Evaluation and management of residual sleepiness in obstructive sleep apnea
- Jean Louis Pepin, MD, PhD
Jean Louis Pepin, MD, PhD
- Professor of Clinical Physiology
- University Joseph Fourier
- Section Editors
- Nancy Collop, MD
Nancy Collop, MD
- Editor-in-Chief — Sleep Medicine
- Section Editor — Sleep Related Breathing Disorders
- Professor of Medicine and Neurology
- Director, Emory Sleep Center, Emory University
- Thomas E Scammell, MD
Thomas E Scammell, MD
- Section Editor — Hypersomnias
- Professor of Neurology, Beth Israel Deaconess Medical Center
- Boston Children's Hospital, and Harvard Medical School
Excessive daytime sleepiness (EDS) is one of the most common symptoms reported by patients with obstructive sleep apnea (OSA). While successful treatment of OSA with positive airway pressure (PAP) therapy or other modalities typically improves sleep quality, a small proportion of patients continue to experience EDS.
Patients with residual daytime sleepiness require careful evaluation to ensure proper functioning of positive airway pressure therapy or oral devices, adherence with primary therapy, and exclusion of alternative causes of EDS. In patients with adequately treated OSA and no additional explanations for residual sleepiness, symptomatic treatment with a wakefulness promoting drug may be beneficial.
The evaluation and management of residual sleepiness in adults with OSA is discussed here. Primary therapy for OSA (eg, PAP, oral appliances, or, occasionally, surgery) is discussed separately. (See "Management of obstructive sleep apnea in adults".)
Excessive daytime sleepiness (EDS) is defined as the inability to maintain wakefulness and alertness during the major waking episodes of the day, with sleep occurring unintentionally or at inappropriate times . In practice, EDS is often measured using the Epworth Sleepiness Scale (ESS), with scores greater than 10 generally considered abnormal (table 1) (calculator 1). The ESS does not capture all facets of sleepiness, however, and some patients who are sleepy may have a normal ESS score.
Residual sleepiness in patients with OSA refers to the subjective complaint of EDS that is present even when breathing and oxygenation parameters during sleep are normalized by successful OSA therapy. Although this definition of residual sleepiness is agreed upon, the entity itself is not universally accepted, as some experts feel that the prevalence of EDS in patients with successfully treated OSA simply reflects a prevalent complaint in the general population [2-4].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- American Academy of Sleep Medicine. International Classification of Sleep Disorders. In: Diagnostic and Coding Manual, 2nd ed, American Academy of Sleep Medicine, Westchester, IL 2005.
- Ohayon MM. Determining the level of sleepiness in the American population and its correlates. J Psychiatr Res 2012; 46:422.
- Pahwa P, Karunanayake CP, Hagel L, et al. Prevalence of High Epworth Sleepiness Scale scores in a rural population. Can Respir J 2012; 19:e10.
- Stradling JR. Residual sleepiness in patients with OSA on CPAP. Eur Respir J 2009; 34:1209.
- Gasa M, Tamisier R, Launois SH, et al. Residual sleepiness in sleep apnea patients treated by continuous positive airway pressure. J Sleep Res 2013; 22:389.
- Pépin JL, Viot-Blanc V, Escourrou P, et al. Prevalence of residual excessive sleepiness in CPAP-treated sleep apnoea patients: the French multicentre study. Eur Respir J 2009; 33:1062.
- Veasey SC, Davis CW, Fenik P, et al. Long-term intermittent hypoxia in mice: protracted hypersomnolence with oxidative injury to sleep-wake brain regions. Sleep 2004; 27:194.
- Zhan G, Fenik P, Pratico D, Veasey SC. Inducible nitric oxide synthase in long-term intermittent hypoxia: hypersomnolence and brain injury. Am J Respir Crit Care Med 2005; 171:1414.
- Zhang SX, Wang Y, Gozal D. Pathological consequences of intermittent hypoxia in the central nervous system. Compr Physiol 2012; 2:1767.
- Uysal A, Liendo C, McCarty DE, et al. Nocturnal hypoxemia biomarker predicts sleepiness in patients with severe obstructive sleep apnea. Sleep Breath 2014; 18:77.
- Mediano O, Barceló A, de la Peña M, et al. Daytime sleepiness and polysomnographic variables in sleep apnoea patients. Eur Respir J 2007; 30:110.
- Vernet C, Redolfi S, Attali V, et al. Residual sleepiness in obstructive sleep apnoea: phenotype and related symptoms. Eur Respir J 2011; 38:98.
- Koutsourelakis I, Perraki E, Economou NT, et al. Predictors of residual sleepiness in adequately treated obstructive sleep apnoea patients. Eur Respir J 2009; 34:687.
- Weaver TE, Maislin G, Dinges DF, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep 2007; 30:711.
- Stradling JR, Davies RJ. Is more NCPAP better? Sleep 2000; 23 Suppl 4:S150.
- Epstein LJ, Kristo D, Strollo PJ Jr, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 2009; 5:263.
- Hudgel DW, Thanakitcharu S. Pharmacologic treatment of sleep-disordered breathing. Am J Respir Crit Care Med 1998; 158:691.
- Morgenthaler TI, Kapen S, Lee-Chiong T, et al. Practice parameters for the medical therapy of obstructive sleep apnea. Sleep 2006; 29:1031.
- Kingshott RN, Vennelle M, Coleman EL, et al. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of residual excessive daytime sleepiness in the sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 2001; 163:918.
- Pack AI, Black JE, Schwartz JR, Matheson JK. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea. Am J Respir Crit Care Med 2001; 164:1675.
- Schwartz JR, Hirshkowitz M, Erman MK, Schmidt-Nowara W. Modafinil as adjunct therapy for daytime sleepiness in obstructive sleep apnea: a 12-week, open-label study. Chest 2003; 124:2192.
- Black JE, Hirshkowitz M. Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome. Sleep 2005; 28:464.
- Inoue Y, Takasaki Y, Yamashiro Y. Efficacy and safety of adjunctive modafinil treatment on residual excessive daytime sleepiness among nasal continuous positive airway pressure-treated japanese patients with obstructive sleep apnea syndrome: a double-blind placebo-controlled study. J Clin Sleep Med 2013; 9:751.
- Sukhal S, Khalid M, Tulaimat A. Effect of Wakefulness-Promoting Agents on Sleepiness in Patients with Sleep Apnea Treated with CPAP: A Meta-Analysis. J Clin Sleep Med 2015; 11:1179.
- Avellar AB, Carvalho LB, Prado GF, Prado LB. Pharmacotherapy for residual excessive sleepiness and cognition in CPAP-treated patients with obstructive sleep apnea syndrome: A systematic review and meta-analysis. Sleep Med Rev 2016; 30:97.
- Weaver TE, Chasens ER, Arora S. Modafinil improves functional outcomes in patients with residual excessive sleepiness associated with CPAP treatment. J Clin Sleep Med 2009; 5:499.
- Roth T, White D, Schmidt-Nowara W, et al. Effects of armodafinil in the treatment of residual excessive sleepiness associated with obstructive sleep apnea/hypopnea syndrome: a 12-week, multicenter, double-blind, randomized, placebo-controlled study in nCPAP-adherent adults. Clin Ther 2006; 28:689.
- Hirshkowitz M, Black JE, Wesnes K, et al. Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome. Respir Med 2007; 101:616.
- Hou RH, Langley RW, Szabadi E, Bradshaw CM. Comparison of diphenhydramine and modafinil on arousal and autonomic functions in healthy volunteers. J Psychopharmacol 2007; 21:567.
- Wong YN, Simcoe D, Hartman LN, et al. A double-blind, placebo-controlled, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers. J Clin Pharmacol 1999; 39:30.