Association Between Leukotriene-Modifying Agents and Suicide in Patients with Asthma

The United States Food and Drug Administration has issued safety alerts regarding the potential for leukotriene-modifying agents (LTMAs) to cause suicide. The null hypothesis of this dissertation was that there is no association between LTMAs and suicide. Three studies were conducted to test this. First, an ecologic study was conducted that combined spontaneous reports of completed suicide with data on prescriptions dispensed for LTMAs. The rate of completed suicides per million prescriptions was calculated, and Empirical Bayes rate multipliers were determined using a mixed-effects Poisson regression analysis. Selective serotonin-reuptake inhibitors (SSRIs) and short-acting beta-agonist (SABAs) were analyzed for comparison purposes. Montelukast was associated with a significantly lower rate of suicide when compared to SSRIs, and a significantly higher rate when compared to SABAs. Second, an ecologic study was conducted that examined counts of suicide deaths by county in the United States and prescriptions dispensed. A mixed-effects Poisson regression analysis at the county-level was conducted. A negative within-county association between the rate of total LTMA prescriptions dispensed and the suicide rate by county (P = 0.0296) was found. Last, a nested case-control study was conducted using insurance claims data. Cases and controls were from a cohort of asthmatics age 5-24 years. Cases were those with a suicide attempt occurring after exposure to asthma medication. Controls were individuals at risk and were selected by incidence density sampling in a 10:1 match. Conditional logistic regression was used to determine the association between LTMA exposure and risk of attempted suicide adjusted for important covariates. Current use of any LTMA was associated with reduced risk of suicide attempt (OR 0.70, 95% CI 0.36-1.39). An elevated risk (OR 5.64, 95% CI 0.87-36.66) was observed in those 19-24 years of age, and a reduced risk in those with concomitant allergic rhinitis (OR 0.26, 95% CI 0.02-3.27). The overall conclusion from this body of work is that LTMAs are not associated with suicide. This finding was generally consistent across the three studies that were conducted.