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
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References
Adler S. Methyldopa-induced decrease in mental activity. Journal of the American Medical Association 230: 1428–1429, 1974
Akiskal H. Factors associated with incomplete recovery in primary depressive illness. Journal of Clinical Psychiatry 43: 266–271, 1982
Ananth J, Ghadirian AM. Drug-induced mood disorders. International Pharmacopsychiatry 15: 59–73, 1980
Avorn J, Everitt D, Weiss S. Increased antidepressant use in patients prescribed β-blockers. Journal of the American Medical Association 255: 357–360, 1986
Bant W. Do antihypertensive drugs really cause depression? Proceedings of the Royal Society of Medicine 67: 920–922, 1974
Bernstein S, Kaufman MR. A psychological analysis of apparent depression following rauwolfibrillationa therapy. Journal of Mt Sinai Hospital 27: 525, 1960
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
Cohen LM, Anderson G, White RF, et al. Enalapril and hypertension. American Journal of Psychiatry 141: 1012–1013, 1984
Colucci WS. Alpha-adrenergic receptor blockade with prazocin. Annals of Internal Medicine 97: 67–77, 1982
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
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
Davidson W. Drug hazards in the elderly. British Journal of Hospital Medicine 6: 83, 1971
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
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
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
Goodman AG, Gilman LS, Rall TW, Murad F (Eds) The pharmacological basis of therapeutics, p.649, MacMillan Publishing Company, New York, 1985
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
Henning M. Studies on the mode of action of alpha methyldopa. Acta Physiologica Scandinavica S322: 3–37, 1969
Henning M, Van Zweiten PA. Central hypotensive effect of alphamethyldopa. Journal of Pharmacy and Pharmacology 20: 409–417, 1968
Hoffman W. The behavioral side effects of the antihypertensive agents. American Family Physician 23: 213–216, 1981
Huapaya L, Ananth J. Depression associated with hypertension: a review. Psychiatric Journal of the University of Ottawa 5: 58–62, 1980
Itskovitz HS, Kochar MS, Anderson AJ, Rimm AA. Patterns of blood pressure in Milwaukee. Journal of the American Medical Association 238: 864, 1977
Janowsky DS, El-Yousef K, Davis M, Sekerke HJ. A cholinergic-adrenergic hypothesis of mania and depression. Lancet 2: 632, 1972
Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure. 1988 report. Archives of Internal Medicine 148: 1023–1038, 1988
Kostis JB. Angiotensin converting enzyme inhibitors. I. Pharmacology. American Heart Journal 116: 1580–1591, 1988a
Kostis JB. Angiotensin converting enzyme inhibitors. II. Clinical use. American Heart Journal 116: 1591–1605, 1988b
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
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
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
Mendels J, Frazer A. Brain biogenic amine depletion and mood. Archives of General Psychiatry 30: 447, 1974
Nicholls MG. Side effects and metabolic effects of converting-enzyme inhibitors. Clinical Experimental Hypertension Research (Part A) A9(2&3): 653–664, 1987
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
Okada F. Depression after treatment with thiazide diuretics for hypertension. American Journal of Psychiatry 142: 1101–1102, 1985
Olajide D, Lader M. Psychotropic effects of enalapril maleate in normal volunteers. Psychopharmacology (Berlin) 86: 374–376, 1985
Paykel ES, Fleminger R, Watson JP. Psychiatric side effects of antihypertensive drugs other than reserpine. Journal of Clinical Psychopharmacology 2: 14–39, 1982
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
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
Rabkin JG, Charles E, Kass F. Hypertension and DSM-III depression in psychiatric outpatients. American Journal of Psychiatry 140: 1072–1074, 1983
Raftos J, Bauer GE, Lewis RG, et al. Clonidine in the treatment of severe hypertension. Medical Journal of Australia 1: 786–793, 1973
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
Salzman C, van derKolk B. Treatment of depression. In Salzman C (Ed.) Clinical geriatric psychopharmacology, pp.77–115, McGraw-Hill, New York, 1984
Sandifer M. The hypertensive psychiatric patient: pharmacologic problems. Journal of Clinical Psychiatry 39: 700–702, 1987
Schildkraut JJ. The catecholamine hypothesis of affective disorder: a review of supporting evidence. American Journal of Psychiatry 122: 509–522, 1965
Schwarz D, Michel D, Strian F. Depressive reaktionen unter anti-hypertensive behandlung. Archiv fur Psychiatria und Nervenkrankheiten 218: 41–50, 1973
Snaith RP. Hypotensive drugs in the treatment of depression. British Journal of Clinical Pharmacology 3 (Suppl. 1): 73–74, 1976
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
Thornton WE. Tricyclic antidepressants and cardiovascular drug interactions. American Family Physician 20: 97–99, 1979
Waal HJ. Propranolol-induced depression. British Medical Journal 2: 50, 1967
Wheatley D, Balter M, Levine J, et al. Psychiatric aspects of hypertension. British Journal of Psychiatry 127: 327–336, 1975
Whitlock FA, Evans LEJ. Drugs and depression. Drugs 15: 53–71, 1976
Widmer R. Reserpine: the maligned antihypertensive drug. Journal of Family Practice 20(1): 81–83, 1985
Williams GH. Converting-enzyme inhibitors in the treatment of hypertension. New England Journal of Medicine 319: 1517–1525, 1988
Working Group on Hypertension in the Elderly. Statement on hypertension in the elderly. Journal of the American Medical Association 256: 70–74, 1986
Zubenko GS, Nixon RA. Mood-elevating effect of captopril in depressed patients. American Journal of Psychiatry 141: 110–111, 1984
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Beers, M.H., Passman, L.J. Antihypertensive Medications and Depression. Drugs 40, 792–799 (1990). https://doi.org/10.2165/00003495-199040060-00003
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DOI: https://doi.org/10.2165/00003495-199040060-00003