any adverse event; the most common being headache and nausea.2 While pharmacologic countermeasures play an impor- tant role, sleep experts have emphasized that behavioral and operational strategies remain foundational. “The most effective approaches are not pharmaco- logic—they’re behavioral, environmental, and systems- level,” said Michael Grandner, PhD, a sleep researcher at the University of Arizona and director of its Sleep and Health Research Program. Grandner, who was not involved in the review, emphasized that the goal is to reduce the need to “fight” sleep in the first place by pri- oritizing adequate sleep opportunity and minimizing cir- cadian disruption. When fatigue cannot be avoided, relatively simple interventions remain among the most effective, he said. “Short, planned naps, especially when paired with caffeine, consistently show meaningful improvements in alertness and performance,” Grandner said. Caffeine, he added, remains “the most scalable and evidence-based pharmacologic tool,” given its rapid onset, predictability and relative safety when used strategically. At the same time, both the review and Grandner emphasize an important limitation: no intervention fully restores performance to well-rested levels. As he noted, “the key point is that no intervention fully restores per- formance to well-rested levels,” underscoring the need for layered, multifaceted strategies rather than reliance on any single countermeasure. Individual Variability and Operational Constraints The review highlighted that the effectiveness of fatigue countermeasures is influenced by individual factors such as baseline sleep quality, circadian rhythm, and fatigue vulnerability. It also suggests that individuals more vulnerable to fatigue may derive greater benefit from stimulants. At the same time, operational constraints often limit the ability to implement ideal fatigue mitigation strat- egies. Military missions frequently require extended wakefulness or irregular schedules that cannot be eas- ily modified, reinforcing the need for flexible, adaptive approaches tailored to mission demands. The review also pointed to emerging technologies that may help address some of these challenges. Tools such as real-time fatigue monitoring—including eye- tracking and cognitive performance metrics—offer the potential to detect early signs of impairment and enable more proactive intervention. A Systems-Based Approach to Fatigue Management As the range of available countermeasures expands, there is growing recognition that fatigue management must be addressed at both the individual and system lev- els. Overreliance on pharmacologic interventions risks shifting responsibility away from operational factors such as scheduling, workload and mission design. Grandner noted that pharmacologic approaches often improve subjective alertness more than they restore full cognitive performance. “People feel more awake,” he told the Compendium of Federal Medicine, “but that can mask persistent deficits in higher-order functioning like judg- ment, decision-making, and risk assessment,” creating a risk of overconfidence in high-stakes environments. He also emphasized that these medications do not resolve the underlying biology of sleep loss. Instead, they might delay or blunt fatigue while allowing sleep debt to accumulate over time, potentially disrupting recovery and reinforcing schedules that are not physiologically sustainable. More broadly, Grandner warned of a systems-level con- cern: “instead of fixing schedules or reducing fatigue expo- sure, we ask individuals to compensate pharmacologically.” Ultimately, the review reinforced that no single inter- vention is sufficient. Effective fatigue management in mili- tary aviation requires a coordinated strategy that prioritizes sleep, integrates behavioral and pharmacologic approaches, and accounts for the realities of operational environments. The 2025 VA/DoD clinical guidelines for sleep apnea rec- ommend solriamfetol as a pharmacotherapy option for patients with OSA-related sleepiness. As new therapies and technologies continue to emerge, the challenge will be not only improving individual alertness but also designing systems that reduce fatigue risk at its source—ensuring that both performance and safety are maintained under demanding conditions. 1 Attiah Alzahrani A, Alessa MF, Musaad Alharbi F, Mohammed Alo- taibi T. Efficacy of Fatigue Countermeasures on Cognitive Performance and Operational Safety in Military Pilots: A Systematic Review. Cureus. 2025 Oct 31;17(10):e95823. doi: 10.7759/cureus.95823. PMID: 41328140; PMCID: PMC12665280. 2 Zitting KM, Gilmore KR, Lockyer BJ, Leary EB, et. Al. Solriamfetol for Excessive Sleepiness in Early-Morning Shift Work Disorder. NEJM Evid. 2026 Feb;5(2):EVIDoa2500190. doi: 10.1056/EVIDoa2500190. Epub 2026 Jan 27. PMID: 41590992. 2 0 2 6 C O M P E N D I U M O F F E D E R A L M E D I C I N E 8 5 Effective fatigue management requires a coordinated strategy.
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