Modafinil effects during acute continuous positive airway pressure withdrawal: a randomized crossover double-blind placebo-controlled trial

Rationale: Continuous positive airway pressure (CPAP) use is associated with reduced motor vehicle accidents in patients with obstructive sleep apnea (OSA). However, interruption of CPAP therapy is common and is associated with a decline in daytime function. Objectives: We hypothesized that the wakefulness promoter, modafinil, would ameliorate this decline. Methods: Patients were admitted to the laboratory for three consecutive nights. CPAP was used for the first night, followed by a baseline day, and was then withdrawn for the two subsequent nights (nasal airflow monitored). On each of the mornings after the two CPAP withdrawal nights, patients received 200 mg modafinil or placebo (n = 21) in a randomized, double-blind, crossover design. Treatment periods were separated by a 5-week washout. Driving simulator performance, neurocognitive performance, and subjective alertness were measured by the AusEd driving simulator, psychomotor vigilance task, and Karolinska Sleepiness Scale, respectively. Measurements and Main Results: During CPAP withdrawal, severe sleep-disordered breathing was evident and administration of modafinil improved simulated driving performance (steering variability, P < 0.0001; mean reaction time, P ≤ 0.0002; lapses, P ≤ 0.01 on a concurrent task), psychomotor vigilance task (mean 1/reaction time and lapses, both P < 0.0002), and subjective sleepiness (P < 0.01). Conclusions: Modafinil prevented the decline in simulated driving performance, neurocognitive performance, and subjective sleepiness in patients with OSA with acutely interrupted CPAP therapy. Clinical trial registered with the Australian New Zealand Clinical Trials Registry at www.anzctr.org.au (ACTRN12606000027516).