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Modafinil is a relatively new synthetic psychostimulant that has been shown to promote vigilance and arousal with apparently few physiological side effects. Accordingly, modafinil may provide a safe and effective alternative to the more commonly used amphetaminic class of stimulants, for example, in clinical settings to treat sleep disorders (e.g., idiopathic hypersomnia and narcolepsy) and sustained military operations to promote vigilance during periods of prolonged sleep deprivation. In this article, we investigate the relative effects of three doses of modafinil on fatigue and cognitive performance in a double-blind, placebo-controlled, 64-hr sleep-deprivation study. We observe a dose-related ordering on subjective measures of fatigue, motivation, subjective performance, and alertness following 4 min with eyes closed and on objective measures of serial reaction time, complex mental addition, and short-term memory. Specifically, 300 mg of modafinil in a 24-hr period (100 mg every 8 hr) was found to maintain cognitive performance at or near baseline levels throughout the sleep-deprivation period, 150 mg of modafinil in a 24-hr period (50 mg every 8 hr) provided some maintenance of performance, and 50 mg of modafinil in a 24-hr period (16.7 mg every 8 hr) was not substantively different from placebo. In addition, subjective reports made by the participants during weekly debriefings revealed no evidence of intolerance at any drug dose. Accordingly, these findings permit a specification of the minimum dose of modafinil required for the safe and effective amelioration of cognitive performance decrements induced by a period of prolonged sleep deprivation.
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