title: Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Study objectives were to determine (a) the relative efficacy of three doses of modafinil versus an active control dose of caffeine 600 mg; (b) whether modafinil effects are dose-dependent; and (c) the extent to which both agents maintain performance and alertness during the circadian trough.
  
  
  METHODS
  Fifty healthy young adults remained awake for 54.5 h (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 h awake), subjects received double blind administration of one of five drug doses: placebo; modafinil 100, 200, or 400 mg; or caffeine 600 mg ( n=10 per group), followed by hourly testing from midnight through 12:00 p.m. on day 3.
  
  
  RESULTS
  Performance and alertness were significantly improved by modafinil 200 and 400 mg relative to placebo, and effects were comparable to those obtained with caffeine 600 mg. Although a trend toward better performance at higher modafinil doses suggested a dose-dependent effect, 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 (nausea, heart pounding) were reported.
  
  
  CONCLUSIONS
  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 manifest. Thus, equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action. However, modafinil does not appear to 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.
authors.affiliation: Department of Neurobiology and Behaviour, Division of Neuropsychiatry, 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: Mary A
authors.initials: MA
authors.lastname: Kautz
authors.forename: David R
authors.initials: DR
authors.lastname: Thorne
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reichardt
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Balkin
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D001831:Body Temperature / Q000187:drug effects; D002110:Caffeine / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D002940:Circadian Rhythm / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D000077408:Modafinil; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D012892:Sleep Deprivation / Q000523:psychology; D012894:Sleep Stages / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D002110:Caffeine; D000077408:Modafinil