Skip to main content
SpringerLink
Log in

Role of the Placebo Response in the Treatment of Depressive Disorders

  • Leading Article
  • Published:
CNS Drugs Aims and scope Submit manuscript

Summary

Results from placebo-controlled trials of antidepressants have demonstrated that a large proportion of depressed patients show a significant improvement of symptoms while receiving placebo. In some patients, the improvement may be due to the natural course of the illness, independent of any therapeutic intervention, but in others it may be due to nonspecific therapeutic factors. Presumably, the latter are at least as relevant in clinical practice as in the research setting.

The factors responsible for the placebo effect are unknown. However, several clinical variables are associated with an improvement in depressed patients who receive placebo. The most consistent correlation is a negative one between the duration of the presenting episode and a diminished placebo response. In addition, the role of expectation or hope has been emphasised.

The placebo response appears to be less stable than the improvement attributable to drugs. In controlled antidepressant trials, a significant proportion of placebo responders will relapse during follow-up. Two patterns of placebo response have been identified; one is characterised by an early, abrupt, nonsustained improvement and the other by a gradual sustained response. The instability of the placebo response may explain why some patients lose an initial apparent antidepressant response.

It was recently proposed that the initial treatment for a sizeable proportion of depressed patients should be 4 to 6 weeks of placebo. This has been rejected on practical grounds. Although placebo treatment of depression cannot be fully advocated, knowledge of the determinants and course of the placebo response can be used to guide clinical management.

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

Access this article

Log in via an institution

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

  1. Brown WA. Placebo as a treatment for depression. Neuropsycho-pharmacology 1994; 10: 265–9

    CAS  Google Scholar 

  2. Shapiro AK. A historic and heuristic definition of the placebo. Psychiatry 1964; 27: 52–8

    PubMed  CAS  Google Scholar 

  3. Horace B. English, Ava Champney English. A comprehensive dictionary of psychological and analytical terms. New York: Longmans Green, 1958

    Google Scholar 

  4. Shapiro AK, Shapiro E. The placebo effect: art or science? Med Times 1982; Jun: 45s-52s

  5. Honigfeld G. Non-specific factors in treatment. I Review of placebo reactions and placebo reactors. Dis Nerv Sys 1964; 25: 145–56

    CAS  Google Scholar 

  6. Ross S, Buckelew LW. Placebo agentry: assessment of drug and placebo effects. In: White L, Tursky B, Schwartz GE, editors. Placebo theory, research, and mechanisms. New York: The Guildford Press, 1985: 67–82

    Google Scholar 

  7. Fisher S. Nonspecific factors as determinants of behavioral response to drugs. In: DiMascio A, Shader RI, editors. Clinical handbook of psychopharmacology. New York: Science House, 1970: 17–39

    Google Scholar 

  8. Grunbaum A. Explication and implications of the placebo concept. In: White L, Tursky B, Schwartz GE, editors. Placebo theory, research, and mechanisms. New York: The Guildford Press, 1985: 9–36

    Google Scholar 

  9. Hahn RA. A sociocultural model of illness and healing. In: White L, Tursky B, Schwartz GE, editors. Placebo theory, research, and mechanisms. New York: The Guildford Press, 1985: 167–95

    Google Scholar 

  10. Levine JD, Gordon NC, Fields HL. The mechanism of placebo analgesia. Lancet 1978; 2: 654–7

    Article  PubMed  CAS  Google Scholar 

  11. Shapiro AK, Morris LA. The placebo effect in medical and psychological psychotherapies. In: Garfield SL, Bergin AE, editors. Handbook of psychotherapy and behavior change. New York: Wiley, 1978: 369–410

    Google Scholar 

  12. Frank JD, Frank JB. Persuasion and healing: a comparative study of psychotherapy. London: The Johns Hopkins University Press, 1991

    Google Scholar 

  13. Khan A, Dager S, Cohen S, et al. Chronicity of depressive episode in relation to antidepressant-placebo response. Neuro-psychopharmacology 1991; 4: 125–30

    CAS  Google Scholar 

  14. Buckalew LW, Ross S, Starr BJ. Nonspecific factors in drug effects: placebo personality. Psychol Rep 1981; 48: 3–8

    Article  PubMed  CAS  Google Scholar 

  15. Fairchild CJ, Rush J, Nishendu V, et al. Which depressions respond to placebo?. Psychiatry Res 1986; 18: 217–26

    Article  PubMed  CAS  Google Scholar 

  16. Stewart JW, Quitkin FM, Liebowitz MR, et al. Efficacy of desipramine in depressed outpatients. Arch Gen Psychiatry 1983; 40: 202–7

    Article  PubMed  CAS  Google Scholar 

  17. Stewart JW, McGrath PJ, Quitkin FM. Can mildly depressed out-patients with atypical depression benefit from anti-depressants?. Am J Psychiatry 1992; 149: 615–9

    PubMed  CAS  Google Scholar 

  18. Khan A, Brown WA. Who should receive antidepressants: suggestions from placebo treatment. Psychopharmacol Bull 1991; 27: 271–4

    PubMed  CAS  Google Scholar 

  19. Klerman GL, Cole JO. Clinical pharmacology of imipramine and related compounds. Pharmacol Rev 1965; 17: 101–41

    PubMed  CAS  Google Scholar 

  20. Downing RW, Rickeis K. Predictors of response to amitripty-line in three outpatient treatment settings. J Nerv Ment Dis 1973; 156: 109–29

    Article  PubMed  CAS  Google Scholar 

  21. Rabkin JG, Stewart JW, McGrath PJ, et al. Baseline characteristics of 10-day washout responders in antidepressant trials. Psychiatry Res 1987; 21: 9–22

    Article  PubMed  CAS  Google Scholar 

  22. Brown WA, Dornseif BE, Wernicke JF. Placebo response in depression: a search for predictors. Psychiatry Res 1989; 26: 259–64

    Article  Google Scholar 

  23. Kocsis JH, Frances AJ, Voss C, et al. Imipramine treatment for chronic depression. Arch Gen Psychiatry 1988; 45: 253–7

    Article  PubMed  CAS  Google Scholar 

  24. Brown WA, Johnson MF, Chen M. Clinical features of depressed patients who do and do not improve with placebo. Psychiatry Res 1992; 41: 203–14

    Article  PubMed  CAS  Google Scholar 

  25. Wilcox CS, Cohn JB, Linden RD, et al. Predictors of placebo response: a retrospective analysis. Psychopharmacol Bull 1992; 28: 157–62

    PubMed  CAS  Google Scholar 

  26. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. American Psychiatric Association, 1980

  27. Klein DF. Identified placebo treatment?. Neuropsychopharma-cology 1994; 10: 271–2

    Google Scholar 

  28. Shrivastava RK, Schwimmer R, Brown WA, et al. DST predicts poor placebo response in depression [new research abstract no. 94]. Scientific Proceedings of the 138th meeting of the American Psychiatric Association; 1985 May 18–24: Dallas

  29. Brown WA, Shrivastava RK, Arato M. Pretreatment pituitary adrenocortical status and placebo response in depression. Psychopharmacol Bull 1987; 23: 155–9

    PubMed  CAS  Google Scholar 

  30. Preskorn SH, Weller EB, Hughes CW, et al. Depression in prepubertal children: dexamethasone nonsuppression predicts differential response vs placebo. Psychopharmacol Bull 1987; 23: 128–33

    PubMed  CAS  Google Scholar 

  31. Peselow ED, Stanley M, Fieve RR. Plasma Cortisol and clinical response to antidepressants and placebo in depressed outpatients. Scientific Proceedings of the American College of Neuro-psychopharmacology; 1985 Dec 9–13: Maui, Hawaii, 124

    Google Scholar 

  32. Peselow ED, Lautin A, Wolkin A, et al. The dexamethasone suppression test and response to placebo. J Clin Psychopharmacol 1986; 6: 286–91

    Article  PubMed  CAS  Google Scholar 

  33. Quitkin FM, McGrath PJ, Rabkin JG, et al. Different types of placebo in patients receiving antidepressants. Am J Psychiatry 1991; 148: 197–203

    PubMed  CAS  Google Scholar 

  34. Quitkin FM, Stewart JW, McGrath PJ, et al. Loss of effects during continuation therapy. Am J Psychiatry 1993; 150: 562–5

    PubMed  CAS  Google Scholar 

  35. Rabkin J, McGrath P, Stewart JW, et al. Follow-up of patients who improved during placebo washout. J Clin Psychopharmacol 1986; 6: 274–8

    Article  PubMed  CAS  Google Scholar 

  36. Dunner DL. Commentary on ‘placebo as a treatment for depression’. Neuropsychopharmacology 1994; 10: 273–4

    Google Scholar 

  37. Rush AJ. Placebo responsiveness does not imply that placebo is sufficient treatment. Neuropsychopharmacology 1994; 10: 281–3

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Depression Evaluation Service, New York State Psychiatric Institute, 722 West 168th Street, New York, New York, 10032, USA

    Pedro Luis Dago & Frederic M. Quitkin

Authors
  1. Pedro Luis Dago
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frederic M. Quitkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dago, P.L., Quitkin, F.M. Role of the Placebo Response in the Treatment of Depressive Disorders. CNS Drugs 4, 335–340 (1995). https://doi.org/10.2165/00023210-199504050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199504050-00002

Keywords

Search

Navigation