Abstract
Rationale
Caffeine is widely used as a countermeasure against neurobehavioral impairment during sleep deprivation. However, little is known about the pharmacodynamic profile of caffeine administered repeatedly during total sleep deprivation.
Objectives
To investigate the effects of repeated caffeine dosing on neurobehavioral performance during sleep deprivation, we conducted a laboratory-based, randomized, double-blind, placebo-controlled, crossover, multi-dose study of repeated caffeine administration during 48 h of sleep deprivation. Twelve healthy adults (mean age 27.4 years, six women) completed an 18-consecutive-day in-laboratory study consisting of three 48 h total sleep deprivation periods separated by 3-day recovery periods. During each sleep deprivation period, subjects were awakened at 07:00 and administered caffeine gum (0, 200, or 300 mg) at 6, 18, 30, and 42 h of wakefulness. The Psychomotor Vigilance Test and Karolinska Sleepiness Scale were administered every 2 h.
Results
The 200 and 300 mg doses of caffeine mitigated neurobehavioral impairment across the sleep deprivation period, approaching two-fold performance improvements relative to placebo immediately after the nighttime gum administrations. No substantive differences were noted between the 200 mg and 300 mg caffeine doses, and adverse effects were minimal.
Conclusions
The neurobehavioral effects of repeated caffeine dosing during sleep deprivation were most evident during the circadian alertness trough (i.e., at night). The difference between the 200 mg and 300 mg doses, in terms of the mitigation of performance impairment, was small. Neither caffeine dose fully restored performance to well-rested levels. These findings inform the development of biomathematical models that more accurately account for the time of day and sleep pressure–dependent effects of caffeine on neurobehavioral performance during sleep loss.
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Acknowledgements
The authors thank Walter Reed Army Institute of Research (WRAIR) for supplying the caffeine and placebo gum used in the study. They are grateful to Dr. Thomas Balkin of WRAIR for serving as the contracting officer’s technical representative. The authors also acknowledge the staff of the Human Sleep and Cognition Laboratory in the Sleep and Performance Research Center at Washington State University for their assistance in data collection.
Funding
This research was supported by Office of Naval Research grant N00014-15-1-0019. SR and JR were supported by the Military Operational Medicine Program Area Directorate of the US Army Medical Research and Materiel Command, Fort Detrick, MD.
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The study was approved by the Institutional Review Board (IRB) of Washington State University. Subjects gave written, informed consent prior to participation.
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The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army or of the US Department of Defense. This paper has been approved for public release with unlimited distribution.
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Hansen, D.A., Ramakrishnan, S., Satterfield, B.C. et al. Randomized, double-blind, placebo-controlled, crossover study of the effects of repeated-dose caffeine on neurobehavioral performance during 48 h of total sleep deprivation. Psychopharmacology 236, 1313–1322 (2019). https://doi.org/10.1007/s00213-018-5140-0
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DOI: https://doi.org/10.1007/s00213-018-5140-0