Distinct effects of antihypertensives on depression in the real-world setting: A retrospective cohort study

Background: Evidence is increasing that pathways of antihypertensives may have a role in the pathogenesis of depression. However, how the class of antihypertensives affects depression risk remains unclear. Methods: The effects of different classes of antihypertensives on depression were explored using an insurance database in Beijing, China. Antihypertensives in our study included calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), and diuretics (DIUs). Those initially treated with only one class of antihypertensives were included. Stratified analysis was conducted for demographic characteristics, comorbidities, and statin prescriptions. Results: In total, 181,709 newly detected hypertension patients were included. The median follow-up period was 4.33 years and 19,030 participants were with depression by the end. After adjusting for covariates, the incidence density (95% confidence interval, CI) of depression in the BB, ACEI, DIU, CCB, and ARB groups was 3.16 (2.98-3.33), 3.10 (2.91-3.29), 2.70 (2.45-2.94), 2.67 (2.53-2.81), and 2.30 (2.16-2.43) per 100 person-years, respectively. Compared with ARB group, the hazard ratio (95% CI) of depression for BB, ACEI, DIU, and CCB group was 1.37 (1.32-1.43), 1.35 (1.28-1.42), 1.17 (1.08-1.27), and 1.16 (1.12-1.21), respectively. Stratified analysis suggested the highest depression ID remained within the BB or ACEI group. Limitations: Detailed clinical information was unavailable, which may introduce bias. Patients on monotherapy as initial treatment were included and caution is needed for extrapolation. Conclusions: Compared with ARBs, there may be a class effect of other antihypertensives on the risk of depression.