Medline ® Abstracts for References 1,88,89

BACKGROUND: Obstructive sleep apnea (OSA) is a common chronic disorder that often requires lifelong care. Available practice parameters provide evidence-based recommendations for addressing aspects of care.

OBJECTIVE: This guideline is designed to assist primary care providers as well as sleep medicine specialists, surgeons, and dentists who care for patients with OSA by providing a comprehensive strategy for the evaluation, management and long-term care of adult patients with OSA.

METHODS: The Adult OSA Task Force of the American Academy of Sleep Medicine (AASM) was assembled to produce a clinical guideline from a review of existing practice parameters and available literature. All existing evidence-based AASM practice parameters relevant to the evaluation and management of OSA in adults were incorporated into this guideline. For areas not covered by the practice parameters, the task force performed a literature review and made consensus recommendations using a modified nominal group technique.

RECOMMENDATIONS: Questions regarding OSA should be incorporated into routine health evaluations. Suspicion of OSA should trigger a comprehensive sleep evaluation. The diagnostic strategy includes a sleep-oriented history and physical examination, objective testing, and education of the patient. The presence or absence and severity of OSA must be determined before initiating treatment in order to identify those patients at risk of developing the complications of sleep apnea, guide selection of appropriate treatment, and to provide a baseline to establish the effectiveness of subsequent treatment. Once the diagnosis is established, the patient should be included in deciding an appropriate treatment strategy that may include positive airway pressure devices, oral appliances, behavioral treatments, surgery, and/or adjunctive treatments. OSA should be approached as a chronic disease requiring long-term, multidisciplinary management. For each treatment option, appropriate outcome measures and long-term follow-up are described.

STUDY OBJECTIVES: To perform a meta-analysis of the effect of wakefulness-promoting agents (modafinil and armodafinil) in patients with residual sleepiness after CPAP therapy for obstructive sleep apnea.

METHODS: We conducted a systematic search of MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014) and Cochrane Database for randomized placebo controlled trials on modafinil or armodafinil in patients who met established criteria for diagnosis of obstructive sleep apnea, adequate continuous positive airway pressure use, and who complained of residual sleepiness. Risk of bias was assessed. Primary outcomes were the Epworth Sleepiness Scale and mean sleep latencies on the maintenance of wakefulness test. Secondary outcomes were the Clinical Global Impression of Change, change in daily continuous positive airway pressure use, and the frequency of headaches.

RESULTS: Out of 118 abstracts screened and 12 full text articles reviewed, we included 6 studies (total of 1,479 participants) in our final meta-analysis: Three evaluated modafinil, and three armodafinil. Risk ofbias was unclear in one or more key domains for four studies. When compared with placebo, wakefulness promoting agents decreased Epworth Sleepiness Scale by 2.51 points (95% CI, 2.00-3.02), increased sleep latency in maintenance of wakefulness test by 2.73 minutes (95% CI, 2.12-3.34), increased the reporting of minimal improvement on the Clinical Global Impression of Change by 26% (RR 1.59; 95% CI, 1.36-1.86), and increased the risk of headaches by 8% (RR 1.98; 95% CI, 1.48-2.63). Also, there was a trend for decreased continuous positive airway pressure after treatment with these agents.

CONCLUSION: Wakefulness promoting agents improve objective and subjective measures of sleepiness, wakefulness, perception of disease severity in patients with residual sleepiness after CPAP therapy for OSA, and are generally well tolerated.

Modafinil is used internationally to treat residual sleepiness despite continuous positive airway pressure in obstructive sleep apnoea (res-OSA). In 2011, the European Medicines Agency removed the indication based on an unfavourable risk-benefit profile in two trials for efficacy and all accumulated safety data. We performed a meta-analysis of all randomised controlled trials of modafinil (or armodafinil) in res-OSA to quantify efficacy and safety.We systematically searched and assessed studies from major databases, conferences and trials registries to find randomised, placebo-controlled trials of modafinil/armodafinil for≥2 weeks in adult res-OSA treating sleepiness.We analysed 10 of the 232 articles identified that met inclusion criteria (1466 patients). Modafinil/armodafinil improved the Epworth Sleepiness Scale score (2.2 points, 95% CI 1.5-2.9) and the Maintenance of Wakefulness Test over placebo (3 min, 95% CI 2.1-3.8 min). Modafinil/armodafinil tripled adverse events and doubled adverse events leading to withdrawal but did not increase serious adverse events (hospitalisations or death).Modafinil and armodafinil improve subjective and objective daytime sleepiness in res-OSA. We believe our analysis is a fairer analysis of the risk-benefit profile of this indication. Clinicians may want to use this data to balance the risks and benefits on a case-by-case basis with their patients.