Drug Interactions With Excessive Daytime Sleepiness Treatments

Objective: To evaluate the potential for drug interactions with pharmacotherapy for central hypersomnolence (modafinil, armodafinil, solriamfetol, pitolisant, sodium oxybate, methylphenidate, amphetamine, lithium, clarithromycin). Data Sources: A systemic literature search (1980 to June 2025) was performed using PUBMED, SCOPUS, and EMBASE to locate relevant articles. The MeSH terms included specific medication and "drug interactions." DAILYMED was used for product-specific interactions. Study Selection and Data Extraction: The search was conducted to identify drug interactions with excessive daytime sleepiness treatments. The search was limited to those articles studying humans and publications using the English language. Case reports, clinical trials, review articles, treatment guidelines, and package labeling were selected for inclusion. Data Synthesis: Primary literature and package labeling indicate that pharmacotherapy for central hypersomnolence is subject to both pharmacokinetic and pharmacodynamic interactions. While some interactions can be clinically significant, much of the data available for potential drug interactions was found in the package labeling and not from the primary literature. Conclusions: Available literature indicates that pharmacotherapy for central hypersomnolence is associated with clinically significant drug interventions and subsequent possible adverse reactions. Clinicians in all practice settings should be mindful of the potential to minimize drug interactions and optimize pharmacotherapy for hypersomnolence.