Skip to main content
Log in

Antihypertensive Medications and Depression

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

The association between antihypertensive medications and depression has been recognised for over 40 years. More recently, our understanding of the role of neurotrnsmitters in the aetiology of depression has helped us understand how antihypertensive drugs cause depression. Biogenic amine depletion is now believed to underlie the organic nature of depression, and many of the drugs used to treat hypertension interfere with this system

There is now compelling evidence that both reserpine and α-methyldopa can induce or worsen depression through their actions on the central nervous system. β-Blockers have also been implicated, but the data supporting the link between these drugs and depression are not as certain. Guanethidine, clonidine, hydralazine, and prazosin appear to pose little risk in causing depression, although rare occurrences have been reported. Diuretics, calcium channel blockers, and angiotensin converting enzyme (ACE) inhibitors appear to have the lowest association with depression and are therefore the drugs of choice when depression is a risk

Physicians should know which drugs introduce the risk of causing or worsening depression. The wide array of medications now available to treat hypertension offers alternatives that pose low risk. All patients receiving medication to treat hypertension should be evaluated periodically for depression, and if depression occurs, medication should be suspected as playing a role in its aetiology

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adler S. Methyldopa-induced decrease in mental activity. Journal of the American Medical Association 230: 1428–1429, 1974

    Article  PubMed  CAS  Google Scholar 

  • Akiskal H. Factors associated with incomplete recovery in primary depressive illness. Journal of Clinical Psychiatry 43: 266–271, 1982

    PubMed  CAS  Google Scholar 

  • Ananth J, Ghadirian AM. Drug-induced mood disorders. International Pharmacopsychiatry 15: 59–73, 1980

    PubMed  CAS  Google Scholar 

  • Avorn J, Everitt D, Weiss S. Increased antidepressant use in patients prescribed β-blockers. Journal of the American Medical Association 255: 357–360, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bant W. Do antihypertensive drugs really cause depression? Proceedings of the Royal Society of Medicine 67: 920–922, 1974

    Google Scholar 

  • Bernstein S, Kaufman MR. A psychological analysis of apparent depression following rauwolfibrillationa therapy. Journal of Mt Sinai Hospital 27: 525, 1960

    Google Scholar 

  • Callender JS, Hodsman GP, Hutcheson MJ, et al. Mood changes during captopril therapy for hypertension: a double-blind pilot study. Hypertension 5: III–90–93, 1983

    Google Scholar 

  • Cohen LM, Anderson G, White RF, et al. Enalapril and hypertension. American Journal of Psychiatry 141: 1012–1013, 1984

    PubMed  CAS  Google Scholar 

  • Colucci WS. Alpha-adrenergic receptor blockade with prazocin. Annals of Internal Medicine 97: 67–77, 1982

    PubMed  CAS  Google Scholar 

  • Croog SH, Levine S, Testa MA. The effects of antihypertensive therapy on the quality of life. New England Journal of Medicine 314: 1657–1664, 1986

    Article  PubMed  CAS  Google Scholar 

  • Cruickshank JM, Prichard BNC. Adverse reactions. In Beta-blockers in clinical practice, p.792, Churchill Livingston, Edinburgh, 1988a

  • Cruickshank JM, Prichard BNC. Beta-blockers in clinical practice, pp. 812–813, Churchill Livingston, Edinburgh, 1988b

    Google Scholar 

  • Davidson W. Drug hazards in the elderly. British Journal of Hospital Medicine 6: 83, 1971

    Google Scholar 

  • Gengo FM, Fagan SC, de Padova A, et al. The effect of beta-blockers on mental performance in older hypertensive patients. Archives of Internal Medicine 148: 779–784, 1988

    Article  PubMed  CAS  Google Scholar 

  • Geppetti P, Spillantini MG, Frilli S, et al. Acute oral captopril inhibits angiotensin converting enzyme activity in human cerebrovascular fluid. Journal of Hypertension 5: 151–154, 1987

    Article  PubMed  CAS  Google Scholar 

  • Glorioso N, Dessi-Fulgheri P, Alagna S, et al. Angiotensin converting enzyme inhibition reduces ACTH release due to hypoglycemia. Clinical and Experimental Hypertension Research (Part A) A9(2&3): 665–670, 1987

    Google Scholar 

  • Goodman AG, Gilman LS, Rall TW, Murad F (Eds) The pharmacological basis of therapeutics, p.649, MacMillan Publishing Company, New York, 1985

    Google Scholar 

  • Goodwin FK, Ebert MH, Bunney WE. Mental effects of reserpine in man: a review: In Shader RI (Ed.) Psychiatric complications of medical drugs, pp. 73–101, Raven Press, New York, 1972

    Google Scholar 

  • Henning M. Studies on the mode of action of alpha methyldopa. Acta Physiologica Scandinavica S322: 3–37, 1969

    Google Scholar 

  • Henning M, Van Zweiten PA. Central hypotensive effect of alphamethyldopa. Journal of Pharmacy and Pharmacology 20: 409–417, 1968

    Article  PubMed  CAS  Google Scholar 

  • Hoffman W. The behavioral side effects of the antihypertensive agents. American Family Physician 23: 213–216, 1981

    Google Scholar 

  • Huapaya L, Ananth J. Depression associated with hypertension: a review. Psychiatric Journal of the University of Ottawa 5: 58–62, 1980

    Google Scholar 

  • Itskovitz HS, Kochar MS, Anderson AJ, Rimm AA. Patterns of blood pressure in Milwaukee. Journal of the American Medical Association 238: 864, 1977

    Article  PubMed  CAS  Google Scholar 

  • Janowsky DS, El-Yousef K, Davis M, Sekerke HJ. A cholinergic-adrenergic hypothesis of mania and depression. Lancet 2: 632, 1972

    Article  PubMed  CAS  Google Scholar 

  • Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure. 1988 report. Archives of Internal Medicine 148: 1023–1038, 1988

    Article  Google Scholar 

  • Kostis JB. Angiotensin converting enzyme inhibitors. I. Pharmacology. American Heart Journal 116: 1580–1591, 1988a

    Article  PubMed  CAS  Google Scholar 

  • Kostis JB. Angiotensin converting enzyme inhibitors. II. Clinical use. American Heart Journal 116: 1591–1605, 1988b

    Article  PubMed  CAS  Google Scholar 

  • Larochelle P, Bass MJ, Birkett NH, De Champlain J, Myers MG. Recommendations from the Consensus Conference on Hypertension in the Elderly. Canadian Medical Association Journal 135: 741–745, 1986

    PubMed  CAS  Google Scholar 

  • McNeil G, Shaw P, Dock D. Substitution of atenolol for propranolol in a case of propranolol related depression. American Journal of Psychiatry 139: 1187–1188, 1982

    PubMed  CAS  Google Scholar 

  • Medical Research Council Working Party on Mild to Moderate Hypertension. Adverse reactions to bendrofluazide and propranolol for the treatment of mild hypertension. Lancet 2: 539–543, 1981

    Google Scholar 

  • Mendels J, Frazer A. Brain biogenic amine depletion and mood. Archives of General Psychiatry 30: 447, 1974

    Article  PubMed  CAS  Google Scholar 

  • Nicholls MG. Side effects and metabolic effects of converting-enzyme inhibitors. Clinical Experimental Hypertension Research (Part A) A9(2&3): 653–664, 1987

    Article  Google Scholar 

  • Norman JA, Autry WL, Barbaz BS. Angiotensin-converting enzyme inhibitors potentiate the analgesic activity of [met]-en-kephalin-arg6-phe7 by inhibiting its degradation in mouse brain. Molecular Pharmacology 28: 521–526, 1985

    PubMed  CAS  Google Scholar 

  • Okada F. Depression after treatment with thiazide diuretics for hypertension. American Journal of Psychiatry 142: 1101–1102, 1985

    PubMed  CAS  Google Scholar 

  • Olajide D, Lader M. Psychotropic effects of enalapril maleate in normal volunteers. Psychopharmacology (Berlin) 86: 374–376, 1985

    Article  CAS  Google Scholar 

  • Paykel ES, Fleminger R, Watson JP. Psychiatric side effects of antihypertensive drugs other than reserpine. Journal of Clinical Psychopharmacology 2: 14–39, 1982

    Article  PubMed  CAS  Google Scholar 

  • Pollack MH, Rosenbaum JF, Cassem NH. Propranolol and depression revisited: three cases and a review. Journal of Nervous and Mental Disease 173: 118–119, 1985

    Article  PubMed  CAS  Google Scholar 

  • Prichard BCN, Johnston AW, et al. Bethanidine, guanethidine, and methyldopa in the treatment of hypertension: a within-patient comparison. British Medical Journal 1: 135, 1968

    Article  PubMed  CAS  Google Scholar 

  • Rabkin JG, Charles E, Kass F. Hypertension and DSM-III depression in psychiatric outpatients. American Journal of Psychiatry 140: 1072–1074, 1983

    PubMed  CAS  Google Scholar 

  • Raftos J, Bauer GE, Lewis RG, et al. Clonidine in the treatment of severe hypertension. Medical Journal of Australia 1: 786–793, 1973

    PubMed  CAS  Google Scholar 

  • Salzman C, Shader R. Depression in the elderly. II. Possible drug etiologies: differential diagnostic criteria. Journal of the American Geriatrics Society 26: 303–308, 1978

    PubMed  CAS  Google Scholar 

  • Salzman C, van derKolk B. Treatment of depression. In Salzman C (Ed.) Clinical geriatric psychopharmacology, pp.77–115, McGraw-Hill, New York, 1984

    Google Scholar 

  • Sandifer M. The hypertensive psychiatric patient: pharmacologic problems. Journal of Clinical Psychiatry 39: 700–702, 1987

    Google Scholar 

  • Schildkraut JJ. The catecholamine hypothesis of affective disorder: a review of supporting evidence. American Journal of Psychiatry 122: 509–522, 1965

    PubMed  CAS  Google Scholar 

  • Schwarz D, Michel D, Strian F. Depressive reaktionen unter anti-hypertensive behandlung. Archiv fur Psychiatria und Nervenkrankheiten 218: 41–50, 1973

    Article  CAS  Google Scholar 

  • Snaith RP. Hypotensive drugs in the treatment of depression. British Journal of Clinical Pharmacology 3 (Suppl. 1): 73–74, 1976

    Article  PubMed  CAS  Google Scholar 

  • Takahashi H, Yoshimura M. The central nervous system and effective antihypertensive effects of a calcium channel blocker. Journal of Cardiovascular Pharmacology 10 (Suppl): 129–133, 1987

    Google Scholar 

  • Thornton WE. Tricyclic antidepressants and cardiovascular drug interactions. American Family Physician 20: 97–99, 1979

    PubMed  CAS  Google Scholar 

  • Waal HJ. Propranolol-induced depression. British Medical Journal 2: 50, 1967

    Article  PubMed  CAS  Google Scholar 

  • Wheatley D, Balter M, Levine J, et al. Psychiatric aspects of hypertension. British Journal of Psychiatry 127: 327–336, 1975

    Article  PubMed  CAS  Google Scholar 

  • Whitlock FA, Evans LEJ. Drugs and depression. Drugs 15: 53–71, 1976

    Article  Google Scholar 

  • Widmer R. Reserpine: the maligned antihypertensive drug. Journal of Family Practice 20(1): 81–83, 1985

    PubMed  CAS  Google Scholar 

  • Williams GH. Converting-enzyme inhibitors in the treatment of hypertension. New England Journal of Medicine 319: 1517–1525, 1988

    Article  PubMed  CAS  Google Scholar 

  • Working Group on Hypertension in the Elderly. Statement on hypertension in the elderly. Journal of the American Medical Association 256: 70–74, 1986

    Article  Google Scholar 

  • Zubenko GS, Nixon RA. Mood-elevating effect of captopril in depressed patients. American Journal of Psychiatry 141: 110–111, 1984

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beers, M.H., Passman, L.J. Antihypertensive Medications and Depression. Drugs 40, 792–799 (1990). https://doi.org/10.2165/00003495-199040060-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199040060-00003

Keywords

Navigation