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The association of antihypertensive use and depressive symptoms in a large older population with hypertension living in Australia and the United States: a cross-sectional study


Cardiovascular drugs impact many pathways involved in depression pathophysiology and treatment. However, their distinct impact on mood is underrecognized and the literature is conflicting. Therefore, using a very large and well-characterised sample of older adults with hypertension, we aimed to investigate the prevalence of depressive symptoms in users of different antihypertensive classes. We analysed baseline data from 14,195 older individuals with hypertension enroled in a large clinical trial. Median age was 75 years. The association of antihypertensive use by class and depression prevalence, as measured by a validated depression scale, was determined using logistic regression models. Multivariable logistic models were implemented to account for important confounding factors. Our analyses showed a positive association between depressive symptoms and the use of beta blockers (BB) (OR: 1.37; 95% CI: 1.17–1.60, p < 0.01), compared with users of other antihypertensive classes. All other classes of antihypertensives (including angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium channel blockers) were not significantly associated with depressive symptoms. In secondary analysis, this relationship was stronger for lipophilic (39%) and nonselective BB (52%) compared with hydrophilic (26%) and selective medications (31%), respectively. This study adds further evidence for a probable association between BB and depression in a large sample of older adults with hypertension and no history of cardiovascular disease or heart failure. These findings should regenerate interest and increase awareness of clinicians about the possible adverse effects of these medications in an otherwise healthy older population.

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The authors acknowledge the efforts of research personnel and long-term involvement of participants of the ASPREE Study.


The study is supported by the National Institute on Aging and the National Cancer Institute at the National Institutes of Health (grant number U01AG029824); the National Health and Medical Research Council of Australia (grant numbers 334047 and 1127060); Monash University (Australia); the Victorian Cancer Agency (Australia). MB is supported by a NHMRC Senior Principal Research Fellowship (APP1059660 and APP1156072) and CMR is supported by a NHMRC Senior Research Fellowship (APP1045862).

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Correspondence to Bruno Agustini.

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Supplement Table 1: Examining association between the use of antihypertensive drugs and depressive symptoms (CES-D ≥8) using non-medicated (or diuretic monotherapy) as controls:


Supplement Table 2: Combination therapies and their association with depressive symptoms in multivariate model with users of other classes and non-medicated as controls (n = 14,195) *

Supplement Table 3 – Number of medication users by class and individual compounds:

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Agustini, B., Mohebbi, M., Woods, R.L. et al. The association of antihypertensive use and depressive symptoms in a large older population with hypertension living in Australia and the United States: a cross-sectional study. J Hum Hypertens 34, 787–794 (2020).

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