On Treatment but Still Sleepy
Purpose of review Although continuous positive airway pressure (CPAP) treatment effectively reduces sleepiness in obstructive sleep apnea (OSA) patients, some patients remain sleepy in spite of proper treatment. After exclusion or treatment of known causes of sleepiness, residual sleepiness may be diagnosed. Recent changes in approval for currently available wakefulness stimulants in Europe, development of new stimulants and questions about the reality of residual sleepiness prompted this review.
Recent findings Prevalence of residual sleepiness is approximately 10% and clearly decreases with increased nightly use of CPAP. Before treatment, patients with residual sleepiness are younger, suffer from less severe OSA and have worse health perception and mood than patients who respond to CPAP. Residual sleepiness is accompanied by other residual symptoms (e.g. fatigue, poor quality of life), suggesting the existence of a 'CPAP resistant syndrome'. Pathophysiological mechanisms remain unclear. Stimulant medication may be beneficial in some patients and is well tolerated.
Summary In spite of a substantial prevalence, residual sleepiness remains still poorly understood and may be difficult to treat. There remains a need for large prospective studies to better define predictive baseline characteristics and further research on causal mechanisms and pharmacological treatments, including large, long-term clinical trials of wakefulness stimulants, is needed.
Although not consistently present in patients with obstructive sleep apnea (OSA), excessive daytime sleepiness (EDS) is a frequent complaint of these patients and one of the criteria of the syndrome definition. EDS is usually defined on the basis of the Epworth Sleepiness Scale Score (ESS), with a score greater than 10 considered abnormal. Repeated episodes of pharyngeal collapse lead to sleep fragmentation and thus to sleepiness and daytime cognitive dysfunction. However, other mechanisms are likely to contribute to poor daytime vigilance in OSA. Abnormal sleep architecture, activation of the hypothalamic–pituitary–adrenal axis and inflammation markers and cytokine production are potential contributors. In addition, comorbid conditions, especially obesity, depression and voluntary sleep curtailment, may be present in OSA patients and thus complicate matters.
The presence of EDS, in particular if severe and/or in a patient with an at-risk occupation, is a compelling motive for recommending treatment with continuous positive airway pressure (CPAP). Furthermore, initial sleepiness is a predictor of CPAP treatment compliance. Randomized controlled trials comparing improvement in sleepiness for patients on effective compared with sham or placebo CPAP show a strong placebo effect. Nevertheless, the efficacy of CPAP in rapidly alleviating sleepiness has been demonstrated in controlled studies. Effective CPAP significantly reduces ESS score by approximately 3 points compared with sham CPAP. Unsurprisingly, the largest benefit is observed in patients with severe sleepiness at baseline. CPAP also significantly improves objective outcome measures of alertness and sleepiness, such as Maintenance of Wakefulness Test (MWT) and Oxford Sleep Resistance (OSLER) test latency, but the improvement is small. Functional outcomes, assessed with the Functional Outcomes of Sleep Questionnaire (FOSQ) and the SF-36, as well as mood disturbances, improve significantly on effective CPAP compared with sham CPAP. Yet, on follow-up visits, some OSA patients continue to complain of EDS while using CPAP.
Abstract and Introduction
Abstract
Purpose of review Although continuous positive airway pressure (CPAP) treatment effectively reduces sleepiness in obstructive sleep apnea (OSA) patients, some patients remain sleepy in spite of proper treatment. After exclusion or treatment of known causes of sleepiness, residual sleepiness may be diagnosed. Recent changes in approval for currently available wakefulness stimulants in Europe, development of new stimulants and questions about the reality of residual sleepiness prompted this review.
Recent findings Prevalence of residual sleepiness is approximately 10% and clearly decreases with increased nightly use of CPAP. Before treatment, patients with residual sleepiness are younger, suffer from less severe OSA and have worse health perception and mood than patients who respond to CPAP. Residual sleepiness is accompanied by other residual symptoms (e.g. fatigue, poor quality of life), suggesting the existence of a 'CPAP resistant syndrome'. Pathophysiological mechanisms remain unclear. Stimulant medication may be beneficial in some patients and is well tolerated.
Summary In spite of a substantial prevalence, residual sleepiness remains still poorly understood and may be difficult to treat. There remains a need for large prospective studies to better define predictive baseline characteristics and further research on causal mechanisms and pharmacological treatments, including large, long-term clinical trials of wakefulness stimulants, is needed.
Introduction
Although not consistently present in patients with obstructive sleep apnea (OSA), excessive daytime sleepiness (EDS) is a frequent complaint of these patients and one of the criteria of the syndrome definition. EDS is usually defined on the basis of the Epworth Sleepiness Scale Score (ESS), with a score greater than 10 considered abnormal. Repeated episodes of pharyngeal collapse lead to sleep fragmentation and thus to sleepiness and daytime cognitive dysfunction. However, other mechanisms are likely to contribute to poor daytime vigilance in OSA. Abnormal sleep architecture, activation of the hypothalamic–pituitary–adrenal axis and inflammation markers and cytokine production are potential contributors. In addition, comorbid conditions, especially obesity, depression and voluntary sleep curtailment, may be present in OSA patients and thus complicate matters.
The presence of EDS, in particular if severe and/or in a patient with an at-risk occupation, is a compelling motive for recommending treatment with continuous positive airway pressure (CPAP). Furthermore, initial sleepiness is a predictor of CPAP treatment compliance. Randomized controlled trials comparing improvement in sleepiness for patients on effective compared with sham or placebo CPAP show a strong placebo effect. Nevertheless, the efficacy of CPAP in rapidly alleviating sleepiness has been demonstrated in controlled studies. Effective CPAP significantly reduces ESS score by approximately 3 points compared with sham CPAP. Unsurprisingly, the largest benefit is observed in patients with severe sleepiness at baseline. CPAP also significantly improves objective outcome measures of alertness and sleepiness, such as Maintenance of Wakefulness Test (MWT) and Oxford Sleep Resistance (OSLER) test latency, but the improvement is small. Functional outcomes, assessed with the Functional Outcomes of Sleep Questionnaire (FOSQ) and the SF-36, as well as mood disturbances, improve significantly on effective CPAP compared with sham CPAP. Yet, on follow-up visits, some OSA patients continue to complain of EDS while using CPAP.
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