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.

Original languageEnglish
Pages (from-to)874-888
JournalClinical Therapeutics
DOIs
Publication statusAccepted/In press - 2016

Fingerprint

Obstructive Sleep Apnea
Meta-Analysis
Randomized Controlled Trials
Confidence Intervals
Wakefulness-Promoting Agents
Placebos
Continuous Positive Airway Pressure
Wakefulness
armodafinil
modafinil
PubMed
Sleep
Maintenance
Databases

Keywords

  • Armodafinil
  • Continuous positive airway pressure
  • Meta-analysis
  • Modafinil
  • Obstructive sleep apnea
  • Sleepiness

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{b9f40c187a134a01bc040381dbf5bfc8,
title = "Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-Analysis of Randomized Controlled Trials",
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.",
keywords = "Armodafinil, Continuous positive airway pressure, Meta-analysis, Modafinil, Obstructive sleep apnea, Sleepiness",
author = "Kuan, {Yi Chun} and Dean Wu and Huang, {Kuang Wei} and Nai-Fang Chi and Chaur-Jong Hu and Chung, {Chen Chih} and Ka-Wai Tam and Huang, {Yao Hsien}",
year = "2016",
doi = "10.1016/j.clinthera.2016.02.004",
language = "English",
pages = "874--888",
journal = "Clinical Therapeutics",
issn = "0149-2918",
publisher = "Excerpta Medica",

}

TY - JOUR

T1 - Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea

T2 - A Meta-Analysis of Randomized Controlled Trials

AU - Kuan, Yi Chun

AU - Wu, Dean

AU - Huang, Kuang Wei

AU - Chi, Nai-Fang

AU - Hu, Chaur-Jong

AU - Chung, Chen Chih

AU - Tam, Ka-Wai

AU - Huang, Yao Hsien

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Armodafinil

KW - Continuous positive airway pressure

KW - Meta-analysis

KW - Modafinil

KW - Obstructive sleep apnea

KW - Sleepiness

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