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

From the Guidelines

Pharmacologic therapy, including modafinil and armodafinil, is not currently supported by evidence and should not be prescribed as the primary treatment for obstructive sleep apnea (OSA) management. The American College of Physicians (ACP) recommends that all overweight and obese patients diagnosed with OSA should be encouraged to lose weight, as obesity is a risk factor for OSA, and evidence shows that intensive weight-loss interventions help reduce AHI scores and improve OSA symptoms 1.

Key Considerations

• Continuous positive airway pressure (CPAP) treatment is recommended as the initial therapy for patients diagnosed with OSA, particularly those with excessive daytime sleepiness, as it has been shown to improve ESS scores, reduce AHI and arousal index scores, and increase oxygen saturation 1.
• Mandibular advancement devices (MADs) can be considered as an alternative therapy to CPAP for patients who prefer MADs or have adverse effects associated with CPAP treatment, although evidence to suggest which patients would benefit most from MADs is insufficient 1.
• Adherence to therapies, especially CPAP, is important for effective OSA treatment, and clinicians should keep patient preferences and adherence, specific reasons for nonadherence, and costs in mind before initiating CPAP 1.

Clinical Implications

• Clinicians should 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.
• The effect of CPAP on other clinical outcomes, including hypertension, cardiovascular events, and death, is uncertain, and further research is needed to determine the long-term benefits of CPAP therapy 1.

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 2.
• Armodafinil is indicated to improve wakefulness in adult patients with excessive sleepiness associated with OSA, Narcolepsy, or Shift Work Disorder (SWD) 3.
• 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) 2.

From the Research

Efficacy of Modafinil and Armodafinil in Managing Excessive Daytime Sleepiness

• Modafinil and armodafinil have been shown to be effective in alleviating excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) 4, 5, 6, 7.
• A meta-analysis of randomized controlled trials found that modafinil and armodafinil significantly improved subjective and objective daytime sleepiness in patients with OSA 4.
• Another study found that modafinil improved daytime sleepiness in patients with mild to moderate OSA who were not using standard treatments, such as continuous positive airway pressure (CPAP) 6.
• Armodafinil has also been shown to improve wakefulness and memory in patients with OSA/hypopnea syndrome, and to reduce fatigue and the impact of sleepiness on daily activities 7.

Comparison of Modafinil and Armodafinil

• A study comparing the efficacy and safety of solriamfetol, modafinil, and armodafinil for EDS in OSA found that all three medications were associated with greater improvements than placebo on the Epworth Sleepiness Scale and the Maintenance of Wakefulness Test 5.
• The study also found that solriamfetol had the highest probabilities of improvement on these measures, followed by modafinil and armodafinil 5.

Clinical Guidance

• Residual EDS is a common problem in patients treated for OSA, and can persist despite normalization of breathing, oxygenation, and sleep quality with primary OSA therapy 8.
• Clinicians should be aware of the importance of assessing and managing EDS in patients with OSA, and should consider using various self-report and objective assessments to evaluate EDS 8.
• Pharmacotherapy, including modafinil and armodafinil, may be an effective option for managing EDS in patients with OSA 4, 5, 6, 7.