Risk of Self-Harm and the Use of Leukotriene Receptor Antagonists and Inhaled Corticosteroids: a Population-Based Study

Abstract

Background: Whether leukotriene receptor antagonist (LTRA) or inhaled corticosteroid (ICS) use can increase the risk of self-harm remains unclear. Objective: To evaluate the association between self-harm and use of LTRAs and ICSs among patients with asthma. Methods: This self-controlled case series study used data from the UK Clinical Practice Research Datalink linked to hospital and mortality records. We included patients with asthma aged 10 years or more who had at least 1 prescription of LTRA, 1 prescription of ICS, and an incident self-harm during the period 2005 to 2020. Incidence rate ratios (IRRs) of self-harm during periods of (presented in order of precedence if they overlapped) pre-LTRA, pre-ICS, LTRA-alone, ICS-alone, and combination use of LTRA and ICS, versus nonuse, were calculated using conditional Poisson regression model. Additional analyses using self-controlled case series extension, case-case-time-control, and cohort study designs were used to examine robustness of results. Results: Among 313,943 individuals prescribed LTRAs and ICSs, 2900 had incident self-harm. IRRs were 0.77 (95% CI, 0.58-1.01) during pre-LTRA, 0.68 (95% CI, 0.57-0.82) during LTRA-alone, and 0.70 (95% CI, 0.56-0.86) during combination use. Further analysis suggested that the self-harm incidence was lower during the first 90 days of LTRA use (IRR, 0.74; 95% CI, 0.58-0.95), before returning to nonuse level (IRR, 0.93; 95% CI, 0.74-1.17). Comparable incidence to nonuse was observed during pre-ICS (IRR, 0.99; 95% CI, 0.71-1.39) and ICS-alone (IRR, 0.88; 95% CI, 0.75-1.04). The results were robust across sensitivity analyses and study designs, which did not suggest increased risk of self-harm with LTRA/ICS use. Conclusions: Using the self-controlled case series design, which was based on comparisons within a population with both the outcome and exposure of interest, our study does not support an association between self-harm and LTRA or ICS use in patients with asthma.