Daytime sleep and performance following a zolpidem and melatonin cocktail.

STUDY OBJECTIVES: Pharmacologic enhancement of daytime sleep may help sustain optimal cognitive performance. At effective doses, zolpidem induces sleep but also impairs performance. Combining melatonin with low-dose zolpidem may promote daytime sleep without exacerbating performance impairments seen with high-dose zolpidem alone. DESIGN AND METHODS: Following an 8-hour undisturbed nighttime sleep period, 80 subjects (50 men, 30 women) were administered oral zolpidem 0, 5, 10, or 20 mg at 10:00 am (n = 20 per group) and then oral melatonin 0 or 5 mg at 10:30 am (thus, n = 10 per drug combination) in a double-blind randomized fashion. Subjects napped from 10:00 am to 11:30 am, at which time they were awakened and cognitive tests administered (Restricted Reminding, Paired-Associates, and Psychomotor Vigilance). A second nap ensued from 12:45 pm to 4:00 pm, followed immediately by further testing. RESULTS: Melatonin 5 mg plus zolpidem 0 mg enhanced daytime sleep (P < .05) with no memory or performance impairment (P > .05). Zolpidem 20 mg plus melatonin 0 mg also enhanced daytime sleep (albeit nonsignificantly), but memory and vigilance were impaired (P < .05). Melatonin's sleep-promoting effects were not evident until the second nap. CONCLUSIONS: No advantages to administering melatonin plus zolpidem "cocktails" were evident. Unlike zolpidem, melatonin 5 mg alone improved daytime sleep without impairing memory and vigilance. Functional coupling of sleep-inducing and memory-impairing effects may be specific to benzodiazepine-receptor agonists such as zolpidem, suggesting potential advantages to using melatonin in the operational environment. That melatonin's sleep-promoting effects were delayed for several hours presents a practical consideration that may limit melatonin's usefulness when daytime sleep periods cannot be reliably anticipated or planned in advance.

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.

Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine.

RATIONALE: 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. OBJECTIVES: 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.