From the Guidelines
Modafinil is not a first-line treatment for obstructive sleep apnea (OSA), but it may be prescribed to help manage residual daytime sleepiness in patients already using primary treatments like CPAP therapy. Typically prescribed at doses of 100-200mg taken once daily in the morning, modafinil addresses excessive daytime sleepiness but does not treat the underlying breathing disruptions of sleep apnea. It's essential to understand that modafinil should only be used as an adjunctive therapy after optimizing primary treatments such as CPAP, which directly addresses the airway obstruction causing sleep apnea. Modafinil works by affecting certain neurotransmitters in the brain to promote wakefulness, but it doesn't improve nighttime breathing or oxygen levels. Potential side effects include headache, nausea, anxiety, and insomnia. Patients should be aware that modafinil may interact with certain medications and is contraindicated in some cardiac conditions. Regular follow-up with a sleep specialist is essential to monitor treatment effectiveness and adjust the overall sleep apnea management plan as needed, as recommended by the American Academy of Sleep Medicine 1.
Some key points to consider when using modafinil for OSA include:
- Modafinil is recommended for the treatment of residual excessive daytime sleepiness in OSA patients who have sleepiness despite effective PAP treatment and who are lacking any other identifiable cause for their sleepiness 1.
- The American College of Physicians recommends CPAP as the initial therapy for patients diagnosed with OSA, with mandibular advancement devices as an alternative therapy for patients who prefer them or have adverse effects associated with CPAP 2, 3, 4, 5, 6.
- Modafinil should not be used as a primary treatment for OSA, but rather as an adjunctive therapy to help manage residual daytime sleepiness, as pharmacologic therapy is not currently supported by evidence and should not be prescribed for OSA treatment 2, 3, 4, 5, 6.
- The most recent study from 2025 highlights the importance of a multidisciplinary approach to managing OSA, including the use of mandibular advancement devices and myofunctional therapy, but does not mention modafinil as a primary treatment option 7.
- A 2011 study recommends MADs for the treatment of patients with mild to moderate OSA and in patients who do not tolerate CPAP, but does not mention modafinil as a treatment option 8.
Overall, while modafinil may be useful in managing residual daytime sleepiness in patients with OSA, it should only be used as an adjunctive therapy after optimizing primary treatments such as CPAP, and under the guidance of a sleep specialist.
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. Patients treated with modafinil tablets showed a statistically significant improvement in the ability to remain awake compared to placebo-treated patients as measured by the MWT at final visit. A statistically significant greater number of patients treated with modafinil tablets showed improvement in overall clinical condition as rated by the CGI-C scale at final visit. In the second study, a 4-week trial, 157 patients with OSA were randomized to receive modafinil tablets 400 mg/day or placebo... At week 4, the ESS was reduced by 4.6 in the modafinil tablets group and by 2.0 in the placebo group, a difference that was statistically significant.
Modafinil is effective for treating excessive sleepiness associated with obstructive sleep apnea (OSA), as demonstrated by statistically significant improvements in wakefulness and clinical condition in two clinical studies 9.
- Key findings include: + Statistically significant improvement in ability to remain awake compared to placebo + Statistically significant improvement in overall clinical condition + Reduction in Epworth Sleepiness Scale (ESS) scores compared to placebo However, modafinil is not a treatment for the underlying obstruction in OSA, and CPAP should be used as the primary treatment 10.
From the Research
Efficacy of Modafinil in Treating Obstructive Sleep Apnea (OSA)
- Modafinil is approved for treating excessive daytime sleepiness associated with narcolepsy, shift-work sleep disorder, and as an adjunctive treatment in patients with obstructive sleep apnea syndrome who have residual daytime sleepiness despite optimal treatment with continuous positive airway pressure 11.
- Modafinil has been shown to improve measures of sleepiness in patients with OSA, but it may not normalize them, and its effectiveness compared to other stimulants is unclear 11.
- Wake-promoting agents, including modafinil, have demonstrated efficacy in reducing excessive daytime sleepiness and improving quality of life in patients with OSA 12, 13.
- Modafinil is recommended for patients who experience residual sleepiness despite optimal CPAP therapy, provided CPAP compliance is closely monitored 14.
Comparison with Other Wake-Promoting Agents
- A network meta-analysis evaluated the efficacy and safety of wake-promoting agents, including modafinil, for treating residual excessive daytime sleepiness in patients with OSA, and found that all agents demonstrated significant therapeutic benefits 15.
- The analysis ranked solriamfetol, pitolisant, modafinil, and armodafinil from highest to lowest for the Epworth sleepiness scale (ESS) and maintenance of wakefulness test (MWT) 15.
- The subgroup analysis evaluated the efficacy of wake-promoting agents in primary treatment adherent and nonadherent subgroups, and found that modafinil was effective in both groups 15.