonstrate that actigraphy is not a reliable measure of periodic limb movements in adult and pediatric patients. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.

Evidence Evaluation Process and Management of Potential Conflicts of Interest: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Lloyd R, Morgenthaler TI, Donald R, etal. Quality measures for the care of adult patients with obstructive sleep apnea: 2022 update after measure maintenance. J Clin Sleep Med. 2022;18(11):2673-2680.

Positive airway pressure (PAP) devices are used to treat patients with sleep related breathing disorders (SRBDs), including obstructive sleep apnea (OSA). After a patient is diagnosed with OSA, the current standard of practice involves performing attended polysomnography (PSG), during which positive airway pressure is adjusted throughout the recording period to determine the optimal pressure for maintaining upper airway patency. Continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BPAP) represent the two forms of PAP that are manually titrated during PSG to determine the single fixed pressure of CPAP or the fixed inspiratory and expiratory positive airway pressures (IPAP and EPAP, respectively) of BPAP for subsequent nightly usage. A PAP Titration Task Force of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Task Force developed these recommendations for conducting CPAP and BPAP titrations. Major recommendations are as follows: (1) All potential PAP titration candidates should receive adequate PAP education, hands-on demonstration, careful mask fitting, and acclimatization prior to titration. (2) CPAP (IPAP and/or EPAP for patients on BPAP) should be increased until the following obstructive respiratory events are eliminated (no specific order) or the recommended maximum CPAP (IPAP for patients on BPAP) is reached: apneas, hypopneas, respiratory effort-related arousals (RERAs), and snoring. (3) The recommended minimum starting CPAP should be 4 cm H2O for pediatric and adult patients, and the recommended minimum starting IPAP and EPAP should be 8 cm H2O and 4 cm H2O, respectively, for pediatric and adult patients on BPAP. (4) The recommended maximum CPAP should be 15 cm H2O (or recommended maximum IPAP of 20 cm H2O if on BPAP) for patients or = 12 years. (5) The recommended minimum IPAP-EPAP differential is 4 cm H2O and the recommended maximum IPAP-EPAP differential is 10 cm H2O (6) CPAP (IPAP and/or EPAP for patients on BPAP depending on the type of event) should be increased by at least 1 cm H2O with an interval no shorter than 5 min, with the goal of eliminating obstructive respiratory events. (7) CPAP (IPAP and EPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 1 obstructive apnea is observed for patients or = 12 years. (8) CPAP (IPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 1 hypopnea is observed for patients or = 12 years. (9) CPAP (IPAP for patients on BPAP) should be increased from any CPAP (or IPAP) level if at least 3 RERAs are observed for patients or = 12 years. (10) CPAP (IPAP for patients on BPAP) may be increased from any CPAP (or IPAP) level if at least 1 min of loud or unambiguous snoring is observed for patients or = 12 years. (11) The titration algorithm for split-night CPAP or BPAP titration studies should be identical to that of full-night CPAP or BPAP titration studies, respectively. (12) If the patient is uncomfortable or intolerant of high pressures on CPAP, the patient may be tried on BPAP. If there are continued obstructive respiratory events at 15 cm H2O of CPAP during the titration study, the patient may be switched to BPAP. (13) The pressure of CPAP or BPAP selected for patient use following the titration study should reflect control of the patient's obstructive respiration by a low (preferably 3 hr).

Narcolepsy type 1 (NT1) and type 2 (NT2) are two rare neurological diseases, classified as central disorders of hypersomnolence. The pathophysiology of NT1 is well known; it is caused by the selective destruction of hypocretin (Hcrt) neurons, by a highly suspected autoimmune process. On the contrary, little is known about NT2 etiology, sharing with NT1 somnolence and signs of dysregulation of rapid eye movement (REM) sleep, but not cataplexy. Management strategies are rather codified, at least in adults, with a lifelong treatment required in NT1, whereas no pharmacological study focused only on NT2 patients, with sometimes spontaneous improvement or disappearance of their symptoms. We recommend that medications and guidelines in NT2 should be the same as for NT1 (except for cataplexy), but the benefit risk ratio should be reassessed regularly. The main symptom in both diseases is a disabling excessive daytime sleepiness (EDS). First-line medications should be stimulants such as modafinil, armodafinil, or sodium oxybate, second-line methylphenidate and pitolisant, where available, and amphetamines as third-line therapy. Sodium oxybate has the advantage to be also effective to manage the fragmented nocturnal sleep, another common symptom in NT1. We advise to wait a few weeks with a stimulant drug before starting an anticataplectic treatment in NT1, except for severe cataplexy. Furthermore, cataplexy treatment should not be systematic. First-line strategy is the use of sodium oxybate, the only drug approved for cataplexy and EDS in adults. However, antidepressant agents such as venlafaxine are also commonly used, with few adverse effects and a good efficacy, although based on expert consensus only. A clinically relevant tool is required to quantify the severity of narcolepsy, subjective symptoms, and their consequences, to monitor the treatment efficacy, and to finally optimize narcolepsy management. In the future, Hcrt replacement or Hcrt agonists will certainly be options to treat NT1, but for now the different peptides do not cross easily the blood brain barrier. Immune-based therapies are other possibilities in NT1, at disease onset, with already some successful attempts to slow down or stop the autoimmune process.

This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central sleep apnea syndrome in adults. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of positive airway pressure therapies, non-positive airway pressure therapies, and pharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical meaningfulness of using various interventions to treat central sleep apnea in adults. The Grading of Recommendations Assessment, Development, and Evaluation process was used to assess the evidence for making recommendations. The literature search resulted in 6,701 articles, of which 103 articles provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Badr MS, Khayat RN, Allam JS, etal. Treatment of central sleep apnea in adults: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2025;21(12):2213-2236.

This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of restless legs syndrome and periodic limb movement disorder. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of pharmacological or nonpharmacological treatment to no treatment to improve patient-important outcomes. Statistical analyses were performed to determine the clinical significance of using various interventions to treat restless legs syndrome and periodic limb movement disorder in adults and children. The Grading of Recommendations Assessment, Development, and Evaluation process was used to assess the evidence for making recommendations. The literature search resulted in 3,631 studies out of which 148 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Winkelman JW, Berkowski JA, DelRosso LM, etal. Treatment of restless legs syndrome and periodic limb movement disorder: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2025;21(1):153-199.

The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on management of obstructive sleep apnea in medically hospitalized adults. The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials and observational studies that addressed interventions for the management of obstructive sleep apnea in medically hospitalized adults. Statistical analyses were performed to determine the clinical meaningfulness of critical and important outcomes. Finally, the Grading of Recommendations Assessment, Development, and Evaluation process was used to assess the evidence for making recommendations. The literature search resulted in 5,159 studies, out of which 27 studies provided data suitable for statistical analyses. The task force provided a detailed summary of the evidence along with the certainty of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations. Auckley DH, Mehra R, Johnson KG, etal. Evaluation and management of obstructive sleep apnea in adults hospitalized for medical care: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2025;21(12):2237-2256.

Actigraphy provides an objective measure of sleepiness and is recommended by the American Academy of Sleep Medicine for use 7-14 days prior to multiple sleep latency testing. It plays a valuable role in the differential diagnosis of hypersomnolence. Our aim was to provide a comprehensive summary of actigraphy features in central disorders of hypersomnolence (CDH). Data were sourced from six bibliographic databases. Fixed- or random-effects models were applied to compare patients with narcolepsy type 1 (NT1) to controls. Of the 1,737 publications identified in our search, 8 studies met the inclusion criteria. The total sample consisted of 473 participants, encompassing patients with NT1, idiopathic hypersomnia (IH), hypersomnolence with normal CSF hypocretin-1 levels, Kleine-Levin syndrome (KLS), traumatic brain injury (TBI), major depressive disorder (MDD), myotonic dystrophy (MD), primary insomnia and healthy controls. Actigraphy devices varied across studies. Compared to control subjects, NT1 patients had lower total sleep time (TST), sleep efficiency and daytime motor activity, with increased wake after sleep onset, awakenings, nocturnal motor activity and longest nap duration. In KLS, TST was higher during hypersomnia episodes than during asymptomatic phases. TBI and MDD patients had a higher TST than the control group, while MD patients had a lower TST than patients with IH. Actigraphy is a valuable tool for objectively assessing sleep and can assist in detecting CDH. However, the absence of standardized guidelines limits their broader implementation in clinical practice.

Excessive Daytime Sleepiness: A Clinical Review

Respiratory-related leg movements (RRLMs) may contribute to the cardiovascular risk associated with obstructive sleep apnea (OSA). Selective serotonin reuptake inhibitors (SSRIs), but not bupropion, increase periodic leg movements in sleep. This study examines whether patients with OSA using SSRIs have more RRLMs than those taking bupropion or no antidepressant. Patients with an apnea-hypopnea index (AHI) of at least 10 events/h during a full-night diagnostic study or split-night study, who were taking bupropion (n = 32), an SSRI (n = 31), or no antidepressant (n = 31), were selected from a database of prestudy questionnaires. RRLMs were scored according to World Association of Sleep Medicine 2016 standards. Patients using SSRIs had significantly greater overall RRLM% (defined as the percentage of respiratory events associated with a leg movement, including apneas, hypopneas, and respiratory effort-related arousals), RRLM index, and periodic limb movement index relative to patients using bupropion and control patients. The difference between the RRLM% in the SSRI and bupropion groups was limited to patients undergoing split-night studies, and that of the SSRI and control groups was limited to patients undergoing full-night diagnostic studies. The greater number of RRLMs and PLMs in the SSRI group may contribute to treatment-emergent insomnia often seen with SSRI use. Fragmented sleep and elevated autonomic nervous system activation associated with increased RRLMs in patients with OSA taking SSRIs might also limit the tolerability of antidepressant treatment, as well as increase the risk for cardiovascular disease.

The purpose of this systematic review is to provide supporting evidence for the clinical practice guideline for the treatment of obstructive sleep apnea (OSA) in adults using positive airway pressure (PAP). The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of PAP with no treatment as well as studies that compared different PAP modalities. Meta-analyses were performed to determine the clinical significance of using PAP in several modalities (ie, continuous PAP, auto-adjusting PAP, and bilevel PAP), to treat OSA in adults. In addition, meta-analyses were performed to determine the clinical significance of using an in-laboratory versus ambulatory strategy for the initiation of PAP, educational and behavioral interventions, telemonitoring, humidification, different mask interfaces, and flexible or modified pressure profile PAP in conjunction with PAP to treat OSA in adults. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations. The literature search resulted in 336 studies that met inclusion criteria; 184 studies provided data suitable for meta-analyses. The data demonstrated that PAP compared to no treatment results in a clinically significant reduction in disease severity, sleepiness, blood pressure, and motor vehicle accidents, and improvement in sleep-related quality of life in adults with OSA. In addition, the initiation of PAP in the home demonstrated equivalent effects on patient outcomes when compared to an in-laboratory titration approach. The data also demonstrated that the use of auto-adjusting or bilevel PAP did not result in clinically significant differences in patient outcomes compared with standard continuous PAP. Furthermore, data demonstrated a clinically significant improvement in PAP adherence with the use of educational, behavioral, troubleshooting, and telemonitoring interventions. Systematic reviews for specific PAP delivery method were also performed and suggested that nasal interfaces compared to oronasal interfaces have improved adherence and slightly greater reductions in OSA severity, heated humidification compared to no humidification reduces some continuous PAP-related side effects, and pressure profile PAP did not result in clinically significant differences in patient outcomes compared with standard continuous PAP.