Long-term antidepressant treatment for ≥6 years was associated with an increased risk of sudden cardiac death (HR 1.74; 95% CI 1.59-1.90), with current users showing the highest risk.
Cohort (n=4,300,000)
Does the cumulative duration and recency of antidepressant treatment increase the risk of sudden cardiac death in adults?
Long-term and current antidepressant use is associated with a duration- and recency-dependent increased risk of sudden cardiac death across major drug classes.
Effect estimate: HR 1.74 (95% CI 1.59-1.90)
BACKGROUND AND AIMS Antidepressants are among the most widely prescribed medications worldwide. While prior studies suggest associations between antidepressant use and adverse cardiovascular outcomes, the impact of treatment duration and recency on sudden cardiac death (SCD) risk remains unclear, limiting clinical risk stratification. OBJECTIVE To investigate whether cumulative duration and recency of antidepressant treatment are associated with SCD risk, and whether associations differ across drug classes. METHODS We conducted a nationwide cohort study of 4.3 million Danish residents aged 18-90 years during 2010. Antidepressant exposure was ascertained from the national prescription registry (1999-2009). Deaths were adjudicated as SCD or non-SCD. Multivariable Cox models estimated hazard ratios (HRs). Antidepressant use was defined as ≥2 prescriptions within one calendar year and categorized by cumulative duration (1-5 years vs ≥6 years) and recency (remote, recent, or current). RESULTS Among 6002 SCDs, 1907 (32%) occurred in antidepressant users. Adjusted HRs were 1.41 (95% CI 1.31-1.51) for 1-5 years and 1.74 (95% CI 1.59-1.90) for ≥6 years of use. A temporal gradient emerged: current users showed highest risk (HR 1.71, 95% CI 1.59-1.83) versus recent (HR 1.24, 95% CI 1.09-1.42) and remote (HR 1.11, 95% CI 0.97-1.27) users. Associations were consistent across drug classes: Selective Serotonin Receptor Inhibitors (SSRI) HR 1.38 (95% CI:1.28-1.49) and 1.57(95% CI:1.42-1.75) and Tricyclic Antidepressants(TCA) 1.24 (95% Cl:1.09-1.42) and 1.40 (95% CI:1.15-1.71) for 1-5 and ≥6 years respectively. CONCLUSION Long-term antidepressant treatment was associated with increased SCD risk in a duration- and recency-dependent manner across major drug classes. While causality cannot be inferred, these findings identify patients receiving prolonged antidepressant therapy as a population at elevated cardiovascular risk warranting further investigation.
Mujkanovic et al. (Sun,) conducted a cohort in Sudden cardiac death (n=4,300,000). Antidepressants vs. Non-users was evaluated on Sudden cardiac death (HR 1.74, 95% CI 1.59-1.90). Long-term antidepressant treatment for ≥6 years was associated with an increased risk of sudden cardiac death (HR 1.74; 95% CI 1.59-1.90), with current users showing the highest risk.