Wesensten, N. J., Belenky, G., Kautz, M. A., Thorne, D. R., Reichardt, R. M., & Balkinn, T. J. (2002). Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine. Psychopharmacology, 159(3), 238-247.

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"The performance and alertness effects of modafinil were evaluated to determine whether modafinil should replace caffeine for restoring performance and alertness during total sleep deprivation in otherwise healthy adults". This study determined (a) the relative efficacy of three doses of modafinil versus an active control dose of 600 mg of caffeine ; (b) whether modafinil effects are dose-dependent; and (c) the extent to which both agents maintain performance and alertness during the circadian trough. Healthy young adults (N = 50) remained awake for 54.5 hours (from 6:30 a.m. day 1 to 1:00 p.m. on day 3) and performance and alertness tests were administered bi-hourly from 8:00 a.m. day 1 until 10:00 p.m. day 2. At 11:55 p.m. on day 2 (after 41.5 hours awake), Ss received double blind administration of one of five drug doses: a placebo; 100, 200, or 400 mg of modafinil; or 600 mg of caffeine (N = 10 per group), followed by hourly testing from midnight through 12:00 p.m. on day 3.

Performance and alertness were significantly improved by 200 and 400 mg of modafinil relative to placebo, and effects were comparable to those obtained with 600 mg of caffeine. Differences between modafinil doses were not significant. Performance enhancing effects were especially salient during the circadian nadir (6:00 a.m. through 10:00 a.m.). Few instances of adverse subjective side effects (e.g., nausea, heart pounding) were reported. Equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action.

Implication. Like caffeine, modafinil maintained performance and alertness during the early morning hours, when the combined effects of sleep loss and the circadian trough of performance and alertness trough were manifested. Modafinil does not offer advantages over caffeine (which is more readily available and less expensive) for improving performance and alertness during sleep loss in otherwise normal, healthy adults. Modafinil is a banned substance while caffeine is not, but both have equivalent effects on performance. Since caffeine is not banned and its effects are tolerated it would seem that modafinil should be removed from the banned substance list.

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