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.

  • Review Article
  • Published:

Association between antihypertensive drug use and the risk of depression: a systematic review and network meta-analysis

Journal of Human Hypertension volume 39, pages 246–253 (2025)Cite this article

Subjects

Abstract

Hypertension is the biggest and most prevalent risk factor for cardiovascular diseases. Depression is the most common psychiatric illness worldwide. Many studies have linked the development of new depression to the use of antihypertensive drugs. This meta-analysis was done to ascertain the relationship. Using standard reporting techniques a literature search was undertaken in Pubmed from inception till 10 May 2024. The risk bias assessment was done using the ROBINS-I tool. Data for the odds ratio were combined using Revman 5.4 using a random or fixed effects model. Our analysis found a significant association between beta blockers and calcium channel blockers use and the risk of developing new depression. Results for other classes of antihypertensives were not significant. The findings highlight the importance of taking into account the potential psychiatric side effects of antihypertensive drugs in people with hypertension. Physicians should stay vigilant and screen their patients for these conditions regularly.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Risk of Bias Table.
Fig. 3
Fig. 4: Forest plot showing the association of Angiotensin-Converting Enzyme Inhibitors/ Angiotensin II Receptor Blockers use and the odds ratio developing of depression.
Fig. 5: Forest plot showing the association of Beta-Blockers use and the odds ratio developing of depression.
Fig. 6: Forest plot showing the association of Calcium Channel Blockers use and the odds ratio developing of depression.
Fig. 7: Forest plot showing the association of Diuretics use and the odds ratio developing of depression.
Fig. 8: Forest plot showing the association of Antihypertensives use and the odds ratio developing of depression.

Similar content being viewed by others

Data availability

The search strategy can be found in Supplementary File 1. All other data can be obtained from the corresponding author upon reasonable request.

References

  1. Raič M. Depression and heart diseases: leading health problems. Psychiatr Danub. 2017;4:770–7.

    Google Scholar 

  2. Li Z, Li Y, Chen L, Chen P, Hu Y. Prevalence of depression in patients with hypertension: a systematic review and meta-analysis. Medicine. 2015;94:e1317.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9:137–50.

    Article  PubMed Central  Google Scholar 

  4. Malhi GS, Mann JJ. Depression. Lancet Lond Engl. 2018;392:2299–312.

    Article  Google Scholar 

  5. Johannessen L, Strudsholm U, Foldager L, Munk-Jørgensen P. Increased risk of hypertension in patients with bipolar disorder and patients with anxiety compared to background population and patients with schizophrenia. J Affect Disord. 2006;95:13–7.

    Article  PubMed  Google Scholar 

  6. Kretchy IA, Owusu-Daaku FT, Danquah SA. Mental health in hypertension: assessing symptoms of anxiety, depression and stress on anti-hypertensive medication adherence. Int J Ment Health Syst. 2014;8:25.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Fan B, Zhao JV. Genetic proxies for antihypertensive drugs and mental disorders: mendelian randomization study in European and East Asian populations. BMC Med. 2024;22:6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Tanase DM, Gosav EM, Radu S, Ouatu A, Rezus C, Ciocoiu M, et al. Arterial hypertension and interleukins: potential therapeutic target or future diagnostic marker? Int J Hypertens. 2019;2019:3159283.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cruickshank JM. The role of beta-blockers in the treatment of hypertension. Adv Exp Med Biol. 2017;956:149–66.

    Article  PubMed  Google Scholar 

  10. Beers MH, Passman LJ. Antihypertensive medications and depression. Drugs. 1990;40:792–9.

    Article  PubMed  CAS  Google Scholar 

  11. 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  PubMed  PubMed Central  Google Scholar 

  12. Agustini B, Mohebbi M, Woods RL, McNeil JJ, Nelson MR, Shah RC, 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. 2020;34:787–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Kessing LV, Rytgaard HC, Ekstrøm CT, Torp-Pedersen C, Berk M, Gerds TA. Antihypertensive drugs and risk of depression: a nationwide Population-Based Study. Hypertens Dallas Tex 1979. 2020;76:1263–79.

    CAS  Google Scholar 

  14. Cao YY, Xiang X, Song J, Tian YH, Wang MY, Wang XW, et al. Distinct effects of antihypertensives on depression in the real-world setting: a retrospective cohort study. J Affect Disord. 2019;259:386–91.

    Article  PubMed  CAS  Google Scholar 

  15. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.

    Article  PubMed  CAS  Google Scholar 

  17. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

    Article  PubMed  PubMed Central  Google Scholar 

  18. McGuinness LA, Higgins JPT. Risk-of-bias VISualization (robvis): An R package and Shiny web app for visualizing riskof-bias assessments. Res Syn Meth. 2021;12:55–61.

  19. Cornell JE, Mulrow CD, Localio R, Stack CB, Meibohm AR, Guallar E, et al. Random-effects meta-analysis of inconsistent effects: a time for change. Ann Intern Med. 2014;160:267–70.

    Article  PubMed  Google Scholar 

  20. Review Manager (RevMan) [Computer program]. Version 5.4. The Cochrane Collaboration, 2020

  21. Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA2020: an R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Syst Rev. 2022;18:e1230.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Zill P, Baghai TC, Schüle C, Born C, Früstück C, Büttner A, et al. DNA methylation analysis of the Angiotensin Converting Enzyme (ACE) gene in major depression. PLOS ONE. 2012;7:e40479.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Bornand D, Reinau D, Jick SS, Meier CR. β-blockers and the risk of depression: a Matched Case-Control Study. Drug Saf. 2022;45:181–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. 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.

    Article  PubMed  Google Scholar 

  25. Poirier L, Tobe SW. Contemporary use of β-blockers: clinical relevance of subclassification. Can J Cardiol. 2014;30:S9–15.

    Article  PubMed  Google Scholar 

  26. Riemer TG, Villagomez Fuentes LE, Algharably EAE, Schäfer MS, Mangelsen E, Fürtig MA, et al. Do β-blockers cause depression? Hypertension. 2021;77:1539–48.

    Article  PubMed  CAS  Google Scholar 

  27. Li Y, Fan Y, Sun Y, Alolga RN, Xiao P, Ma G. Antihypertensive drug use and the risk of depression: a systematic review and network meta-analysis. Front Pharmacol. 2021;12:777987.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Chauquet S, Zhu Z, O’Donovan MC, Walters JTR, Wray NR, Shah S. Association of antihypertensive drug target genes with psychiatric disorders: a mendelian Randomization Study. JAMA Psychiatry. 2021;78:623–31.

    Article  PubMed  Google Scholar 

  29. Du XL, Martinez J, Yamal JM, Simpson LM, Davis BR. The 18-year risk of cancer, angioedema, insomnia, depression, and erectile dysfunction in association with antihypertensive drugs: post-trial analyses from ALLHAT-Medicare linked data. Front Cardiovasc Med. 2023;10:1272385.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Lee JM, Choi S, Jeong S, Son JS, Park SJ, Chang J, et al. Distinct effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on major depressive disorder: a nationwide cohort study. Asian J Psychiatry. 2023;81:103436.

    Article  Google Scholar 

  31. Shaw RJ, Mackay D, Pell JP, Padmanabhan S, Bailey DS, Smith DJ. The relationship between antihypertensive medications and mood disorders: analysis of linked healthcare data for 1.8 million patients. Psychol Med. 2021;51:1183–91.

    Article  PubMed  Google Scholar 

  32. van Sloten TT, Souverein PC, Stehouwer CD, Driessen JH. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and risk of depression among older people with hypertension. J Psychopharmacol Oxf Engl. 2022;36:594–603.

    Article  Google Scholar 

  33. Van de Velde S, Bracke P, Levecque K. Gender differences in depression in 23 European countries. Cross-national variation in the gender gap in depression. Soc Sci Med 1982. 2010;71:305–13.

    Google Scholar 

  34. Boal AH, Smith DJ, McCallum L, Muir S, Touyz RM, Dominiczak AF, et al. Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders. Hypertens Dallas Tex 1979. 2016;68:1132–8.

    CAS  Google Scholar 

  35. Feng L, Tan CH, Merchant RA, Ng TP. Association between depressive symptoms and use of HMG-CoA reductase inhibitors (statins), corticosteroids and histamine H(2) receptor antagonists in community-dwelling older persons: cross-sectional analysis of a population-based cohort. Drugs Aging. 2008;25:795–805.

    Article  PubMed  CAS  Google Scholar 

  36. Gammoh O, Bjørk MH, Al Rob OA, AlQudah AR, Hani AB, Al-Smadi A. The association between antihypertensive medications and mental health outcomes among Syrian war refugees with stress and hypertension. J Psychosom Res. 2023;168:111200.

    Article  PubMed  Google Scholar 

  37. Gerstman BB, Jolson HM, Bauer M, Cho P, Livingston JM, Platt R. The incidence of depression in new users of beta-blockers and selected antihypertensives. J Clin Epidemiol. 1996;49:809–15.

    Article  PubMed  CAS  Google Scholar 

  38. 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  PubMed  CAS  Google Scholar 

  39. Michal M, Wiltink J, Lackner K, Wild PS, Zwiener I, Blettner M, et al. Association of hypertension with depression in the community: results from the Gutenberg Health Study. J Hypertens. 2013;31:893–9.

    Article  PubMed  CAS  Google Scholar 

  40. Ringoir L, Pedersen SS, Widdershoven JWMG, Pouwer F, Keyzer JML, Romeijnders AC, et al. Beta-blockers and depression in elderly hypertension patients in primary care. Fam Med. 2014;46:447–53.

    PubMed  Google Scholar 

  41. Simonson W, Han LF, Davidson HE. Hypertension treatment and outcomes in US nursing homes: results from the US National Nursing Home Survey. J Am Med Dir Assoc. 2011;12:44–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: Jay Tewari, Khalid Ahmad Qidwai, Ajoy Tewari.

Authors and Affiliations

  1. Department of Internal Medicine, King George’s Medical University, Lucknow, India

    Jay Tewari, Khalid Ahmad Qidwai, Anadika Rana & Vanshika Singh

  2. Department of Internal Medicine, HIND Institute of Medical Sciences, Barabanki, India

    Ajoy Tewari & Anuj Maheshwari

  3. Department of Anatomy, Era’s Lucknow Medical College & Hospital, Lucknow, India

    Vineeta Tewari

  4. Department of Psychiatry King George’s Medical University, Lucknow, India

    Rishabh Tiwari

  5. Dean, Hind Institute of Medical Sciences, Ataria, India

    Narsingh Verma

  6. Department of Internal Medicine, Integral Institute of Medical Sciences and Research, Lucknow, India

    Hemali Jha

  7. Himalayan Institute of Medical Sciences, Jollygrant, Dehradun, India

    Savneet Kaur

Authors
  1. Jay Tewari
    View author publications

    Search author on:PubMed Google Scholar

  2. Khalid Ahmad Qidwai
    View author publications

    Search author on:PubMed Google Scholar

  3. Ajoy Tewari
    View author publications

    Search author on:PubMed Google Scholar

  4. Anadika Rana
    View author publications

    Search author on:PubMed Google Scholar

  5. Vineeta Tewari
    View author publications

    Search author on:PubMed Google Scholar

  6. Vanshika Singh
    View author publications

    Search author on:PubMed Google Scholar

  7. Rishabh Tiwari
    View author publications

    Search author on:PubMed Google Scholar

  8. Anuj Maheshwari
    View author publications

    Search author on:PubMed Google Scholar

  9. Narsingh Verma
    View author publications

    Search author on:PubMed Google Scholar

  10. Hemali Jha
    View author publications

    Search author on:PubMed Google Scholar

  11. Savneet Kaur
    View author publications

    Search author on:PubMed Google Scholar

Contributions

This research project involved multiple contributors, each playing significant roles across various stages of the study. Jay Tewari, Khalid Ahmad Qidwai, Anadika Rana, Prof. Vineeta Tewari, Dr. Ajoy Tewari, Vanshika Singh, Rishabh Tiwari, Prof. Anuj Maheshwari, Prof. Narsingh Verma, Dr. Himali Jha, and Savneet Kaur were involved in conceptualizing and designing the study. In the literature search phase, all contributors except for Dr. Himali Jha and Savneet Kaur participated. The definition of intellectual content was primarily done by Jay Tewari, Prof. Vineeta Tewari, Dr. Ajoy Tewari, Prof. Anuj Maheshwari, and Prof. Narsingh Verma. The analysis and interpretation of results were performed by all the contributors. Manuscript writing was carried out by Jay Tewari, Khalid Ahmad Qidwai, and Anadika Rana, with support from Dr. Himali Jha and Savneet Kaur. Critical appraisal of the manuscript was undertaken by Prof. Vineeta Tewari, Dr. Ajoy Tewari, Vanshika Singh, Prof. Anuj Maheshwari, and Prof. Narsingh Verma. Finally, all contributors held accountability for the manuscript, ensuring the integrity and accuracy of the research findings.

Corresponding author

Correspondence to Khalid Ahmad Qidwai.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This is a systematic review and meta-analysis which needs no ethical approval. All the included studies had obtained ethical approval individually.

Additional information

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

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tewari, J., Qidwai, K.A., Tewari, A. et al. Association between antihypertensive drug use and the risk of depression: a systematic review and network meta-analysis. J Hum Hypertens 39, 246–253 (2025). https://doi.org/10.1038/s41371-025-01011-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41371-025-01011-x

Search

Advanced search

Quick links