Antidepressant medication and risk of cardiovascular disease in posttraumatic stress disorder patients: application of marginal structural models in Korean National Health Insurance Database

Abstract

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): - National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT Introduction Previous evidence on antidepressant medication and cardiovascular disease (CVD) in posttraumatic stress disorder (PTSD) patients is mixed. We evaluated associations between antidepressant medication and CVD by applying marginal structural model. Methods We gathered medical utilization records of 27,170 patients diagnosed with PTSD in years 2004 - 2018 without prior CVD diagnosis from Korean National Health Insurance Database (NHID). PTSD and CVD were characterized in correspondence of ICD-10 diagnostic codes. We acquired information on antidepressant use from medical utilization records and categorized by medication category: selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs). Discrete-time survival analysis with marginal structural inverse probability weighting was used to test association between antidepressants and CVDs and were compared to results from traditional time-fixed model and simple time-varying model. We calculated cumulative daily defined doses (DDDs) of each antidepressant categories and conducted polynomial splining to test dose response. Results SSRI use was associated with acute coronary syndrome (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.26 - 1.86) and ischemic stroke (HR 1.33, 95% CI 1.08 - 1.63). SNRI use was associated with acute coronary syndrome (HR 1.52, 95% CI 1.09 - 2.12). TCA use was associated with acute coronary syndrome (HR 1.54, 1.21 - 1.96) and ischemic stroke (HR 1.34, 1.06 - 1.70). Polynomial spline showed positive dose-response in association between antidepressant use and CVD. Conclusion Antidepressant use is causally associated with CVD in patients with PTSD. Higher cumulative DDD of antidepressant increases the risk of CVD.