Skip to main content

The Risk-Benefit Assessment of Antidepressant Drugs

Summary

Antidepressant drugs in common use are reviewed in terms of their risks and benefits. A simple classification divides these into tricyclic antidepressants, monoamine oxidase inhibitors and second generation antidepressants.

Risks may arise from the correct use of an antidepressant, from its incorrect or inappropriate use, or due to its failure to reverse the depression. The greatest risk is to leave the depression untreated. Risks due to adverse drug effects are generally predictable but in some cases are unexpected and have led to the withdrawal of the drug from the market.

Assessing the benefits of antidepressant drugs is more difficult. Rating scales can be used in this context and the fact that the majority of antidepressant drugs have a similar degree of efficacy serves to emphasise the importance of making a risk-benefit assessment of each drug. This has been presented for the more widely used drugs. Safety in overdose is a particularly important benefit.

The ideal antidepressant should specifically reverse depressive illness without toxic effects. Although no drug at present measures up to this it is clear that antidepressants should be prescribed, as their benefits outweigh their risks.

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

References

  • Arnoff GM. Trazodone associated with priapism. Lancet 1: 856, 1984

    Article  Google Scholar 

  • Avery D, Winokur G. Mortality in depressed patients treated with electroconvulsive therapy and antidepressants. Archives of General Psychiatry 33: 1029, 1976

    PubMed  Article  CAS  Google Scholar 

  • Baldwin RC, Jolley DJ. The prognosis of depression in old age. British Journal of Psychiatry 149: 574–583, 1986

    PubMed  Article  CAS  Google Scholar 

  • Barnes TRE, Greenwood DT. Viloxazine and migraine. Lancet 2: 1368, 1979

    PubMed  Article  CAS  Google Scholar 

  • Barraclough BM, Bunch J, Nelson B, Sainsbury P. 100 cases of suicide: clinical aspects. British Journal of Psychiatry 125: 355–373, 1974

    PubMed  Article  CAS  Google Scholar 

  • Blackwell B. Antidepressant drugs. In Dukes MNG (Ed.) Meyler’s side effects of drugs, 10th ed., pp. 25–61, Elsevier Science Publishers BV, 1984

  • Blackwell B. Antidepressant drugs. In Dukes MNG (Ed.) Side effects of drugs, Annual 9, pp. 19–26, Elsevier Science Publishers BV, 1985

  • Burgess CD, Montgomery S, Wadsworth J, Turner P. Cardiovascular effects of mianserin, zimeldine, nomifensine, in depressed patients. Postgraduate Medical Journal 55: 704–708, 1979

    PubMed  Article  CAS  Google Scholar 

  • Burrows GD, Vohra J, Hunt D, et al. Cardiac effects of different tricyclic antidepressant drugs. British Journal of Psychiatry 129: 335–341, 1976

    PubMed  Article  CAS  Google Scholar 

  • Cassidy SL, Henry JA. Fatal toxicity of antidepressant drugs in overdose. British Medical Journal, in press, 1987

  • Charney DS, Heninger GR, Sternberg DE, Landis H. Abrupt discontinuation of tricyclic antidepressant drugs: evidence for noradrenergic hyperactivity. British Journal of Psychiatry 141: 377–386, 1982

    PubMed  Article  CAS  Google Scholar 

  • Coccaro EF, Siever LJ. Second generation antidepressants: a comparative review. Journal of Clinical Pharmacology 25: 241–260, 1985

    PubMed  CAS  Google Scholar 

  • Costa D, Mogos I, Toma T. Efficacy and safety of mianserin in treatment of depression of women with cancer. Acta Psychiatrica Scandinavica 72 (Suppl. 320): 85–92, 1985

    Article  Google Scholar 

  • Coull DC, Crooks J, Dingwall-Fordyce I, Scott AM, Weir RD. Amitriptyline and cardiac disease: risks of sudden death identified by monitoring system. Lancet 2: 590–591, 1970

    PubMed  Article  CAS  Google Scholar 

  • Craft AW. Circumstances surrounding deaths from accidental poisoning, 1974–1980. Archives of Disease in Childhood 58: 544–546, 1983

    PubMed  Article  CAS  Google Scholar 

  • Crome P. Poisoning due to tricyclic antidepressant overdosage: clinical presentation and treatment. Medical Toxicology 1: 261–285, 1986

    PubMed  CAS  Google Scholar 

  • Crome P, Ali P. Clinical features and management of self-poisoning with newer antidepressants. Medical Toxicology 1: 411–420, 1986

    PubMed  CAS  Google Scholar 

  • Crome P, Newman B. Poisoning with maprotiline and mianserin. British Medical Journal 2: 260, 1977

    PubMed  Article  CAS  Google Scholar 

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

    PubMed  Article  CAS  Google Scholar 

  • CSM Update. Adverse reactions to antidepressants. British Medical Journal 291: 1638, 1985

    Article  Google Scholar 

  • CSM Update. Withdrawal of nomifensine. British Medical Journal 293: 41, 1986

    Article  Google Scholar 

  • Data Sheet 1986. Revised data sheet issued by Organon Laboratories in agreement with Committee on Safety of Medicines — May 1986

  • Davies RK, Tucker DJ, Harrow M, Detre TP. Confusional episodes and antidepressant medication. American Journal of Psychiatry 128: 127, 1971

    Google Scholar 

  • Editorial. Product News — Welbutrin launch delayed. Scrip No. 1083 (March 10): 20, 1986

  • Editorial. La courageuse décision de Pharmuka. Gazette Medicale 92: 27, 1985

  • Evans DL, Davidson J, Raft D. Early and late side effects of phenelzine. Journal of Clinical Psychopharmacology 2: 208–210, 1982

    PubMed  Article  CAS  Google Scholar 

  • Feldmann HS, Denber HCB. Long-term study of fluvoxamine: a new rapid-acting antidepressant. International Pharmacopsychiatry 17: 114–122, 1982

    PubMed  CAS  Google Scholar 

  • Georgotas A, McCue RE, Hapworth W, et al. Comparative efficacy and safety of MAOIs v TCAs in treating depression in the elderly. Biological Psychiatry 21: 1155–1166, 1986

    PubMed  Article  CAS  Google Scholar 

  • Gerner RH. Present status of drug therapy of depression in late life. Journal of Affective Disorders (Suppl. 1): S23-S31, 1985

  • Gerner R, Eastbrook W, Steuer J, Jarvik L. Treatment of geriatric depression with trazodone, imipramine and placebo: a double-blind study. Journal of Clinical Psychiatry 41: 216–220, 1980

    PubMed  CAS  Google Scholar 

  • Goldberg D. Identifying psychiatric illness among general medical patients. British Medical Journal 291: 161–162, 1985

    PubMed  Article  CAS  Google Scholar 

  • Griffin N, Draper RJ, Webb MGT. Addiction to tranylcypromine. British Medical Journal 283: 346, 1981

    PubMed  Article  CAS  Google Scholar 

  • Gruter W, Poldinger W. Maprotiline. Modern Problems in Pharmacopsychiatry 18: 17–48, 1982

    CAS  Google Scholar 

  • Guy W(Ed.). CGI Clinical Global Impressions. ECDEU assessment manual for psychopharmacology (DHEW Publication no. 76338), pp. 218–222, Department of Health, Education and Welfare, Washington, D.C., 1976

    Google Scholar 

  • Guze SB, Robins E. Suicide among primary affective disorders. British Journal of Psychiatry 117: 437–438, 1970

    PubMed  Article  CAS  Google Scholar 

  • Hamilton M. The assessment of anxiety states by rating. British Journal of Medical Psychology 32: 50–55, 1959

    PubMed  Article  CAS  Google Scholar 

  • Hamilton M. A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23: 46–62, 1960

    Article  Google Scholar 

  • Hamilton M. Comparative value of rating scales. British Journal of Clinical Pharmacology 3 (Suppl.): 58–60, 1976

    PubMed  Article  CAS  Google Scholar 

  • Himmelhoch JM, Schechtman K, Auchenback R. The role of trazodone in the treatment of depressed cardiac patients. Psychopathology 17 (Suppl. 2): 51–63, 1984

    PubMed  Article  Google Scholar 

  • Hollister LE. Current antidepressant drugs: their clinical use. Drugs 22: 129–152, 1981

    PubMed  Article  CAS  Google Scholar 

  • Jabbari B, Bryan G, Mars LEE, Gunderson CH. Incidence of seizure with tricyclic and tetracyclic antidepressants. Archives of Neurology 42: 480–481, 1985

    PubMed  Article  CAS  Google Scholar 

  • Janowsky D, Curtis G, Zisook S, et al. Ventricular arrhythmias possibly aggravated by trazodone. American Journal of Psychiatry 140: 796–797, 1983

    PubMed  CAS  Google Scholar 

  • Knudsen K, Heath A. Effects of self poisoning with maprotiline. British Medical Journal 288: 601–603, 1984

    PubMed  Article  CAS  Google Scholar 

  • Kronig MH, Roose SP, Walsh BT, et al. Blood pressure effects of phenelzine. Journal of Clinical Psychopharmacology 3: 307–308, 1983

    PubMed  Article  CAS  Google Scholar 

  • Lewis JA. Postmarketing surveillance: how many patients? Trends in Pharmacological Sciences 2: 93–94, 1981

    Article  Google Scholar 

  • Litovitz TL, Troutman WG. Amoxapine overdose: seizures and fatalities. Journal of the American Medical Association 250: 1069–1071, 1983

    PubMed  Article  CAS  Google Scholar 

  • Mendez MF, Cummings JL, Benson DF. Psychotropic drugs and epilepsy. Stress Medicine 2: 325–332, 1986

    Article  Google Scholar 

  • Moir DC, Crooks J, Cornwell WB, et al. Cardiotoxicity of amitriptyline. Lancet 2: 561–564, 1972

    PubMed  Article  CAS  Google Scholar 

  • Moir DC, Dingwall-Fordyce I, Weir RD. Medicines evaluation and monitoring group: a follow-up study of cardiac patients receiving amitriptyline. European Journal of Clinical Pharmacology 6: 98–101, 1973

    PubMed  Article  CAS  Google Scholar 

  • Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134: 382–389, 1979

    PubMed  Article  CAS  Google Scholar 

  • Morris JB, Beck AT. The efficacy of antidepressant drugs: a review of research (1958-1972). Archives of General Psychiatry 30: 667, 1974

    PubMed  Article  CAS  Google Scholar 

  • Murphy E. General management of depression in late life. Journal of Affective Disorders (Suppl. 1): S7-S10, 1985

  • Nilsson BS. Adverse reactions in connection with zimeldine treatment: a review. Acta Psychiatrica Scandinavica 308 (Suppl. 1): 115–119, 1983

    PubMed  CAS  Google Scholar 

  • Ofsti E. Citalopram — a specific 5-HT reuptake inhibitor — as an antidepressant drug: a phase II multicentre trial. Progressive Neuro-Psychopharmacology and Biological Psychiatry 6: 327–335, 1982

    Article  CAS  Google Scholar 

  • O’Sullivan K. Depression and its treatment in alcoholics: a review. Canadian Journal of Psychiatry 29: 379–384, 1984

    Google Scholar 

  • Overall JE. Efficacy of nomifensine in different depressive syndromes. Journal of Clinical Psychiatry 45 (4 Sec. 2): 85–88, 1984

    PubMed  CAS  Google Scholar 

  • Paykel ES, Mueller PS, De La Vesgne PM. Amitriptyline, weight gain and carbohydrate craving: a side-effect. British Journal of Psychiatry 123: 501–507, 1973

    PubMed  Article  CAS  Google Scholar 

  • Peabody CA, Whiteford HA, Hollister LE. Antidepressants and the elderly. Journal of the American Geriatrics Society 34: 869–874, 1986

    PubMed  CAS  Google Scholar 

  • Pentel PR, Benowitz NL. Tricyclic antidepressant poisoning: management of arrhythmias. Medical Toxicology 1: 101–121, 1986

    PubMed  CAS  Google Scholar 

  • Prescott LF, Highley MS. Drugs prescribed for self poisoners. British Medical Journal 290: 1633–1636, 1985

    PubMed  Article  CAS  Google Scholar 

  • Pugh R, Bell J, Cooper AJ, Dunstan S, Greedharry D, et al. Does lofepramine have fewer side effects than amitriptyline: results of a comparative trial. Journal of Affective Disorders 4: 355–363, 1982

    PubMed  Article  CAS  Google Scholar 

  • Rabkin JG, Quitkin FM, McGrath P, et al. Adverse reactions to monoamine oxidase inhibitors, part II: treatment correlates and clinical management. Journal of Clinical Psychopharmacology 5: 1–9, 1985

    Article  Google Scholar 

  • Rickels K, Weise CC, Csanalosi I, et al. Clomipiamine and amitriptyline in depressed outpatients: a controlled study. Psychopharmacologia 34: 361–376, 1974

    PubMed  Article  CAS  Google Scholar 

  • Roos JC. Cardiac effects of antidepressant drugs: a comparison of the tricyclic antidepressants and fluvoxamine. British Journal of Clinical Pharmacology 15: 439S–445S, 1983

    PubMed  Article  Google Scholar 

  • Scher M, Krieger JN, Juergens S. Trazodone and priapism. American Journal of Psychiatry 140: 1362–1363, 1983

    PubMed  CAS  Google Scholar 

  • Skegg K, Skegg DCG, Richards SM. Incidence of self poisoning in patients prescribed psychotropic drugs. British Medical Journal 286: 841–848, 1983

    PubMed  Article  CAS  Google Scholar 

  • Snaith RP, Taylor CM. Rating scales for depression and anxiety: a current perspective. British Journal of Clinical Pharmacology 19: 17S–20S, 1985

    PubMed  Article  Google Scholar 

  • Tyrer P. Drug treatment of psychiatric patients in general practice. British Medical Journal 2: 1008–1010, 1978

    PubMed  Article  CAS  Google Scholar 

  • Veith RC, Raskind M, Caldwell JH, et al. Cardiovascular effects of tricyclic antidepressants in depressed patients with chronic heart disease. New England Journal of Medicine 306: 954–959, 1982

    PubMed  Article  CAS  Google Scholar 

  • Vlay SC, Friedling S. Trazodone exacerbation of VT. American Heart Journal 106: 604, 1983

    PubMed  Article  CAS  Google Scholar 

  • Waite J, Grundy E, Arie T. A controlled trial of antidepressant medication in elderly in-patients. International Clinical Psychopharmacology 1: 113–126, 1986

    PubMed  Article  CAS  Google Scholar 

  • Wedin GP, Oderda G, Klein-Schwartz W, Gorman R. Relative toxicity of cyclic antidepressants. Annals of Emergency Medicine 14: 797–804, 1986

    Article  Google Scholar 

  • Zung W, Magill M, Moore J, George D. Recognition and treatment of depression in family practice. Journal of Clinical Psychiatry 44: 3–6, 1983

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Henry, J.A., Martin, A.J. The Risk-Benefit Assessment of Antidepressant Drugs. Med Toxicol Adverse Drug Exp 2, 445–462 (1987). https://doi.org/10.1007/BF03259878

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259878

Keywords

  • Amitriptyline
  • Antidepressant Drug
  • Trazodone
  • Hamilton Depression Rate Scale
  • Mianserin