A double-blind, placebo-controlled investigation of the efficacy of modafinil for sustaining the alertness and performance of aviators: a helicopter simulator study

Rationale: In 1998, the FDA approved modafinil for treating excessive daytime sleepiness in narcoleptics, and this has raised questions about the appropriateness of this compound for enhancing alertness in sleep-deprived controls. This study explored the efficacy of modafinil for maintaining the performance of volunteers required to accomplish highly demanding tasks despite sleep loss. Objective: The principal objective was to determine whether prophylactic doses of modafinil would attenuate decrements in aviator performance and arousal throughout 2 days and 1 night without sleep. Methods: Six pilots were exposed to two 40-h periods of continuous wakefulness. In one, three 200-mg doses of modafinil were given and in the other, matching placebos were administered. Helicopter simulator flights, resting EEGs, and Profile of Mood States (POMS) questionnaires were evaluated. Results: Modafinil attenuated sleep deprivation effects on four of six flight maneuvers, reduced slow-wave EEG activity, and lessened self-reported problems with mood and alertness in comparison to placebo. The most noticeable benefits occurred between 0330 and 1130 hours, when the combined impact of sleep loss and the circadian trough was most severe. The most frequently observed drug side effects were vertigo, nausea, and dizziness. These could have been related to: 1) the motion-based testing, 2) the use of a simulator rather than an actual aircraft (i.e., "simulator sick ness"), and/or 3) the administration of more than 400 mg modafinil. Conclusions: Modafinil is a promising countermeasure for sleep loss in normals: however, additional studies aimed at reducing side effects are needed before it should be used in aviators.