Risk of Psychiatric Adverse Events among Montelukast Users

ABSTRACT Background There have been conflicting results from observational studies regarding the risk of psychiatric adverse events (PAEs) with montelukast use. Objective To determine if there are associations of depressive disorders, self-harm and suicide with use of montelukast compared to inhaled corticosteroid (ICS) use. Methods Using data from the Sentinel Distributed Database (SDD) from January 1, 2000 to September 30, 2015, patients (n=457,377) exposed to montelukast or ICS, aged 6 years and older with a diagnosis of asthma, were matched 1:1 on propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for each study outcome overall and by age, sex, psychiatric history, and pre-/post-2008 labeling updates using Cox proportional hazards regression models. Results Exposure to montelukast was associated with a lower risk of treated outpatient depressive disorder (HR: 0.91; CI: 0.89-0.93). No increased risks of inpatient depressive disorder (HR: 1.06; CI: 0.90-1.24), self-harm (HR: 0.92; CI: 0.69-1.21) or self-harm using a modified algorithm (HR: 0.81; CI: 0.63-1.05) were observed with montelukast use compared to ICS use. Most PAEs occurred in the roughly one-third of patients having a past psychiatric history. Conclusion When compared to use of ICS, we did not find associations between montelukast use and hospitalizations for depression or self-harm events. Our findings should be interpreted considering the study’s limitations. Psychiatric comorbidity was common, and the majority of PAEs occurred in patients with a past psychiatric history.