Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Abstract

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. World Health Organization. Depression and other common mental disorders: global health estimates. Geneva World Heal Organ. 2017;1–24. http://apps.who.int/iris/bitstream/10665/254610/1/WHO-MSD-MER-2017.2-eng.pdf.

  2. Pimenta E, Oparil S. Management of hypertension in the elderly. Nat Rev Cardiol. 2012;9:286–96. https://doi.org/10.1038/nrcardio.2012.27.

    Article  CAS  PubMed  Google Scholar 

  3. Chen L, Li Y, Chen P, Hu Y, Li Z. Prevalence of depression in patients with hypertension. Medicine. 2015;94:e1317.

    Article  Google Scholar 

  4. Qato DM, Ozenberger K, Olfson M. Prevalence of prescription medications with depression as a potential adverse effect among adults in the United States. JAMA. 2018;319:2289. https://doi.org/10.1001/jama.2018.6741.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Amare AT, Schubert KO, Klingler-Hoffmann M, Cohen-Woods S, Baune BT. The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies. Transl Psychiatry. 2017;7:e1007–12. https://doi.org/10.1038/tp.2016.261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Vian J, Pereira C, Chavarria V, Köhler C, Stubbs B, Quevedo J, et al. The renin-angiotensin system: a possible new target for depression. BMC Med. 2017;15:1–13.

    Article  Google Scholar 

  7. Brownstein DJ, Salagre E, Köhler C, Stubbs B, Vian J, Pereira C, et al. Blockade of the angiotensin system improves mental health domain of quality of life: A meta-analysis of randomized clinical trials. Aust NZ J Psychiatry. 2018;52:24–38.

    Article  Google Scholar 

  8. Wilson DL, Ried LD. Identifying iatrogenic depression using confirmatory factor analysis of the Center for Epidemiologic Studies Depression Scale in patients prescribed a verapamil-sustained-release-led or atenolol-led hypertension treatment strategy. Res Soc Adm Pharm. 2012;8:309–20. https://doi.org/10.1016/j.sapharm.2011.08.002.

    Article  Google Scholar 

  9. Grimm R, McNeil JJ, Applegate W, Beilin L, Espinoza S, Johnston CI, et al. Study design of ASPirin in Reducing Events in the Elderly (ASPREE): a randomized, controlled trial. Contemp Clin Trials. 2013;36:555–64. https://doi.org/10.1016/j.cct.2013.09.014.

    Article  Google Scholar 

  10. Andresen EM, Malmgren JA, Carter WB, Patrick DL. Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med. 1993;10:77–84. http://www.ncbi.nlm.nih.gov/pubmed/8037935.

    Article  Google Scholar 

  11. Mohebbi M, Nguyen V, McNeil JJ, Woods RL, Nelson MR, Shah RC, et al. Psychometric properties of a short form of the Center for Epidemiologic Studies Depression (CES-D-10) scale for screening depressive symptoms in healthy community dwelling older adults. Gen Hosp Psychiatry. 2017;1–9. https://doi.org/10.1016/j.genhosppsych.2017.08.002.

  12. Irwin M, Artin KH, Oxman M. Screening for depression in the older adult. Arch Intern Med. 1999;159:1701–4.

    Article  CAS  Google Scholar 

  13. Da Silva SA, Scazufca M, Menezes PR. Population impact of depression on functional disability in elderly: results from “são Paulo Ageing & Health Study” (SPAH). Eur Arch Psychiatry Clin Neurosci. 2013;263:153–8.

    Article  Google Scholar 

  14. Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx BW. Differential mortality rates in major and subthreshold depression: meta-analysis of studies that measured both. Br J Psychiatry. 2013;202:22–7.

    Article  Google Scholar 

  15. Mohebbi, M, Agustini, B, Woods, RL, McNeil, JJ, Nelson, MR, Shah, RC, et al. Prevalence of depressive symptoms and its associated factors among healthy community‐dwelling older adults living in Australia and the United States. International journal of geriatric psychiatry, 2019;34:1208-16.

  16. Miszkurka M, Zunzunegui MV, Ylli A, Deshpande N, Guralnik J, Phillips SP. Clinically relevant depression in old age: an international study with populations from Canada, Latin America and Eastern Europe. Psychiatry Res. 2016;241:236–41. https://doi.org/10.1016/j.psychres.2016.04.096.

    Article  PubMed  Google Scholar 

  17. Persoskie Alexander, Ferrer RA. A most odd ratio: interpreting and describing odds ratios. Am J Prev Med. 2017;52:224–8.

    Article  Google Scholar 

  18. Poirier L, Tobe SW. Contemporary use of β-blockers: clinical relevance of subclassification. Can J Cardiol. 2014;30:9–15.

    Article  Google Scholar 

  19. Battes LC, Regar E, Al Amri I, de Jaegere PPT, Pedersen SS, Oemrawsingh RM, et al. Beta blocker therapy is associated with reduced depressive symptoms 12 months post percutaneous coronary intervention. J Affect Disord. 2011;136:751–7. https://doi.org/10.1016/j.jad.2011.09.047.

    Article  CAS  PubMed  Google Scholar 

  20. Hoogwegt MT, Kupper N, Theuns DAMJ, Jordaens L, Pedersen SS. Beta-blocker therapy is not associated with symptoms of depression and anxiety in patients receiving an implantable cardioverterdefibrillator. Europace. 2012;14:74–80.

    Article  Google Scholar 

  21. Gerstman BB, Heidi MJ, Mark B, Pyone C, James ML, Richard P. The incidence of depression in new users of beta-blockers and selected antihypertensives. J Clin Epidemiol. 1996;49:809–15.http://linkinghub.elsevier.com/retrieve/pii/0895435696000170?showall=true.

    Article  CAS  Google Scholar 

  22. Ko, DT, Hebert, PR, Coffey, CS, Sedrakyan, A, Curtis, JP and Krumholz, HM. β-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. Jama, 2002;288:351–7.

    Article  CAS  Google Scholar 

  23. Johansen A, Holmen J, Stewart R, Bjerkeset O. Anxiety and depression symptoms in arterial hypertension: the influence of antihypertensive treatment. The HUNT study, Norway. Eur J Epidemiol. 2012;27:63–72.

    Article  CAS  Google Scholar 

  24. Ranchord AM, Spertus JA, Buchanan DM, Gosch KL, Chan PS. Initiation of β-blocker therapy and depression after acute myocardial infarction. Am Heart J. 2016;174:37–42. https://doi.org/10.1016/j.ahj.2015.11.018.

    Article  CAS  PubMed  Google Scholar 

  25. Verbeek DEP, Van Riezen J, De Boer RA, Van Melle JP, De Jonge P. A review on the putative association between beta-blockers and depression. Heart Fail Clin. 2011;7:89–99. https://doi.org/10.1016/j.hfc.2010.08.006.

    Article  PubMed  Google Scholar 

  26. Ringoir, L, Pedersen, SS, Widdershoven, JW, Pouwer, F, Keyzer, JM, Romeijnders, AC et al. Beta-blockers and depression in elderly hypertension patients in primary care. Family Medicine, 2014;46:447–53.

    PubMed  Google Scholar 

  27. Luijendijk HJ, Van Den Berg JF, Hofman A, Tiemeier H, Stricker BHC. β-Blockers and the risk of incident depression in the elderly. J Clin Psychopharmacol. 2011;31:45–50.

    Article  CAS  Google Scholar 

  28. Stoschitzky K, Sakotnik A, Lercher P, Zweiker R, Maier R, Liebmann P, et al. Influence of beta-blockers on melatonin release. Eur J Clin Pharmacol. 1999;55:111–5.

    Article  CAS  Google Scholar 

  29. Tahara, Y, Takatsu, Y, Shiraishi, T, Kikuchi, Y, Yamazaki, M, Motohashi, H, et al. Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation. npj Aging and Mechanisms of Disease, 3;2017:1–11.

  30. Leentjens AFG. Neurobiological correlates of emotional processing in Parkinson’s disease: a systematic review of experimental studies. J Psychosom Res. 2017;100:65–76. https://doi.org/10.1016/j.jpsychores.2017.07.009.

    Article  PubMed  Google Scholar 

  31. Harrell CS, Gillespie CF, Neigh GN. Energetic stress: the reciprocal relationship between energy availability and the stress response. Physiol Behav. 2016;166:43–55. https://doi.org/10.1016/j.physbeh.2015.10.009.

    Article  CAS  PubMed  Google Scholar 

  32. McCallum L, Boal AH, Muir S, Touyz RM, Smith DJ, Dominiczak AF, et al. Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders. Hypertension.2016;68:1132–8.

    Article  Google Scholar 

  33. Nasr SJ, Crayton JW, Agarwal B, Wendt B, Kora R. Lower frequency of antidepressant use in patients on renin-angiotensin-aldosterone system modifying medications. Cell Mol Neurobiol. 2011;31:615–8.

    Article  Google Scholar 

  34. Lionakis N, Mendrinos D, Sanidas E, Favatas G, Georgopoulou M. Hypertension in the elderly. World J Cardiol. 2012;26:135–47.

    Article  Google Scholar 

  35. Ntourakis D, Agouridis AP, Johnson EO, Tsioutis C, Yiallouris A, Agapidaki E, et al. Adrenal aging and its implications on stress responsiveness in humans. Front Endocrinol. 2019;10:1–12.

    Article  Google Scholar 

  36. Tully, PJ, Peters, R, Pérès, K, Anstey, KJ and Tzourio, C. Effect of SSRI and calcium channel blockers on depression symptoms and cognitive function in elderly persons treated for hypertension: three city cohort study. International psychogeriatrics, 2018;30:1345–54.

  37. Atkinson, LZ, Colbourne, L, Smith, A, Harmer, CH, Nobre, AC, Rendell, J, et al. The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS): study protocol for a randomised controlled, experimental medicine study. Trials, 2019;20; p.120.

  38. Agustini, B. and Berk, M. Medications with depression as an adverse effect. Jama, 2018;320:1815.

  39. Bangalore S, Sawhney S, Messerli FH. Relation of beta-blocker-induced heart rate lowering and cardioprotection in hypertension. J Am Coll Cardiol. 2008;52:1482–9.

    Article  CAS  Google Scholar 

  40. Parekh N, Page A, Ali K, Davies K, Rajkumar C. A practical approach to the pharmacological management of hypertension in older people. Ther Adv Drug Saf. 2017;8:117–32.

    Article  Google Scholar 

  41. Lindholm LH, Carlberg B, Samuelsson O. Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366:1545–53.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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

Funding

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).

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to Bruno Agustini.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

41371_2020_303_MOESM1_ESM.docx

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:

41371_2020_303_MOESM2_ESM.docx

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:

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1038/s41371-020-0303-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41371-020-0303-y

This article is cited by

Search

Quick links