Montelukast and risk for antidepressant treatment failure

Objective: While implicated in causing depression, no studies have examined the impact of montelukast on an-tidepressant effectiveness. We examined whether existing montelukast therapy was associated with acute anti-depressant treatment failure (objective 1), and whether montelukast initiation was associated with depression relapse during maintenance antidepressant therapy (objective 2), relative to inhaled corticosteroid (ICS).Methods: Patients with asthma and depression were identified using national Veterans Health Administration data from 2007 to 2019. Objective 1: 12,109 patients initiated an antidepressant after receiving montelukast or ICS for 6 months. The primary outcome was acute antidepressant treatment failure, defined as subsequent initiation of a new antidepressant or augmenting agent within 6 months. Objective 2: 14,673 patients initiated montelukast or ICS after receiving stable antidepressant monotherapy for 6 months. The primary outcome of depression relapse was defined by a subsequent change in the pre-existing maintenance antidepressant regimen within 6 months. Both objectives employed a retrospective cohort design with log-binomial regression.Results: Objective 1: Acute antidepressant failure was observed in 21.3% (628/2943) and 22.3% (2044/9166) of patients receiving montelukast versus ICS, respectively. Relative risk in adjusted analyses was 0.98 (95% CI: 0.90, 1.07). Objective 2: Depression relapse was observed in 24.4% (288/1182) and 22.4% (3027/13,491) of patients initiating montelukast versus ICS, respectively. Relative risk in adjusted analyses was 1.08 (95% CI: 0.96, 1.20) within 6 months and 1.50 (95% CI: 1.16, 1.93) within 45 days.Conclusion: Discontinuation of existing montelukast therapy is unnecessary when initiating antidepressants. However, potential evidence for depression relapse following montelukast initiation warrants additional investigation.