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What's new in sleep medicine

What's new in sleep medicine
April F Eichler, MD, MPH
Geraldine Finlay, MD
Alison G Hoppin, MD
Literature review current through: Nov 2022. | This topic last updated: Dec 12, 2022.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.


Position statement on obstructive sleep apnea in the transportation industry (October 2022)

The American Academy of Sleep Medicine (AASM) has published a position statement on recognizing and treating obstructive sleep apnea (OSA) in commercial drivers and other individuals in safety-sensitive transportation occupations [1,2]. The documents outline roles for key stakeholders, including legislators, employers, law enforcement, payers, health care professionals, and vehicle operators. The AASM recommends that commercial drivers be referred to a sleep medicine specialist for clinical sleep evaluation and diagnostic testing in the presence of a body mass index (BMI) ≥40 kg/m2, fatigue or sleepiness while on duty, involvement in a sleepiness-related crash or accident, or a BMI ≥33 kg/m2 plus either type 2 diabetes or hypertension requiring two or more medications. (See "Drowsy driving: Risks, evaluation, and management", section on 'Special considerations in commercial drivers'.)

Positive airway pressure therapy for obstructive sleep apnea in patients with COPD (August 2022)

Up to one-third of patients with chronic obstructive pulmonary disease (COPD) have coexisting obstructive sleep apnea (OSA); similar to the general population, positive airway pressure (PAP) is the mainstay of therapy, but outcomes in this population have not been assessed in large studies. In a health insurance claims database study of 6810 patients with COPD and OSA who were prescribed PAP, adherence was assessed with PAP user data, and propensity score matching was used to control for confounding [3]. During two years of PAP therapy, compared with the year before therapy, PAP-adherent patients showed greater reductions in emergency department visits, inpatient hospitalizations, and severe acute exacerbations compared with nonadherent patients. While randomized trials in patients with COPD are needed, these results support the ability of PAP to improve patient-important outcomes. (See "Sleep-related breathing disorders in COPD", section on 'Initiating positive airway pressure'.)

Carbonic anhydrase inhibition with sulthiame for treatment of sleep apnea (August 2022)

There is considerable interest in pharmacologic therapies for patients with obstructive sleep apnea (OSA) since intolerance to positive airway pressure (PAP) is common. In a trial of 56 patients with moderate or severe OSA who were PAP intolerant, the carbonic anhydrase inhibitor sulthiame at 200 or 400 mg per night improved OSA control, as evidenced by a significant reduction in the apnea hypopnea index during sleep (eg, from 61 to 41 events per hour on 200 mg; placebo 50.9 events per hour) [4]. Intermittent paraesthesias were common, and 11 percent of patients withdrew due to side effects when on the higher dose of sulthiame. Sulthiame is currently not available in the United States. Further studies are required before it can be used routinely in patients with OSA. (See "Management of obstructive sleep apnea in adults".)


Risk of drug overdose in young people prescribed benzodiazepines for sleep disorders (December 2022)

Prescription database studies indicate that benzodiazepines are commonly prescribed for insomnia, despite risks and the availability of safer options. In a recent cohort study in the United States that included over 90,000 children and young adults (age 10 to 29 years) with a sleep disorder who were prescribed a new insomnia medication, benzodiazepines were associated with increased risk of drug overdose in the next six months compared with alternative insomnia medications (trazodone, hydroxyzine, zolpidem, zaleplon, eszopiclone) [5]. Risk was highest among individuals who had also received an opioid prescription in the preceding three months. We do not prescribe benzodiazepines for insomnia in patients taking opioids or in those with a substance use disorder. (See "Pharmacotherapy for insomnia in adults", section on 'Shared warnings and precautions'.)

Network meta-analysis of insomnia medications in adults (July 2022)

A large number of medications spanning multiple classes are available for treatment of insomnia, but few long-term or comparative trials have been performed. This was illustrated by a network meta-analysis, which identified 154 placebo-controlled randomized trials of 30 different medications for insomnia in nearly 45,000 participants, of which only five trials were longer than four weeks, and nearly all comparisons relied on indirect evidence and a small subset of the total number of trials [6]. While the study concluded that eszopiclone, a benzodiazepine receptor agonist (BZRA), and lemborexant, a dual orexin receptor antagonist (DORA), appeared to be the most favorable medications for overall efficacy and tolerability, confidence was limited by known adverse effects of BZRAs and inconclusive long-term safety data for DORAs. In addition, patients with insomnia seen in clinical practice represent a broader population than those enrolled in clinical trials, and treatment decisions must weigh individual risks and benefits of medications along with all other available therapies. (See "Pharmacotherapy for insomnia in adults", section on 'Our approach'.)


Incidence of isolated sleep paralysis in the general population (September 2022)

Episodes of sleep paralysis, in which individuals awaken during rapid eye movement (REM) sleep and are temporarily unable to move or call out, are a classic feature of narcolepsy but can also occur as an isolated phenomenon. The incidence in otherwise healthy adults has not been well defined, however. In a representative sample of the United States population that included >12,000 adults, 10 percent reported having had one or more episodes of sleep paralysis in the past year [7]. Risk factors included sleep deprivation, younger age, posttraumatic stress disorder, chronic pain, and depression. Patients who report sleep paralysis should be queried for other signs of narcolepsy (eg, excessive daytime sleepiness, cataplexy) but in their absence, reassured about the benign nature of these events. (See "Approach to abnormal movements and behaviors during sleep", section on 'During REM sleep'.)

New proposed guidelines for rapid eye movement sleep behavior disorder (July 2022)

The International Rapid Eye Movement (REM) Sleep Behavior Disorder (RBD) Study Group has proposed new guidelines for RBD that include standardized definitions, physiologic recording parameters, and scoring criteria on video polysomnography (PSG) based on published studies and expert opinion [8]. The guidelines are intended to harmonize collection and interpretation of video PSG data in patients with clinical and prodromal RBD. Further studies are needed to determine the utility of these guidelines compared with current standard criteria delineated by the American Academy of Sleep Medicine scoring manual. (See "Polysomnography in the evaluation of parasomnias and epilepsy", section on 'REM sleep behavior disorder'.)

Dosing of dopamine agonists for restless legs syndrome (June 2022)

Dopamine agonists (eg, pramipexole, ropinirole) are an effective treatment for restless legs syndrome (RLS) but require monitoring and precautions to avoid serious side effects such as confusion, excessive daytime sleepiness, and impulse control disorders. Use of higher doses also increases the risk of paradoxical worsening of RLS symptoms (augmentation). In a United States prescription database study that included nearly 400,000 patients with RLS receiving treatment with dopamine agonists, 19 percent of patients were prescribed higher than recommended doses of dopamine agonists for RLS [9]. To reduce the risk of augmentation and other side effects, doses for RLS should not generally exceed the limits in the table (table 1); effective doses for RLS are lower than those used in Parkinson disease. (See "Management of restless legs syndrome and periodic limb movement disorder in adults", section on 'Side effects and monitoring'.)


ZSCAN1 autoantibodies in patients with ROHHAD syndrome (September 2022)

ROHHAD (Rapid-onset Obesity, Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation) is a rare syndrome of unknown etiology affecting young children; in approximately one-half of reported cases, patients are found to have peripheral neuroblastic tumors, suggesting a possible paraneoplastic mechanism. In a new study, novel zinc finger and SCAN domain-containing protein 1 (ZSCAN1) autoantibodies were identified in cerebrospinal fluid and/or serum in 7 out of 9 patients with ROHHAD and 0 out of 125 controls [10]. Additional studies confirmed ZSCAN1 expression in tumors of affected patients as well as in hypothalamic tissue lysates from healthy human brain. Further studies are needed to validate these findings; a few case reports have described some success with immunosuppressive therapy, particularly rituximab and cyclophosphamide. (See "Congenital central hypoventilation syndrome and other causes of sleep-related hypoventilation in children", section on 'Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD)'.)

  1. Das AM, Chang JL, Berneking M, et al. Obstructive sleep apnea screening, diagnosis, and treatment in the transportation industry. J Clin Sleep Med 2022; 18:2471.
  2. Das AM, Chang JL, Berneking M, et al. Enhancing public health and safety by diagnosing and treating obstructive sleep apnea in the transportation industry: an American Academy of Sleep Medicine position statement. J Clin Sleep Med 2022; 18:2467.
  3. Sterling KL, Pépin JL, Linde-Zwirble W, et al. Impact of Positive Airway Pressure Therapy Adherence on Outcomes in Patients with Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2022; 206:197.
  4. Hedner J, Stenlöf K, Zou D, et al. A Randomized Controlled Clinical Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnea. Am J Respir Crit Care Med 2022; 205:1461.
  5. Bushnell GA, Gerhard T, Keyes K, et al. Association of Benzodiazepine Treatment for Sleep Disorders With Drug Overdose Risk Among Young People. JAMA Netw Open 2022; 5:e2243215.
  6. De Crescenzo F, D'Alò GL, Ostinelli EG, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet 2022; 400:170.
  7. Ohayon MM, Pakpour AH. Prevalence, incidence, evolution and associated factors of sleep paralysis in a longitudinal study of the US general population. Sleep Med 2022; 98:62.
  8. Cesari M, Heidbreder A, St Louis EK, et al. Video-polysomnography procedures for diagnosis of rapid eye movement sleep behavior disorder (RBD) and the identification of its prodromal stages: guidelines from the International RBD Study Group. Sleep 2022; 45.
  9. Winkelman JW. High national rates of high-dose dopamine agonist prescribing for restless legs syndrome. Sleep 2022; 45.
  10. Mandel-Brehm C, Benson LA, Tran B, et al. ZSCAN1 Autoantibodies Are Associated with Pediatric Paraneoplastic ROHHAD. Ann Neurol 2022; 92:279.
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