Modafinil vs. caffeine: effects on fatigue during sleep deprivation.

INTRODUCTION: The extent to which modafinil and caffeine reverse fatigue effects (defined as performance decrements with time on task) during total sleep deprivation was investigated. METHODS: There were 50 healthy young adults who remained awake for 54.5 h (06:30 day 1 to 13:00 day 3). A 10-min vigilance test was administered bi-hourly from 08:00 day 1 until 22:00 day 2. At 23:55 day 2 (after 41.5 h awake), double-blind administration of one of five drug doses (placebo; modafinil 100, 200, or 400 mg; or caffeine 600 mg; n = 10 per group) was followed by hourly testing from 00:00 through 12:00 day 3. Response speed (reciprocal of reaction time) across the 10-min task (by 1-min block) was analyzed prior to and after drug administration. RESULTS: A fatigue effect (response speed degradation across the 10-min task) was exacerbated by sleep deprivation and circadian rhythmicity. Prior to the drug, this effect was maximal between 08:00 and 12:00 day 3 (24-28 h sleep deprivation). Modafinil 400 mg attenuated fatigue in a manner comparable to that seen with caffeine 600 mg; these effects were especially salient during the circadian nadir of performance (06:00 through 10:00); modafinil 200 mg also reversed fatigue, but for a shorter duration (3 min) than modafinil 400 mg (8 min) or caffeine 600 mg (6 min). DISCUSSION AND CONCLUSIONS: Time-on-task effects contributed to the performance degradation seen during sleep deprivation; effects which were reversed by caffeine and, at appropriate doses, by modafinil. Because the duration of efficacy for reversing time-on-task effects was shorter at lower drug dosages, the latter must be considered when determining the appropriate dose to use during sustained operations.