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Abstract
Background:
The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA) and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings.
Methods:
We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year, and antidepressant utilization. We also assessed the intracounty and intercounty associations.
Results:
There were 249,872 suicides in the US between 1999 and 2006, and the annual suicide rate ranged from 11.17 to 11.92 per 100,000 population. There were 118.63, 11.68, and 0.12 million prescriptions dispensed for montelukast, zafirlukast, and zileuton, respectively, between 1999 and 2006. The mean rate of LTMA prescriptions dispensed by county was 42.91 (95% confidence interval [CI] 42.78–43.04), 4.82 (95% CI 4.81–4.84), and 0.05 (95% CI 0.05–0.05) per 1000 for montelukast, zafirlukast, and zileuton, respectively. We found a negative within-county association between the rate of total LTMA prescriptions dispensed and the suicide rate by county (P = 0.0296). This association was primarily driven by montelukast.
Conclusion:
Our results, while subject to certain limitations, provide preliminary evidence that the association between LTMA and suicide could be different (ie, reduced risk) than that which might be anticipated based on previous warnings. Patient-level research is needed to understand more clearly the association between LTMA and suicide.
Disclosure
No funding was received for the conduct of this study. Dr Lee has served as a consultant for Merck and has been an investigator on a grant funded in part by Astra Zeneca – both of which are manufacturers of drugs included in this study. The other authors report no conflicts of interest in this work. All persons who made substantial contributions to the work are included as authors. The statements, findings, conclusions, views, and opinions contained and expressed in this article are based in part on data obtained under license from the following IMS Health Incorporated information service(s): Xponent™, January 1999 – December 2009, IMS Health Incorporated. All Rights Reserved. Such statements, findings, conclusions, views, and opinions are not necessarily those of IMS Health Incorporated or any of its affiliated or subsidiary entities. Similarly, data from the National Center for Health Statistics as used in this analysis. All analysis, interpretations, and conclusions reached from these data are those of the authors and not the National Center for Health Statistics.