• Yi-Chun Kuan, Dean Wu, Kuang-Wei Huang, Nai-Fang Chi, Chaur-Jong Hu, Chen-Chih Chung, Ka-Wai Tam, and Yao-Hsien Huang.
• Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Sleep Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: kelvintam@h.tmu.edu.tw.
• Clin Ther. 2016 Apr 1; 38 (4): 874-88.

PurposeObstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents known to be effective in alleviating sleepiness.MethodsWe performed a systematic review and meta-analysis of data from published randomized controlled trials (RCTs) that evaluated the efficacy of modafinil and armodafinil in treating EDS in patients with OSA. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on OSA published before October 2015.FindingsWe identified 11 RCTs of modafinil involving 723 patients and 5 RCTs of armodafinil involving 1009 patients. A pooled estimate of the mean differences in sleepiness parameters versus placebo were calculated using the random-effects model. Epworth Sleepiness Scale scores improved significantly in the modafinil group (weighted mean difference [WMD], -2.96 [95% confidence interval (CI), -3.73 to -2.19]) and in the armodafinil group (WMD, -2.63; 95% CI, -3.4 to -1.85) compared with those in the placebo group. Sleep latency, as measured on the Maintenance of Wakefulness Test, was significantly prolonged in the modafinil group (WMD, 2.51 [95% CI, 1.5-3.52]) and in the armodafinil group (WMD, 2.71 [95% CI, 0.04-5.37]). Patients tolerated the adverse events with both medications well.ImplicationsThe findings from our study suggest that both modafinil and armodafinil significantly improved subjective and objective daytime sleepiness. Thus, modafinil and armodafinil may be recommended to patients with OSA, particularly those with EDS.Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

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