Effect of Modafinil on Impairments in Neurobehavioral Performance and Learning Associated with Extended Wakefulness and Circadian Misalignment

Although worldwide millions of people work prolonged hours, at adverse circadian phases, evidence suggests that cognitive function is impaired under these conditions with important societal consequences. In a double-blind placebo-controlled laboratory-based study, we investigated the effect of the wakefulness-promoting drug modafinil as a countermeasure against such neurobehavioral impairments induced by both prolonged wakefulness and circadian misalignment. Neurobehavioral performance, alertness, and sleep were studied in young healthy participants (N = 18) who underwent a 25-day forced desynchrony protocol in which the period of the sleep-wakefulness cycle was scheduled to be 42.85 h (duration of each wakefulness episode: 28.57 h; sleep/rest episode: 14.28 h). Each waking day, participants were treated with either 400 mg modafinil, divided into three doses, or placebo, according to a randomized, parallel-group design. Treatment with modafinil significantly attenuated the performance decrements seen for several parameters including cognitive-psychomotor speed, visual attention and reaction times both with progressive hours awake and when working at adverse circadian phases. Subjective alertness and sleep parameters were similar between treatment groups, but modafinil-treated participants had fewer bouts of inadvertent sleep during scheduled waking. Modafinil reduced the neurobehavioral impairment associated with work, both during prolonged wakefulness and at adverse circadian phases, without adversely affecting subjective alertness or subsequent sleep. These features suggest that modafinil might be a particularly relevant countermeasure against the deleterious effects of prolonged work hours, shift work, and transmeridian travel. Neuropsychopharmacology (2010) 35, 1910-1920; doi: 10.1038/npp.2010.63; published online 26 May 2010