RESUMEN
INTRODUCTION: There is considerable individual variability in the ability to sustain performance during sleep loss. Preliminary evidence suggests that individuals with higher trait-like activation/functioning of the prefrontal cortex may be less vulnerable to fatigue. METHODS: We tested this hypothesis in a sample of 54 healthy volunteers who were assessed bi-hourly on a variant of the Psychomotor Vigilance Test during 41 h of sleep deprivation. A subset of these subjects, representing the top and bottom 25% of the sample based on their ability to sustain vigilance performance during sleep deprivation, were compared with respect to baseline neurocognitive abilities. RESULTS: The sleep deprivation Resistant group (N = 13) scored significantly higher than the sleep deprivation Vulnerable (N = 13) group on all three baseline tasks assessing prefrontal executive function abilities (letter fluency, Stroop Color-Word test, Color Trails Form 2), whereas no differences were found on non-executive function tasks. Similarly, groups showed no differences on demographic variables including age, education, hand preference, morningness-eveningness preference, global intellectual ability, or pre-study sleep history. DISCUSSION: Findings are consistent with the hypothesis that greater prefrontal/executive functioning may be protective against the adverse effects of sleep deprivation and suggest that baseline executive function testing may prove useful for prediction of resilience during sleep loss.
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Nivel de Alerta/fisiología , Desempeño Psicomotor/fisiología , Privación de Sueño/fisiopatología , Adulto , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
Prolonged sleep loss impairs alertness, vigilance and some higher-order cognitive and affective capacities. Some deficits can be temporarily reversed by stimulant medications including caffeine, dextroamphetamine, and modafinil. To date, only one study has directly compared the effectiveness of these three compounds and specified the doses at which all were equally effective in restoring alertness and vigilance following 64 h of wakefulness. The present study compared the effectiveness of these same three stimulants/doses following a less extreme period of sleep loss (i.e., 44 h). Fifty-three healthy adults received a single dose of modafinil 400 mg (n = 11), dextroamphetamine 20 mg (n = 16), caffeine 600 mg (n = 12), or placebo (n = 14) after 44 h of continuous wakefulness. After 61 h of being awake, participants obtained 12 h of recovery sleep. Psychomotor vigilance was assessed bi-hourly during waking and following recovery sleep. Relative to placebo, all three stimulants were equally effective in restoring psychomotor vigilance test speed and reducing lapses, although the duration of action was shortest for caffeine and longest for dextroamphetamine. At these doses, caffeine was associated with the highest percentage of subjectively reported side-effects while modafinil did not differ significantly from placebo. Subsequent recovery sleep was adversely affected in the dextroamphetamine group, but none of the stimulants had deleterious effects on postrecovery performance. Decisions regarding stimulant selection should be made with consideration of how factors such as duration of action, potential side-effects, and subsequent disruption of recovery sleep may interact with the demands of a particular operational environment.
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Nivel de Alerta/efectos de los fármacos , Atención/efectos de los fármacos , Compuestos de Bencidrilo/farmacología , Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Dextroanfetamina/farmacología , Desempeño Psicomotor/efectos de los fármacos , Privación de Sueño/psicología , Vigilia/efectos de los fármacos , Adolescente , Adulto , Compuestos de Bencidrilo/efectos adversos , Cafeína/efectos adversos , Estimulantes del Sistema Nervioso Central/efectos adversos , Computadoras de Mano , Dextroanfetamina/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Modafinilo , Polisomnografía/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Sueño/efectos de los fármacos , Adulto JovenRESUMEN
INTRODUCTION: Round-the-clock operations in both military and civilian sectors have increased the need for alertness- and performance-maintaining strategies. The potential performance and objective alertness-enhancing effects of CX717 (a novel cognitive enhancer currently being tested in Phase II clinical trials) were evaluated using a simulated night shift work paradigm. METHODS: In this randomized, double-blind, placebo-controlled, parallel groups design, 48 volunteers underwent 4 consecutive nights of simulated shift work. Each "shift" consisted of the following: at approximately 2145 (just prior to the start of each simulated night shift), volunteers ingested a single oral dose of CX717 200 mg, CX717 400 mg, CX717 1000 mg, or placebo (N = 12 per drug dosage). Performance, alertness, mood, and symptoms were then assessed from 2300 to 0700, followed by a polysomnographically monitored daytime sleep period from 0800 to 1200. RESULTS: Performance and alertness significantly degraded across the simulated night shifts (P < 0.05). None of the dosages of CX717 reversed these effects (P > 0.05). CX717 exerted some effects on daytime sleep, most notably reduction of slow-wave sleep time (P < 0.05). CX71 7 caused very few side effects and none of those were serious or unexpected. DISCUSSION AND CONCLUSIONS: At the doses tested, CX717 was not effective for reversing performance and alertness deficits associated with night shift work. Further work evaluating higher doses of CX717 may be warranted, as are studies in which CX717 effects are explored under other conditions (e.g., Alzheimer's dementia, attention deficit disorder).
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Nivel de Alerta/efectos de los fármacos , Ritmo Circadiano/efectos de los fármacos , Dioxoles/farmacología , Nootrópicos/farmacología , Piperidinas/farmacología , Trastornos del Sueño del Ritmo Circadiano/tratamiento farmacológico , Vigilia/efectos de los fármacos , Adolescente , Adulto , Análisis de Varianza , Método Doble Ciego , Empleo , Humanos , Masculino , Polisomnografía , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Antioxidantes/farmacología , Ritmo Circadiano , Hipnóticos y Sedantes/farmacología , Melatonina/farmacología , Desempeño Psicomotor/efectos de los fármacos , Piridinas/farmacología , Sueño/efectos de los fármacos , Adolescente , Adulto , Antioxidantes/administración & dosificación , Antioxidantes/análisis , Cognición/efectos de los fármacos , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Melatonina/administración & dosificación , Melatonina/análisis , Recuerdo Mental/efectos de los fármacos , Piridinas/administración & dosificación , Saliva/química , Vigilia/efectos de los fármacos , ZolpidemRESUMEN
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.