Discussion
sleepiness, PVT, fatigue
MINOR
The present study demonstrates that 200 mg modafinil and 300 mg caffeine
significantly improve vigilance compared with placebo during an extended period of
continuous wakefulness (mean 17.3 h), including the WOCL, without causing side
effects. The most notable effects occurred in the early morning (between 4:00 and
6:00 AM), although PVT parameters improved as early as 2 h after administration. The
increase in vigilance with both modafinil and caffeine was confirmed by the PVT,
VigTrack, and SSS parameters. To our knowledge, this is the first randomized
placebo-controlled trial to demonstrate the beneficial effects of these
pharmaceutical agents after limited sleep deprivation.Our findings are in line with the literature, although previous studies investigated
the effects of caffeine and modafinil after longer periods of sustained wakefulness
(At Subjects did not always correctly identify which medication they had taken. In
slightly more than half of instances, they were correct. Approximately 25% of
subjects mistook modafinil for caffeine or vice versa, and 16–20% of subjects
mistook modafinil or caffeine for placebo. The effects of modafinil and caffeine
were more pronounced when interpreting the PVT scores than VigTrack parameters. This
may be explained by the difference in the difficulty of the tasks. The PVT is a
relatively simple task that is more sensitive to (feelings of) fatigue than
VigTrack. By contrast, VigTrack is a more complicated and challenging test that may
induce more motivation to perform and stay awake. Additionally, although both tests
are sensitive for measuring vigilance and alertness, they are not comparable to the
work load or complexity of tasks demanded of pilots in the cockpit. Performance
improvements are more pronounced in simulator studies than in in-flight testing
(Additionally, the effects found in this study may have been biased by the subjects’
level of caffeine consumption. Although the subjects ceased all caffeine consumption
from 5:00 PM on the test days, the effects of their habitual caffeine intake may
have still influenced their performance. Supplementary analysis is needed to
determine the effect of daily caffeine consumption on the effects of stimulants
during periods of sleep deprivation, and it may help to personalize stimulant use in
pilots. Conversely, minor aberrations in the manufacturing process could have
affected the results. While we believe these to be negligible, as the manufacturer
complied with national legislation and good clinical practice, we cannot rule this
out.Caffeine plasma concentrations measurements are in line with its pharmacokinetic
characteristics (Moreover, sleep-related factors were not considered in this study. Sleep deprivation
and also an extended period of wakefulness may negatively affect performance (In conclusion, both modafinil and caffeine improved vigilance and performance based
on the PVT and VigTrack, and resulted in a lower level of reported sleepiness after
a limited period of sleep deprivation. Modafinil was effective for longer than
caffeine, which is consistent with its longer half-life. The effects of both
modafinil and caffeine were noticeable approximately 2 h after drug administration.
The delayed effect of caffeine in comparison with its short
