Leukotriene receptor antagonists (LTRAs) were approved by the U.S. Food and Drug Administration (FDA) in the late 1990s for the prophylaxis and chronic treatment of asthma (Kelloway, 1997; Markham and Faulds, 1998). Asthma, a chronic inflammatory airway disease, impacts over 300 million individuals globally, imposing significant social and economic burdens. (Loftus and Wise, 2015; Pijnenburg and Fleming, 2020; Stern et al., 2020). LTRAs, which work by preventing the inflammatory effects of the leukotrienes, are recommended as first-line treatment in asthma treatment guidelines along with the combination of inhaled corticosteroids and long-acting beta2 agonists (Cloutier et al., 2020). LTRAs are also utilized for the treatment of diseases outside the approved indications. For instance, LTRAs are used to prevent capsular contracture after breast augmentation (Sapountzis et al., 2012), treat atopic dermatitis (Chin and Lee, 2018), and address periosteal contracture (Huang and Handel, 2010).

Although LTRAs, including montelukast, zafirlukast, and zileuton, etc. are generally well-tolerated, post-marketing surveillance has reported serious neuropsychiatric adverse events (AEs) such as depression, anxiety, and agitation. (Bian et al., 2021; Clarridge et al., 2021). In response to pharmacovigilance data, the FDA mandated a precautionary measure in the product labeling of LTRAs to depict the range of reported neuropsychiatric events (NEs) (Clarridge et al., 2021). However, observational studies have reported conflicting results (Dixon et al., 2021; Glockler-Lauf et al., 2019; Schumock et al., 2012). Much of the evidence is based on pediatric and adolescent populations, and relatively little is known about the potential adverse outcome among adults (Law et al., 2018). In this cross-sectional study, we aimed to explore whether there are associations of depression with use of LTRAs in adults using data from the National Health and Nutrition Examination Survey (NHANES).