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.