Background: It has been suggested that venlafaxine, an antidepressant that inhibits reuptake of norepinephrine and serotonin, may increase the risk of serious cardiac arrhythmias, but no clinical study has been performed to test this hypothesis.
Objectives: To evaluate the risk of sudden cardiac death (SCD) associated with use of venlafaxine (V) compared to use of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (F), paroxetine (P), or citalopram (C).
Methods: We performed a case-control study among adults enrolled in the Kaiser Permanente (N. California) health system who were diagnosed with depression or anxiety and who filled 1 prescription for V, F, P or C from 1995–2004. Cases were patients who (1) died out-of-hospital from acute myocardial infarction, ventricular arrhythmia, or coronary artery disease or (2) presented to a hospital with a life-threatening ventricular arrhythmia then either died or were resuscitated. Cases were found through review of death certificates and automated diagnosis records. We selected up to 20 controls per case, matched on age, sex, and calendar time. We used automated prescription data to determine drug exposure on the index date. The analysis compared current use of V to current use of the other study drugs. We used conditional logistic regression to calculate odds ratios, adjusting for coronary artery disease, congestive heart failure, psychiatric co-morbidity, and other diagnoses and drugs suspected to be associated with SCD.
Results: From the 319,525 patients who met study entry criteria, we identified 598 cases of SCD (86% fatal, mean age 73 y, 53% female) and 11,827 controls. During 454,117 person- years (PY) of exposure to any study drug, the incidence rate of SCD was 1.3 (95% CI 1.2–1.4) per 1000 PY. Use of V was not associated with SCD: for V compared to F, P, or C the crude OR was 1.03 (95% CI 0.69, 1.53); the adjusted OR was 1.11 (95% CI 0.72, 1.73). Pairwise comparisons of V versus each of the comparators yielded similar results.
Conclusions: In a large population of patients with depression or anxiety prescribed venlafaxine or SSRIs, venlafaxine use was not associated with an increased risk of sudden cardiac death.
