Residual excessive daytime sleepiness (EDS) may be seen in patients with obstructive sleep apnea (OSA) despite compliance with continuous positive airway pressure (CPAP) therapy. Residual EDS can be detrimental as it may impact cognitive performance and quality of life (QOL); hence, it should be evaluated to exclude other causes of EDS, such as hypothyroidism, narcolepsy and idiopathic hypersomnia. Once these have been ruled out, pharmacotherapy should be initiated. Various wake-promoting agents are currently available, such as modafinil/armodafinil, solriamfetol and pitolisant. This review provides updated evidence of currently available pharmacotherapy for EDS and the order of selection of various drugs. Pitolisant and solriamfetol were found to have similar efficacy. However, pitolisant has a better safety profile and should be considered as the first choice, especially in patients with cardiac comorbidities. Modafinil and armodafinil, although more economical, are less efficacious.
