Risk of major adverse cardiovascular events in treatment-resistant or severe depression

Background: Depression is associated with higher risk of major adverse cardiovascular events (MACE). Whether patients with treatment-resistant depression (TRD) or severe depression have an even higher risk is uncertain. Methods: Patients 18-75 years old with a depressive episode in specialized psychiatric care were identified using national Swedish registers. Patients with depression were matched with population comparators, patients with TRD with non-TRD comparators, and severe depression with non-severe depression comparators. The primary outcome was MACE, including acute myocardial infarction, stroke, heart failure, and cardiovascular death. Hazard ratios were calculated, adjusting for sociodemographic and clinical covariates. Results: We identified 143,731 patients with depression, including 23,335 with TRD and 45,217 with severe depression. Patients with depression had a higher hazard of MACE vs comparators (aHR 1.50, 95%CI 1.40-1.62). Hazards of MACE were overall similar in patients with TRD vs comparators (aHR 1.06, 95%CI 0.93-1.22) and severe depression vs comparators (aHR 1.04, 95%CI 0.96-1.13). Analyzing separate outcomes, patients with TRD had a higher hazard of cardiovascular death (aHR 1.32, 95 %CI 1.03-1.69). Stratified by age, there was an elevated hazard of MACE among patients 18-29 years old with severe depression (aHR 2.82, 95%CI 1.24-6.41). Limitations: Register data lacks information on some potential confounders. Conclusions: Patients with TRD or severe depression are not at additional overall risk of MACE compared to other depressed patients. However, an additional risk may exist in younger patients with severe depression and specifically of cardiovascular death in patients with TRD.