title: Modafinil vs. caffeine: effects on fatigue during sleep deprivation.
abstract: BACKGROUND
  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).
  
  
  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.
authors.affiliation: Department of Behavioral Biology, Division of Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500, USA. nancy.wesensten@na.amedd.army.mil
authors.forename: Nancy Jo
authors.initials: NJ
authors.lastname: Wesensten
authors.forename: Gregory
authors.initials: G
authors.lastname: Belenky
authors.forename: David R
authors.initials: DR
authors.lastname: Thorne
authors.forename: Mary A
authors.initials: MA
authors.lastname: Kautz
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Balkin
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D002110:Caffeine / Q000494:pharmacology* / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005221:Fatigue / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D000077408:Modafinil; D011597:Psychomotor Performance / Q000187:drug effects*; D012892:Sleep Deprivation
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D002110:Caffeine; D000077408:Modafinil