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Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials

  • Yi-Chun Kuan
    Correspondence
    Address correspondence to: Yao-Hsien Huang, MD, Department of Neurology, Taipei Medical University-Shuang Ho Hospital, 291 Zhongzheng Road, Zhonghe District, New Taipei City, 23561, Taiwan. E-mail: [email protected] and Ka-Wai Tam, MD, Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, 291 Zhongzheng Road, Zhonghe District, New Taipei City, 23561, Taiwan.
    Affiliations
    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
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  • Dean Wu
    Affiliations
    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
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  • Kuang-Wei Huang
    Affiliations
    Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Department of Gastroenterology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
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  • Nai-Fang Chi
    Affiliations
    Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan

    Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
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  • Chaur-Jong Hu
    Affiliations
    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
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  • Chen-Chih Chung
    Affiliations
    Department of Neurology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan

    Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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  • Ka-Wai Tam
    Affiliations
    Center for Evidence-based Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Division of General Surgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
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  • Yao-Hsien Huang
    Affiliations
    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

    Brain and Consciousness Research Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
    Search for articles by this author

      Abstract

      Purpose

      Obstructive 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.

      Methods

      We 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.

      Findings

      We 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.

      Implications

      The 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.

      Key words

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