What is the efficacy of Modafinil (modafinil) and Armodafinil (armodafinil) in managing Excessive Daytime Sleepiness (EDS) in patients with Obstructive Sleep Apnea (OSA)?

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Dainyal Siddiqui, MD

Internal Medicine

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Manuel Jimenez, MD

Cardiology

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Franz Pierre-Louis, MD

Infectious Disease

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Last updated: April 15, 2025 • View editorial policy

From the Guidelines

Pharmacologic therapy, including modafinil and armodafinil, is not currently supported by evidence and should not be prescribed for OSA treatment. The American College of Physicians guideline on management of OSA in adults recommends that clinicians target evaluation and treatment of OSA to patients with unexplained daytime sleepiness, and assessment of effectiveness is based primarily on improvement of daytime sleepiness 1, 2, 3, 4, 5.

Key Considerations

  • The primary treatment for OSA is continuous positive airway pressure (CPAP) therapy, which has been shown to improve ESS scores, reduce AHI and arousal index scores, and increase oxygen saturation 1, 2, 3, 4, 5.
  • Mandibular advancement devices (MADs) can be considered as an alternative therapy to CPAP for patients diagnosed with OSA who prefer MADs or for those with adverse effects associated with CPAP treatment 1, 2, 3, 4, 5.
  • Weight loss is also recommended for overweight and obese patients diagnosed with OSA, as it can help reduce AHI scores and improve OSA symptoms 1, 2, 3, 4, 5.

Evidence Summary

The evidence from the American College of Physicians guideline on management of OSA in adults suggests that pharmacologic agents, including modafinil and armodafinil, are not recommended for OSA treatment due to insufficient evidence supporting their use 1, 2, 3, 4, 5.

Clinical Implications

Clinicians should prioritize CPAP therapy and lifestyle modifications, such as weight loss, as the primary treatment for OSA, and consider MADs as an alternative therapy for patients who cannot tolerate CPAP. Pharmacologic therapy, including modafinil and armodafinil, should not be prescribed for OSA treatment due to the lack of evidence supporting their use.

From the FDA Drug Label

The effectiveness of modafinil tablets in improving wakefulness in patients with excessive sleepiness associated with OSA was established in two multi-center, placebo-controlled clinical studies of patients who met the criteria for OSA. The effectiveness of modafinil tablets in improving wakefulness in adult patients with excessive sleepiness associated with narcolepsy was established in two US 9-week, multi-center, placebo-controlled, parallel-group, double-blind studies of outpatients who met the criteria for narcolepsy Armodafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD).

Efficacy of Modafinil and Armodafinil:

  • Modafinil has been shown to be effective in improving wakefulness in patients with excessive sleepiness associated with Obstructive Sleep Apnea (OSA) and Narcolepsy 6.
  • Armodafinil is indicated to improve wakefulness in adult patients with excessive sleepiness associated with OSA, Narcolepsy, or Shift Work Disorder (SWD) 7.
  • Both Modafinil and Armodafinil have been demonstrated to be effective in managing excessive daytime sleepiness in patients with OSA, with Modafinil showing statistically significant improvement in the ability to remain awake compared to placebo-treated patients as measured by the Maintenance of Wakefulness Test (MWT) 6.

From the Research

Efficacy of Modafinil and Armodafinil

  • Modafinil and armodafinil have been shown to significantly improve subjective and objective daytime sleepiness in patients with obstructive sleep apnea (OSA) 8, 9, 10, 11.
  • The Epworth Sleepiness Scale scores improved significantly in the modafinil group (weighted mean difference, -2.96 [95% confidence interval, -3.73 to -2.19]) and in the armodafinil group (weighted mean difference, -2.63; 95% confidence interval, -3.4 to -1.85) compared with those in the placebo group 8.
  • Sleep latency, as measured on the Maintenance of Wakefulness Test, was significantly prolonged in the modafinil group (weighted mean difference, 2.51 [95% confidence interval, 1.5-3.52]) and in the armodafinil group (weighted mean difference, 2.71 [95% confidence interval, 0.04-5.37]) 8.

Safety and Tolerability

  • Patients tolerated the adverse events with both medications well 8, 10, 11.
  • Modafinil and armodafinil tripled adverse events and doubled adverse events leading to withdrawal but did not increase serious adverse events (hospitalizations or death) 11.
  • Less than 2% of patients using placebo or comparators experienced serious or discontinuation-related treatment-emergent adverse events 9.

Clinical Guidance

  • Modafinil and armodafinil may be recommended to patients with OSA, particularly those with excessive daytime sleepiness (EDS) 8, 12.
  • Clinicians may want to use the data to balance the risks and benefits on a case-by-case basis with their patients 11.
  • EDS is often overlooked and under-discussed in the primary care setting and in the follow-up of CPAP-treated patients, and a systematic approach to identify, evaluate, and manage EDS in patients treated for OSA is necessary 12.

References

9
Research

Indirect treatment comparison of solriamfetol, modafinil, and armodafinil for excessive daytime sleepiness in obstructive sleep apnea.

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2021

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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