The effect of modafinil following acute CPAP withdrawal: a preliminary study

Shaun C Williams, Naomi L Rogers, Nathaniel S Marshall, Stefanie Leung, Graham A Starmer, Ronald R Grunstein
Sleep & Breathing 2008, 12 (4): 359-64
Daytime symptoms resulting from obstructive sleep apnea (OSA) include impaired neurobehavioural performance and increased sleepiness. Continuous positive airway pressure (CPAP) reduces these symptoms. However, even compliant users may temporarily withdraw from CPAP treatment resulting in an immediate return of OSA. It has been hypothesised that these treatment "holidays" may be associated with neurobehavioural decline. Acute administration of a wakefulness promoter during such treatment "holidays" may help maintain neurobehavioural functioning. We examined the effects of 200 mg modafinil on neurobehavioural performance in a placebo-controlled crossover trial including N = 12 OSA patients acutely removed from CPAP. Sleep-wake activity was assessed for four consecutive days on CPAP and one night off CPAP using actigraphy. During the night off, CPAP patients wore a single channel nasal airflow diagnostic device. On the morning after CPAP withdrawal, patients reported to the laboratory and were administered either modafinil (200 mg) or placebo. At 2 h post-administration, patients completed a single simulated drive of approximately 30 min with simultaneous administration of a divided attention task (STISIMtrade mark), critical flicker fusion (CFF) test and subjective sleepiness scales. After a 14-day washout, participants repeated the protocol. CPAP withdrawal was associated with a worsening of sleep efficiency and the movement and fragmentation index (MFI), compared to the on-CPAP nights (all p < or = 0.02). Modafinil did not result in a superior driving simulator performance or CFF responses the morning after CPAP withdrawal but did result in better subjective sleepiness (both p < or = 0.04) compared to placebo. These data do not support the use of modafinil for the maintenance of daytime functioning in patients with OSA who are acutely withdrawn from CPAP.

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