Iessa, N;
(2013)
Detecting Suicide as an Adverse Drug Reaction: Association between Suicide and Montelukast.
Doctoral thesis , UCL (University College London).
Abstract
The hypothesised association between leukotriene receptor antagonists (LTRA) and suicide is not clear. In this thesis, causality assessments of Individual Case Safety Reports (ICSRs) and a novel pharmaco-vigilance method using electronic healthcare records (EHRs) are used to examine the strength of this hypothesis. This thesis is also the first to describe the application of the self-controlled case series (SCCS) methodology to the study of suicide and LTRA using UK primary care data. There are 5 components: 1) an initial screening of VigiBase, a global database of ICSRs for drugs associated with suicide; 2) a review of the literature for evidence of an association of suicide with montelukast; 3) an assessment of the strength of this association using causality assessments of ICSRs, and an overall causality assessment using multiple data sources in accordance to the Bradford Hill guidelines of causality; 4) Temporal-Pattern Discovery (TPD), a novel data-mining method, was applied to UK EHRs to complement signal detection; 5) an observational study using an SCCS methodology was used to examine whether LTRAs are associated with an increased risk of suicide attempts. We found montelukast to be amongst medication with the most number of global ICSRs for suicide-related adverse events in young people aged 2-17. However, causality assessment of ICSRs revealed that reports were often incomplete and did not strengthen this hypothesis. Also, complementary signal detection using the TPD method in EHRs did not detect a signal. Finally, the SCCS study using EHRs from a UK primary care database did not provide evidence to support the hypothesis; on the contrary we found the risk of suicide attempts decreased after cessation of a course of LTRAs in females (IRR=0.46 95%CI 0.22, 0.96). In conclusion, there is little evidence to support an association between suicide and montelukast, however this link cannot be excluded.
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