Modafinil for Promoting Wakefulness in Critically Ill Patients: Current Evidence and Perspectives

Critically ill patients are predisposed to developing cognitive dysfunction, excessive daytime sleepiness (EDS), and fatigue during their stay in the intensive care unit (ICU). Modafinil, a wakefulness-promoting agent, has demonstrated potential benefits in enhancing alertness, cognitive performance, and activity levels in various clinical populations. The present narrative review aims to systematically evaluate the existing literature regarding the administration of modafinil for the treatment of EDS and fatigue in the ICU context. A comprehensive literature search was performed using the Embase, MEDLINE, Web of Science, and Google Scholar databases, covering publications up to 20 June 2025. Studies investigating the use of modafinil to improve wakefulness in ICU patients were identified. A total of nine relevant studies were included, comprising two randomized controlled trials (RCTs), two case series, and five retrospective cohort studies (n = 950 patients). Four of these studies focused on patients with traumatic brain injury or post-stroke conditions, whereas the remaining studies addressed heterogeneous ICU populations. Preliminary evidence indicates that modafinil may enhance wakefulness in selected critically ill patients and potentially facilitate their participation in rehabilitative interventions, such as physical therapy. Nonetheless, robust conclusions regarding efficacy and safety remain limited by the small sample sizes and methodological constraints of the available studies. Consequently, further large-scale RCTs are warranted to elucidate the therapeutic role of modafinil in the management of EDS and hypoactivity among ICU patients.