Empirical data show that over 60% of military pilots report moderate to severe fatigue during operations, and fatigue has been implicated in up to 20% of avi- ation-related incidents and human factor errors in military contexts.” Pharmacologic Countermeasures: Benefits and Limitations Pharmacologic interventions have long been used in military settings to sustain wakefulness during extended operations. The review found that modafinil can improve vigilance and reduce subjective sleepiness, with observational data suggesting benefit across a range of operational scenarios. However, these effects are incom- plete. Even in controlled studies, neither modafinil nor other agents fully restored flight performance following significant sleep deprivation, highlighting the limits of pharmacologic compensation. According to the review, caffeine is among the most consistently effective fatigue countermeasures, with evidence showing improvements in vigilance, reaction time, and situational awareness. Its rapid onset and acces- sibility make it a practical option in operational settings. Although not addressed in the review, the effects of newer wake-promoting agents are also being explored. Solriamfetol, marketed as Sunosi, is Food and Drug Administration-approved for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea, has been shown in clinical studies to produce sustained wake-promoting effects for up to 7 to 9 hours after dosing. This longer duration of action, compared with modafinil, might offer advantages in extended operations or long- duration missions, although evidence in military or oper- ational settings remains limited at this point. While not in a military setting, a study published in NEJM Evidence earlier this year looked at solriamfetol for excessive sleepiness in early-morning shift work disorder. Brigham and Women’s Hospital-led researchers evalu- ated the efficacy of solriamfetol, a selective dopamine and norepinephrine reuptake inhibitor, for treating excessive sleepiness in 78 early-morning shift workers (shift start- ing between 3 a.m. and 7 a.m.) with excessive sleepiness associated with SWD. They found that, after 4 weeks, patients treated with solriamfetol were significantly less sleepy than those treated with placebo (9.4-minute longer sleep latency; 95% confidence interval [CI], 5.7 to 13.0; P<0.001). Solriamfetol treatment was associated with changed subjective sleepiness (Karolinska Sleepiness Scale dif- ference, -1.2; 95% CI, -1.7 to -0.7) and changed clini- cian (odds ratio 3.7; 95% CI, 1.3 to 10.4) and patient (odds ratio, 4.2; 95% CI, 1.5 to 11.6) ratings. Overall, 55% of patients who received any treatment with solri- amfetol and 63% of patients receiving placebo reported A U.S. Marine Corps F-35B Lightning II lands aboard USS Tripoli (LHA 7), April 6, 2026. Operations against Iran can exceed 34 hours, causing severe fatigue that increases risks of in-flight errors and reduced alertness. U.S. Marine Corps photo. 8 4
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