A marginal structural model to estimate the effect of antidepressant medication treatment on major cardiovascular events among people with post-traumatic stress disorder

Abstract

Background: Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model.

Methods: We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose-response relationship.

Results: People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18-1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08-1.44) and TCAs (HR 1.33, 95% CI 1.13-1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE.

Conclusions: In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose-response fashion.