Asthma and lower airway disease
Risk of suicide attempt in asthmatic children and young adults prescribed leukotriene-modifying agents: A nested case-control study

https://doi.org/10.1016/j.jaci.2012.04.035Get rights and content

Background

The US Food and Drug Administration has issued safety alerts about leukotriene receptor–modifying agents and suicidality/suicide, but because these were based on case reports, there is controversy about the association.

Objective

We conducted a nested case-control study to determine the association between leukotriene-modifying agents (LTMAs) and attempted suicide among asthmatic children and young adults.

Methods

Cases and control subjects were from a cohort of asthmatic patients aged 5 to 24 years who were new users of LTMAs or other asthma medications. Data were from an insurance claims database. Cases were defined as those with a suicide attempt (SA) occurring after exposure to asthma medication. Control subjects were persons at risk and were selected by using incidence density sampling in a 10:1 match. Conditional logistic regression was used to determine the association between LTMA exposure and the risk of attempted suicide adjusted for important covariates.

Results

We identified 344 cases and 3438 matched control subjects. Cases were more likely than control subjects to have risk factors for suicide. We found that current use of any LTMA was not associated with increased risk of an SA; in fact, the direction of effect was the opposite (adjusted odd ratio, 0.70; 95% CI, 0.36-1.39).

Conclusion

In this analysis we found that use of LTMAs was not associated with an increased risk of SAs in children, adolescents, and young adults with asthma. Further research needs to be conducted to more fully understand the association between LTMAs and suicide, particularly in subpopulations.

Section snippets

Methods

We conducted a case-control study of the association between the LTMAs and attempted suicides. Cases and control subjects were nested within a cohort of asthmatic children and young adults identified in a commercial health insurance claims database who were new users of LTMAs or other asthma medications, as shown in Fig 1.

Results

Limiting the dataset based on exclusion criteria described above (as shown in Fig 2) resulted in an analytic cohort of 195,028 patients from which cases and control subjects were drawn. There were 344 cases, and all except 1 were able to be matched with 10 control subjects; 1 case was matched with 8 control subjects, for a total of 3,438 control subjects.

Demographic and clinical characteristics of the cases and control subjects are shown in Table I. Cases were more likely than control subjects

Discussion

In this nested case-control study we found no statistically significant association between use of LTMAs and SAs in the general population of patients aged 5 to 24 years. This finding is consistent with previous research on the association between LTMAs and suicide, including a retrospective review of LTMA clinical trials conducted by the FDA.8

After the FDA warning, Jick et al13 conducted a population-based cohort study to examine the potential association. The investigators identified 23,500

References (52)

  • G. Philip et al.

    The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis

    Curr Med Res Opin

    (2004)
  • Top 200 drugs for 2010 by sales. Available at: http://drugs.com/top200.html. Accessed May 11,...

  • Early communication about an ongoing safety review of montelukast (Singulair), 3/23/2009. Postmarket drug safety information for patients and providers

    (2008)

  • Follow-up to the March 27, 2008, communication about the ongoing safety review of montelukast (Singulair), 1/13/2009. Postmarket drug safety information for patients and providers

    (2009)

  • Updated information on leukotriene inhibitors: montelukast (marketed as Singulair), zafirlukast marketed as Accolate), and zileuton (marketed as Zyflo and Zyflo CR), 8/28/2009. Postmarket drug safety information for patients and providers

    (2009)
  • G.T. Schumock et al.

    Association between leukotriene-modifying agents and suicide: what is the evidence?

    Drug Saf

    (2011)
  • G.T. Schumock et al.

    The association between leukotriene-modifying agents and spontaneously reported suicide

    Drug Information J

    (2012)
  • G.T. Schumock et al.

    Relationship between leukotriene-modifying agent prescriptions dispensed and rate of suicide deaths by county in the US

    Drug Healthcare Patient Saf

    (2011)
  • H. Jick et al.

    Rate of suicide in patients taking montelukast

    Pharmacotherapy

    (2009)
  • N. Jewell

    Assessing significance in a 2 × 2 table. In: Statistics in epidemiology

    (2004)
  • P.C. Heaton et al.

    Analysis of the effectiveness and cost benefit of leukotriene modifiers in adults with asthma in the Ohio Medicaid population

    J Manag Care Pharm

    (2006)
  • W. Coryell et al.

    Clinical predictors of suicide in primary major depressive disorder

    J Clin Psychiatry

    (2005)
  • E.M. Jolin et al.

    Suicide risk factors in children and adolescents with bipolar disorder

    Curr Psychiatry Rep

    (2007)
  • B.A. Palmer et al.

    The lifetime risk of suicide in schizophrenia: a reexamination

    Arch Gen Psychiatry

    (2005)
  • C. Haw et al.

    Dementia and suicidal behavior: a review of the literature

    Int Psychogeriatr

    (2009)
  • J. Paris

    The development of impulsivity and suicidality in borderline personality disorder

    Dev Psychopathol

    (2005)

    • Cited by (0)

    Disclosure of potential conflict of interest: T. A. Lee is a consultant for Merck and Forest Pharmaceuticals and has received research support from Novartis. The rest of the authors declare they have no relevant conflicts of interest.

    View full text
    Copyright © 2012 Published by Mosby, Inc.