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. 1993 May;18(3):92–102.

Can drugs cause depression? A review of the evidence.

S B Patten 1, E J Love 1
PMCID: PMC1188504  PMID: 8499431

Abstract

Drug-induced depressive disorders are classified in the DSM-III-R as organic mood syndrome, depressed type. The ability of certain drugs to cause depression is of clinical relevance because organic mood syndrome is a component of the differential diagnosis of depressive symptoms. Consequently, psychiatric textbooks often provide different lists of drugs thought to be capable of causing depression. Strong evidence supporting the existence of causal associations is often lacking. There is no specific drug for which there is definitive evidence of a causal association with depressive symptoms or depressive disorders. Nevertheless, for a number of drugs, the evidence is suggestive, although not conclusively, of a causal association. Despite this, rational decisions about the continuation or discontinuation of drugs can often be made. In this paper, the literature is reviewed and guidelines are suggested for the management of patients with depressive symptoms which may be related to drugs.

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Selected References

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  1. Aarons R. D., Molinoff P. B. Changes in the density of beta adrenergic receptors in rat lymphocytes, heart and lung after chronic treatment with propranolol. J Pharmacol Exp Ther. 1982 May;221(2):439–443. [PubMed] [Google Scholar]
  2. Adams P. W., Rose D. P., Folkard J., Wynn V., Seed M., Strong R. Effect of pyridoxine hydrochloride (vitamin B 6 ) upon depression associated with oral contraception. Lancet. 1973 Apr 28;1(7809):899–904. [PubMed] [Google Scholar]
  3. Avorn J., Everitt D. E., Weiss S. Increased antidepressant use in patients prescribed beta-blockers. JAMA. 1986 Jan 17;255(3):357–360. [PubMed] [Google Scholar]
  4. Backon J. Prevalence of depression among Israeli alcoholics. J Clin Psychol. 1990 Jan;46(1):96–102. doi: 10.1002/1097-4679(199001)46:1<96::aid-jclp2270460115>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  5. Bant W. P. Antihypertensive drugs and depression: a reappraisal. Psychol Med. 1978 May;8(2):275–283. doi: 10.1017/s003329170001432x. [DOI] [PubMed] [Google Scholar]
  6. Bartels D., Glasser M., Wang A., Swanson P. Association between depression and propranolol use in ambulatory patients. Clin Pharm. 1988 Feb;7(2):146–150. [PubMed] [Google Scholar]
  7. Beers M. H., Passman L. J. Antihypertensive medications and depression. Drugs. 1990 Dec;40(6):792–799. doi: 10.2165/00003495-199040060-00003. [DOI] [PubMed] [Google Scholar]
  8. Belmaker R. H., Lerer B., Bannet J., Birmaher B. The effect of electroconvulsive shock at a clinically equivalent schedule on rat cortical beta-adrenoceptors. J Pharm Pharmacol. 1982 Apr;34(4):275–275. doi: 10.1111/j.2042-7158.1982.tb04246.x. [DOI] [PubMed] [Google Scholar]
  9. Bergstrom D. A., Kellar K. J. Effect of electroconvulsive shock on monoaminergic receptor binding sites in rat brain. Nature. 1979 Mar 29;278(5703):464–466. doi: 10.1038/278464a0. [DOI] [PubMed] [Google Scholar]
  10. Biegon A., Israeli M. Localization of the effects of electroconvulsive shock on beta-adrenoceptors in the rat brain. Eur J Pharmacol. 1986 Apr 29;123(3):329–334. doi: 10.1016/0014-2999(86)90705-3. [DOI] [PubMed] [Google Scholar]
  11. Biegon A., Israeli M. Regionally selective increases in beta-adrenergic receptor density in the brains of suicide victims. Brain Res. 1988 Feb 23;442(1):199–203. doi: 10.1016/0006-8993(88)91453-9. [DOI] [PubMed] [Google Scholar]
  12. Blacker C. V., Clare A. W. Depressive disorder in primary care. Br J Psychiatry. 1987 Jun;150:737–751. doi: 10.1192/bjp.150.6.737. [DOI] [PubMed] [Google Scholar]
  13. Bright R. A., Everitt D. E. Beta-blockers and depression. Evidence against an association. JAMA. 1992 Apr 1;267(13):1783–1787. doi: 10.1001/jama.267.13.1783. [DOI] [PubMed] [Google Scholar]
  14. Buckner J. C., Mandell W. Risk factors for depressive symptomatology in a drug using population. Am J Public Health. 1990 May;80(5):580–585. doi: 10.2105/ajph.80.5.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Bulpitt C. J., Dollery C. T. Side effects of hypotensive agents evaluated by a self-administered questionnaire. Br Med J. 1973 Sep 1;3(5878):485–490. doi: 10.1136/bmj.3.5878.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bunney W. E., Jr, Davis J. M. Norepinephrine in depressive reactions. A review. Arch Gen Psychiatry. 1965 Dec;13(6):483–494. doi: 10.1001/archpsyc.1965.01730060001001. [DOI] [PubMed] [Google Scholar]
  17. Carney R. M., Rich M. W., teVelde A., Saini J., Clark K., Freedland K. E. Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications. Am J Med. 1987 Aug;83(2):223–226. doi: 10.1016/0002-9343(87)90689-9. [DOI] [PubMed] [Google Scholar]
  18. Charney D. S., Heninger G. R., Sternberg D. E., Hafstad K. M., Giddings S., Landis D. H. Adrenergic receptor sensitivity in depression. Effects of clonidine in depressed patients and healthy subjects. Arch Gen Psychiatry. 1982 Mar;39(3):290–294. doi: 10.1001/archpsyc.1982.04290030030005. [DOI] [PubMed] [Google Scholar]
  19. Checkley S. A., Glass I. B., Thompson C., Corn T., Robinson P. The GH response to clonidine in endogenous as compared with reactive depression. Psychol Med. 1984 Nov;14(4):773–777. doi: 10.1017/s0033291700019747. [DOI] [PubMed] [Google Scholar]
  20. Checkley S. A., Slade A. P., Shur E. Growth hormone and other responses to clonidine in patients with endogenous depression. Br J Psychiatry. 1981 Jan;138:51–55. doi: 10.1192/bjp.138.1.51. [DOI] [PubMed] [Google Scholar]
  21. Chetwynd S. J., Pearson V. Alcohol problems among women working in the home: prevalence and predictors. Aust N Z J Psychiatry. 1983 Sep;17(3):259–264. doi: 10.3109/00048678309161282. [DOI] [PubMed] [Google Scholar]
  22. Clements-Jewery S. The development of cortical beta-adrenoceptor subsensitivity in the rat by chronic treatment with trazodone, doxepin and mianserine. Neuropharmacology. 1978 Sep;17(9):779–781. doi: 10.1016/0028-3908(78)90094-1. [DOI] [PubMed] [Google Scholar]
  23. Cordess C., Folstein M., Drachman D. Psychiatric effects of alternate day steroid therapy. Br J Psychiatry. 1981 Jun;138:504–506. doi: 10.1192/bjp.138.6.504. [DOI] [PubMed] [Google Scholar]
  24. DeMuth G. W., Ackerman S. H. alpha-Methyldopa and depression: a clinical study and review of the literature. Am J Psychiatry. 1983 May;140(5):534–538. doi: 10.1176/ajp.140.5.534. [DOI] [PubMed] [Google Scholar]
  25. Deakin J. F., Owen F., Cross A. J., Dashwood M. J. Studies on possible mechanisms of action of electroconvulsive therapy; effects of repeated electrically induced seizures on rat brain receptors for monoamines and other neurotransmitters. Psychopharmacology (Berl) 1981;73(4):345–349. doi: 10.1007/BF00426463. [DOI] [PubMed] [Google Scholar]
  26. Deykin E. Y., Levy J. C., Wells V. Adolescent depression, alcohol and drug abuse. Am J Public Health. 1987 Feb;77(2):178–182. doi: 10.2105/ajph.77.2.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Doyle M. C., George A. J., Ravindran A. V., Philpott R. Platelet alpha 2-adrenoreceptor binding in elderly depressed patients. Am J Psychiatry. 1985 Dec;142(12):1489–1490. doi: 10.1176/ajp.142.12.1489. [DOI] [PubMed] [Google Scholar]
  28. Gangat A. E., Simpson M. A., Naidoo L. R. Medication as a potential cause of depression. S Afr Med J. 1986 Aug 16;70(4):224–226. [PubMed] [Google Scholar]
  29. García-Sevilla J. A., García-Vallejo P., Guimon J. Enhanced alpha 2-adrenoceptor-mediated platelet aggregation in patients with major depressive disorder. Eur J Pharmacol. 1983 Oct 28;94(3-4):359–360. doi: 10.1016/0014-2999(83)90430-2. [DOI] [PubMed] [Google Scholar]
  30. Gawin F. H., Kleber H. D. Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Clinical observations. Arch Gen Psychiatry. 1986 Feb;43(2):107–113. doi: 10.1001/archpsyc.1986.01800020013003. [DOI] [PubMed] [Google Scholar]
  31. Glaubiger G., Lefkowitz R. J. Elevated beta-adrenergic receptor number after chronic propranolol treatment. Biochem Biophys Res Commun. 1977 Sep 23;78(2):720–725. doi: 10.1016/0006-291x(77)90238-8. [DOI] [PubMed] [Google Scholar]
  32. Goldzieher J. W., Moses L. E., Averkin E., Scheel C., Taber B. Z. Nervousness and depression attributed to oral contraceptives: a double-blind, placebo-controlled study. Am J Obstet Gynecol. 1971 Dec 15;111(8):1013–1020. doi: 10.1016/0002-9378(71)90096-2. [DOI] [PubMed] [Google Scholar]
  33. Gotham A. M., Brown R. G., Marsden C. D. Depression in Parkinson's disease: a quantitative and qualitative analysis. J Neurol Neurosurg Psychiatry. 1986 Apr;49(4):381–389. doi: 10.1136/jnnp.49.4.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Greden J. F., Fontaine P., Lubetsky M., Chamberlin K. Anxiety and depression associated with caffeinism among psychiatric inpatients. Am J Psychiatry. 1978 Aug;135(8):963–966. doi: 10.1176/ajp.135.8.963. [DOI] [PubMed] [Google Scholar]
  35. Griffin S. J., Friedman M. J. Depressive symptoms in propranolol users. J Clin Psychiatry. 1986 Sep;47(9):453–457. [PubMed] [Google Scholar]
  36. Haack M. R., Harford T. C., Parker D. A. Alcohol use and depression symptoms among female nursing students. Alcohol Clin Exp Res. 1988 Jun;12(3):365–367. doi: 10.1111/j.1530-0277.1988.tb00209.x. [DOI] [PubMed] [Google Scholar]
  37. Heal D. J., Butler S. A., Hurst E. M., Buckett W. R. Antidepressant treatments, including sibutramine hydrochloride and electroconvulsive shock, decrease beta 1- but not beta 2-adrenoceptors in rat cortex. J Neurochem. 1989 Oct;53(4):1019–1025. doi: 10.1111/j.1471-4159.1989.tb07389.x. [DOI] [PubMed] [Google Scholar]
  38. Healy D., Carney P. A., Leonard B. E. Monoamine-related markers of depression: changes following treatment. J Psychiatr Res. 1982;17(3):251–260. doi: 10.1016/0022-3956(82)90003-6. [DOI] [PubMed] [Google Scholar]
  39. James J. E., Crosbie J. Somatic and psychological health implications of heavy caffeine use. Br J Addict. 1987 May;82(5):503–509. doi: 10.1111/j.1360-0443.1987.tb01507.x. [DOI] [PubMed] [Google Scholar]
  40. Kamerow D. B. Anxiety and depression in the medical setting: an overview. Med Clin North Am. 1988 Jul;72(4):745–751. doi: 10.1016/s0025-7125(16)30742-8. [DOI] [PubMed] [Google Scholar]
  41. Kay C. R. The Royal College of General Practitioners' Oral Contraception Study: some recent observations. Clin Obstet Gynaecol. 1984 Dec;11(3):759–786. [PubMed] [Google Scholar]
  42. Kellar K. J., Bergstrom D. A. Electroconvulsive shock: effects on biochemical correlates of neurotransmitter receptors in rat brain. Neuropharmacology. 1983 Mar;22(3 Spec No):401–406. doi: 10.1016/0028-3908(83)90189-2. [DOI] [PubMed] [Google Scholar]
  43. Kellar K. J., Cascio C. S., Bergstrom D. A., Butler J. A., Iadarola P. Electroconvulsive shock and reserpine: effects on beta-adrenergic receptors in rat brain. J Neurochem. 1981 Oct;37(4):830–836. doi: 10.1111/j.1471-4159.1981.tb04468.x. [DOI] [PubMed] [Google Scholar]
  44. Kendler K. S., Martin N. G., Heath A. C., Handelsman D., Eaves L. J. A twin study of the psychiatric side effects of oral contraceptives. J Nerv Ment Dis. 1988 Mar;176(3):153–160. doi: 10.1097/00005053-198803000-00003. [DOI] [PubMed] [Google Scholar]
  45. Leeton J., Leinkram C., Stiglitz J. The relationship of oral contraception to depression. Aust N Z J Obstet Gynaecol. 1971 Nov;11(4):237–240. doi: 10.1111/j.1479-828x.1971.tb00485.x. [DOI] [PubMed] [Google Scholar]
  46. Leeton J. The relationship of oral contraception to depressive symptoms. Aust N Z J Obstet Gynaecol. 1973 May;13(2):115–120. doi: 10.1111/j.1479-828x.1973.tb02291.x. [DOI] [PubMed] [Google Scholar]
  47. Mann J. J., Stanley M., McBride P. A., McEwen B. S. Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry. 1986 Oct;43(10):954–959. doi: 10.1001/archpsyc.1986.01800100048007. [DOI] [PubMed] [Google Scholar]
  48. Mayeux R., Stern Y., Rosen J., Leventhal J. Depression, intellectual impairment, and Parkinson disease. Neurology. 1981 Jun;31(6):645–650. doi: 10.1212/wnl.31.6.645. [DOI] [PubMed] [Google Scholar]
  49. McMillen B. A., Warnack W., German D. C., Shore P. A. Effects of chronic desipramine treatment on rat brain noradrenergic responses to alpha-adrenergic drugs. Eur J Pharmacol. 1980 Feb 8;61(3):239–246. doi: 10.1016/0014-2999(80)90126-0. [DOI] [PubMed] [Google Scholar]
  50. Mindham R. H., Marsden C. D., Parkes J. D. Psychiatric symptoms during l-dopa therapy for Parkinson's disease and their relationship to physical disability. Psychol Med. 1976 Feb;6(1):23–33. doi: 10.1017/s0033291700007467. [DOI] [PubMed] [Google Scholar]
  51. Mino Y., Yasuda N., Fujimura T., Ohara H. Caffeine consumption and anxiety and depressive symptomatology among medical students. Arukoru Kenkyuto Yakubutsu Ison. 1990 Dec;25(6):486–496. [PubMed] [Google Scholar]
  52. Mishra R., Janowsky A., Sulser F. Subsensitivity of the norepinephrine receptor-coupled adenylate cyclase system in brain: effects of nisoxetine versus fluoxetine. Eur J Pharmacol. 1979 Dec 20;60(4):379–382. doi: 10.1016/0014-2999(79)90246-2. [DOI] [PubMed] [Google Scholar]
  53. Mitchell P. B., Bearn J. A., Corn T. H., Checkley S. A. Growth hormone response to clonidine after recovery in patients with endogenous depression. Br J Psychiatry. 1988 Jan;152:34–38. doi: 10.1192/bjp.152.1.34. [DOI] [PubMed] [Google Scholar]
  54. Nelson D. R., Thomas D. R., Johnson A. M. Pharmacological effects of paroxetine after repeated administration to animals. Acta Psychiatr Scand Suppl. 1989;350:21–23. doi: 10.1111/j.1600-0447.1989.tb07162.x. [DOI] [PubMed] [Google Scholar]
  55. Nimgaonkar V. L., Goodwin G. M., Davies C. L., Green A. R. Down-regulation of beta-adrenoceptors in rat cortex by repeated administration of desipramine, electroconvulsive shock and clenbuterol requires 5-HT neurones but not 5-HT. Neuropharmacology. 1985 Apr;24(4):279–283. doi: 10.1016/0028-3908(85)90132-7. [DOI] [PubMed] [Google Scholar]
  56. Oswald I., Lewis S. A., Dunleavy D. L., Brezinova V., Briggs M. Drugs of dependence though not of abuse: fenfluramine and imipramine. Br Med J. 1971 Jul 10;3(5766):70–73. doi: 10.1136/bmj.3.5766.70. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Pandey G. N., Heinze W. J., Brown B. D., Davis J. M. Electroconvulsive shock treatment decrease beta-adrenergic receptor sensitivity in rat brain. Nature. 1979 Jul 19;280(5719):234–235. doi: 10.1038/280234a0. [DOI] [PubMed] [Google Scholar]
  58. Parker D. A., Parker E. S., Harford T. C., Farmer G. C. Alcohol use and depression symptoms among employed men and women. Am J Public Health. 1987 Jun;77(6):704–707. doi: 10.2105/ajph.77.6.704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Patten S. B., Lamarre C. J. Can drug-induced depressions be identified by their clinical features? Can J Psychiatry. 1992 Apr;37(3):213–215. [PubMed] [Google Scholar]
  60. Petrie W. M., Maffucci R. J., Woosley R. L. Propranolol and depression. Am J Psychiatry. 1982 Jan;139(1):92–94. doi: 10.1176/ajp.139.1.92. [DOI] [PubMed] [Google Scholar]
  61. Pollack M. H., Rosenbaum J. F., Cassem N. H. Propranolol and depression revisited: three cases and a review. J Nerv Ment Dis. 1985 Feb;173(2):118–119. doi: 10.1097/00005053-198502000-00010. [DOI] [PubMed] [Google Scholar]
  62. Pope H. G., Jr, Katz D. L. Affective and psychotic symptoms associated with anabolic steroid use. Am J Psychiatry. 1988 Apr;145(4):487–490. doi: 10.1176/ajp.145.4.487. [DOI] [PubMed] [Google Scholar]
  63. Powell B. J., Penick E. C., Othmer E., Bingham S. F., Rice A. S. Prevalence of additional psychiatric syndromes among male alcoholics. J Clin Psychiatry. 1982 Oct;43(10):404–407. [PubMed] [Google Scholar]
  64. Riva M. A., Creese I. Reevaluation of the regulation of beta-adrenergic receptor binding by desipramine treatment. Mol Pharmacol. 1989 Jul;36(1):211–218. [PubMed] [Google Scholar]
  65. Robins A. H., Lucke W., McFadyen M. L., Wright J. P. Effect of the H2-receptor antagonist ranitidine on depression and anxiety in duodenal ulcer patients. Postgrad Med J. 1984 May;60(703):353–355. doi: 10.1136/pgmj.60.703.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Sarai K., Frazer A., Brunswick D., Mendels J. Desmethylimipramine-induced decrease in beta-adrenergic receptor binding in rat cerebral cortex. Biochem Pharmacol. 1978;27(17):2179–2181. doi: 10.1016/0006-2952(78)90293-9. [DOI] [PubMed] [Google Scholar]
  67. Schleifer S. J., Slater W. R., Macari-Hinson M. M., Coyle D. A., Kahn M., Zucker H. D., Gorlin R. Digitalis and beta-blocking agents: effects on depression following myocardial infarction. Am Heart J. 1991 May;121(5):1397–1402. doi: 10.1016/0002-8703(91)90144-7. [DOI] [PubMed] [Google Scholar]
  68. Sellinger-Barnette M. M., Mendels J., Frazer A. The effect of psychoactive drugs on beta-adrenergic receptor binding sites in rat brain. Neuropharmacology. 1980 May;19(5):447–454. doi: 10.1016/0028-3908(80)90052-0. [DOI] [PubMed] [Google Scholar]
  69. Sethy V. H., Harris D. W. Effect of norepinephrine uptake blocker on beta-adrenergic receptors of the rat cerebral cortex. Eur J Pharmacol. 1981 Oct 15;75(1):53–56. doi: 10.1016/0014-2999(81)90344-7. [DOI] [PubMed] [Google Scholar]
  70. Severson J. A., Pittman R. N., Gal J., Molinoff P. B., Finch C. E. Genetic influence on the regulation of beta adrenergic receptors in mice. J Pharmacol Exp Ther. 1986 Jan;236(1):24–29. [PubMed] [Google Scholar]
  71. Snaith R. P., McCoubrie M. Antihypertensive drugs and depression. Psychol Med. 1974 Nov;4(4):393–398. doi: 10.1017/s0033291700045840. [DOI] [PubMed] [Google Scholar]
  72. Spyraki C., Fibiger H. C. Functional evidence for subsensitivity of noradrenergic alpha 2 receptors after chronic desipramine treatment. Life Sci. 1980 Nov 17;27(20):1863–1867. doi: 10.1016/0024-3205(80)90431-2. [DOI] [PubMed] [Google Scholar]
  73. Starkstein S. E., Preziosi T. J., Bolduc P. L., Robinson R. G. Depression in Parkinson's disease. J Nerv Ment Dis. 1990 Jan;178(1):27–31. doi: 10.1097/00005053-199001000-00005. [DOI] [PubMed] [Google Scholar]
  74. Steel J. M., Briggs M. Withdrawal depression in obese patients after fenfluramine treatment. Br Med J. 1972 Jul 1;3(5817):26–27. doi: 10.1136/bmj.3.5817.26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Stoudemire A., Brown J. T., Harris R. T., Blessing-Feussner C., Roberts J. H., Nichols J. C., Houpt J. L. Propranolol and depression: a reevaluation based on a pilot clinical trial. Psychiatr Med. 1984 Jun;2(2):211–218. [PubMed] [Google Scholar]
  76. Thiessen B. Q., Wallace S. M., Blackburn J. L., Wilson T. W., Bergman U. Increased prescribing of antidepressants subsequent to beta-blocker therapy. Arch Intern Med. 1990 Nov;150(11):2286–2290. [PubMed] [Google Scholar]
  77. Weiss R. D., Mirin S. M., Michael J. L., Sollogub A. C. Psychopathology in chronic cocaine abusers. Am J Drug Alcohol Abuse. 1986;12(1-2):17–29. doi: 10.3109/00952998609083740. [DOI] [PubMed] [Google Scholar]
  78. Wells K. B., Hays R. D., Burnam M. A., Rogers W., Greenfield S., Ware J. E., Jr Detection of depressive disorder for patients receiving prepaid or fee-for-service care. Results from the Medical Outcomes Study. JAMA. 1989 Dec 15;262(23):3298–3302. [PubMed] [Google Scholar]
  79. Widmer R. B. Reserpine: the maligned antihypertensive drug. J Fam Pract. 1985 Jan;20(1):81–83. [PubMed] [Google Scholar]
  80. Winstead D. K. Coffee consumption among psychiatric inpatients. Am J Psychiatry. 1976 Dec;133(12):1447–1450. doi: 10.1176/ajp.133.12.1447. [DOI] [PubMed] [Google Scholar]
  81. Wynn V. Vitamins and oral contraceptive use. Lancet. 1975 Mar 8;1(7906):561–564. doi: 10.1016/s0140-6736(75)91570-6. [DOI] [PubMed] [Google Scholar]

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