Stable interindividual differences in modafinil's effect on vigilance during sleep deprivation

Jeroen Van Cutsem^1,2*Martine Van Puyvelde^1,3,4Nicholas Vandenberg^1,5Emilie Dessy⁶Frederic Detaille^1,7An Van Rompay⁸Olivier Mairesse^1,9Catherine DROGOU^10,11Fabien Sauvet^10,11Xavier Neyt¹Nathalie Pattyn^1,12,5,9Guido Simonelli^12,13,5

• ¹VIPER Research Unit, Royal Military Academy (Belgium), Brussels, Belgium
• ²Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, elsene, Brussels, Belgium
• ³Experimental and Applied Psychology, Department of Psychology and Educational Sciences, Vrije Universiteit Brussel, Brussels, Belgium
• ⁴Clinical & Lifespan Psychology, Department of Psychology and Educational Sciences, Vrije Universiteit Brussel, Brussels, Belgium
• ⁵Centre d’études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montreal, Quebec, Canada
• ⁶Service Public de Wallonie, Namur, Belgium
• ⁷Aviation Safety Directorate, Belgian Defence, Belgium, Brussels, Belgium
• ⁸Queen Astrid Military Hospital, Brussels, Belgium
• ⁹Brain, Body and Cognition, Department of Psychology, Faculty of Psychology and Educational Sciences, Vrije Universiteit Brussel, Brussels, Belgium
• ¹⁰Institut de Recherche Biomédicale des Armées (IRBA), Bretigny sur Orge, France
• ¹¹EA7330 Sommeil-Vigilance-Fatigue et Santé Publique (VIFASOM), Paris, Île-de-France, France
• ¹²Département de Médecine, Faculté de Médecine, Université de Montréal, Montreal, Quebec, Canada
• ¹³Département de Neurosciences, Faculté de Médecine, Université de Montréal, Montréal, Quebec, Canada

Abstract Rationale: In specific operational contexts (i.e., military aviation), the off-label use of modafinil is officially regulated. However, safety concerns are still raised. Objectives: To study the stability and robustness of interindividual differences in modafinil sensitivity, both in terms of risks and benefits in military student pilots. Methods: Eleven healthy military student pilots (21±2 yr; 1 woman) were tested in a within-subject randomized counterbalanced crossover design to compare modafinil (2x200 mg; EXP) vs placebo (CON) effects during extended wakefulness (24hrs). Throughout both trials, participant's vital signs, mood, vigilance [i.e., Psychomotor Vigilance Task (PVT)] and self-monitoring ability were measured. Additionally, four participants were genotyped [i.e., COMT (rs4680) and PER3 (rs228697)]. We used Pearson correlation coefficients to evaluate the relationship between PVT performance and the performance self-monitoring scores. To evaluate the stability of interindividual differences in the effectiveness of modafinil to improve PVT performance and sleepiness, an intraclass correlation coefficient (ICC) was calculated for the delta score (CON-EXP) of both outcome measures. Results: Modafinil significantly improved PVT performance (p≤0.034) and sleepiness (p≤0.029) at 2AM and 4AM during the sleep deprivation night. The stability of the non-adjusted reaction time-delta score was very high (ICC=0.90). Non-adjusted reaction time only correlated with the performance self-monitoring scores in CON (r≥- 0.35; p<0.001). Conclusions: Stable interindividual differences in the effectiveness of modafinil to counteract the sleep deprivation-associated decrease in vigilance exist. Further research should focus on quantifying the extent to which modafinil-induced overconfidence and subjective rebound sleepiness actually constitute potential problems in operational environments (e.g., perhaps using war game simulations).