Montelukast and risk for antidepressant treatment failure

• Published in: Journal of psychosomatic research 2023-01, Vol.164, p.111075, Article 111075
• Main Authors: Chung, Haemy, Hanken, Kaitlin, Gerke, Alicia K., Lund, Brian C.
• Format: Article
• Language: English
• Subjects: Acetates - adverse effects; Anti-Asthmatic Agents - adverse effects; Antidepressant drugs; Antidepressive Agents - adverse effects; Asthma; Depressive disorder; Humans; Montelukast; Quinolines - adverse effects; Retrospective Studies; Treatment Failure; Treatment Outcome
• ISSN: 0022-3999; 1879-1360; 1879-1360
• DOI: 10.1016/j.jpsychores.2022.111075

While implicated in causing depression, no studies have examined the impact of montelukast on antidepressant effectiveness. We examined whether existing montelukast therapy was associated with acute antidepressant treatment failure (objective 1), and whether montelukast initiation was associated with depression relapse during maintenance antidepressant therapy (objective 2), relative to inhaled corticosteroid (ICS). 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. 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. Discontinuation of existing montelukast therapy is unnecessary when initiating antidepressants. However, potential evidence for depression relapse following montelukast initiation warrants additional investigation. •Montelukast prescribing information warns of risk for neuropsychiatric events.•Unknown whether montelukast adversely impacts response to antidepressants.•Montelukast was not associated with acute antidepressant treatment failure.•Some evidence for depression relapse when starting montelukast.•Relapse risk greatest during first 1–3 months following montelukast initiation.