Comparative Risk of Neuropsychiatric Adverse Events Associated With Leukotriene-Receptor Antagonists Versus Inhaled Corticosteroids

Background: Leukotriene-receptor antagonists (LTRA) and inhaled corticosteroids (ICS) are common controller medications for asthma, but limited studies examine their comparative risks on neuropsychiatric adverse events (NAEs) in patients with asthma. Objective: To investigate the comparative risks of LTRA versus ICS on 7 distinct categories of NAEs in patients with asthma at a nationwide level. Methods: We conducted a nationwide cohort study during 2010-2021. Incident NAEs and their clinical subgroups (eg, psychotic disorders, anxiety disorders, movement disorders, behavioral and emotional disorders, mood disorders, sleep-related disorders, and personality disorders) were assessed. Cox proportional hazards regressions were used to quantify the comparative risks. Results: There were 1,249,897 patients with asthma aged 6 to 64 years. Incidence rates for NAEs were 25.10 per 1000 person-years among patients treated with LTRA and 23.46 per 1000 person-years among those treated with ICS. The incidence rate difference was 1.64 (95% confidence interval [CI]: 0.30-2.98) per 1000 person-years. Positive associations of NAEs and 3 clinical subgroups were found in patients treated with LTRA compared with ICS (hazard ratios [HR]: 1.06 [95% CI: 1.00-1.12] for NAEs; HR: 1.88 [95% CI: 1.24-2.84] for psychotic disorders; HR: 1.10 [95% CI: 1.01-1.20] for anxiety disorders; and HR: 1.27 [95% CI: 1.02-1.58] for behavioral and emotional disorders), but not for movement disorders, mood disorders, sleep-related disorders, and personality disorders. Conclusions: This nationwide cohort study identified heightened risks, ranging from 6% to 88%, of NAEs and 3 clinical subgroups in patients with asthma treated with LTRA compared with ICS. These findings underscore the necessity for clinicians to communicate with patients regarding potential neuropsychiatric harms when prescribing LTRA.