No decline in sudden cardiac death rates among younger antidepressant users

Background

Psychiatric disorders and cumulative antidepressant exposure have both been associated with an increased risk of sudden cardiac death (SCD), a relationship previously observed across age groups from 18 to 90 years. Although prior studies have identified elevated risk among prevalent antidepressant users, there is a knowledge gap regarding whether this association persists among new antidepressant users.

Purpose

To investigate the temporal trend and association between novel antidepressant use and SCD in patients aged 18-49 years in the Danish population by reviewing all available data regarding health records, SCD, & prescription redemption during the years 2007-2019.

Method

We included all Danish residents aged 18-49 years (2007-2019) without antidepressant use in the prior 3 years (n=3 551 940: 29 101 405 person-years). Using time-varying exposure based on prescription redemptions of antidepressant drug (30-day coverage), individuals were classified as current, recent (within 2 years), remote (>2 years), or never users. SCD cases were adjudicated by 2 independent physicians in the Danish SCD in the young registry . The study period was divided into three intervals (2007-2010, 2011-2014, 2015-2019) to assess temporal trends. Sudden cardiac death (SCD) risk was estimated using Cox proportional hazards models with time-varying covariates, adjusted for comorbidities.

Results

Out of 3.5 million residents, there were a total of 19 370 deaths, and 1894 cases of SCD. 484 995 were antidepressant users with 395 cases of SCD. Baseline characteristics showed that the users had more comorbidities than the never users (Table 1). Incidence rates were consistently higher among current users versus never-users across all periods (Figure 1). Incidence declined significantly among never-users (-6.63% per year; 95%CI: -8.00% to -5.25%; p= <0.001) but remained stable among current users (increased 0.79% per year; 95%CI: -3.75% to 5.54%; p= 0.74).

Adjusted hazard ratios demonstrated elevated SCD rate for current users (HR 1.20; 95%CI: 1.04-1.44; p=0.02), recent users (HR 1.40; 95%CI: 1.12-1.73; p=0.002), and borderline significance for remote users (HR 1.20; 95%CI: 1.00-1.45; p=0.051).

Conclusion

Among adults aged 18-49 years, current and recent antidepressant use was associated with increased SCD risk that remained consistently elevated across all three time periods, whereas the incidence of SCD declined among never-users. The non-declining trend among exposed individuals suggests antidepressant use may serve as a marker of persistent cardiovascular vulnerability.Figure 1.Table 1.