Skip to main content Accessibility help
×
Home

Placebo run-in period in studies of depressive disorders: Clinical, heuristic and research implications

  • Frederic M. Quitkin (a1), Patrick J. McGrath (a1), Jonathan W. Stewart (a1), Katja Ocepek-Welikson (a1), Bonnie P. Taylor (a1), Edward Nunes (a1), Deborah Delivannides (a1), Vito Agosti (a1), Steven J. Donovan (a1), Donald Ross (a1), Eva Petkova (a1) and Donald F. Klein (a1)...

Abstract

Background

In spite of the virtually ubiquitous nature of the initial 10-day placebo run-in period (IPR) in drug trials, there is little empirical data establishing its relevance.

Method

Data from 593 subjects were examined retrospectively to determine whether or not the prognosis of subjects minimally improved during the IPR was different to those who were unimproved. The IPR period was single-blind and was followed by a six-week double-blind phase in all studies.

Results

Twenty-six per cent of the subjects were minimally improved and 74% were unimproved. Approximately 10% of the subjects who were much improved were not followed systematically. Across a range of diagnosis, severity and chronicity subjects minimally improved (versus unimproved) after IPR had a more favourable prognosis whether assigned to drug or placebo.

Conclusions

Change during IPR appears to be a meaningful predictor. Stratification should be considered in future antidepressant studies.

Copyright

Corresponding author

Frederic Quitkin, 722 West 168th Street, Box 12, New York, NY 10032, USA

References

Hide All
Ainslie, J. D. Jones, M. B. & Stiefel, J. R. (1965) Practical drug evaluation method. Archives of General Psychiatry, 12, 368373.
Alexander, F. & French, T. M. (1946) Psychoanalytic Therapy. New York: Ronald Press.
American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III). Washington, DC: APA.
Alexander, F. (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.
Bieiski, R. J. & Friedel, R. O. (1976) Prediction of tricyclic antidepressant response. Archives of General Psychiatry, 33, 14791489.
Brown, W. A. Durnseif, B. E. & Wernicke, J. F. (1988) Placebo response in depression: a search for predictors. Psychiatry Research, 26, 259264.
Derogatis, L. R. Lipman, R. S. Rickels, K. et al (1974) The Hopkins symptom checklist (HSCL): a self-report symptom inventory. Behavioral Science, 19, 115.
Fleiss, J. L. (1986) The Design and Analysis of Clinical Experiments. New York: Wiley & Sons Inc.
Friedman, L. M. Furberg, C. D. & Demets, K. L. (1985) Fundamentals in Clinical Trials (2nd edn). Littleton, MA: PSG Publishing.
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology. Revised DHEW Pub. (ADM). Rockville, MD: National Institute for Mental Health.
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278296.
Joyce, P. R. & Paykel, E. D. (1989) Predictors of drug response in depression. Archives of General Psychiatry, 46, 8889.
Klerman, G. L. Dimascio, A. Weissman, M. et al (1974) Treatment of depression by drugs and psychotherapy. American Journal of Psychiatry, 131, 186191.
McGrath, P. J. Quitkin, F. M. Stewart, J. W. et al (1981) An open clinical trial of mianserin. American Journal of Psychiatry, 138, 530532.
McGrath, P. J. Rabkin, J. G. Stewart, J. W. et al (1985) Placebo-controlled study of mianserin in depressed out-patients. Neuropsychobiotogy, 14, 128132.
Quitkin, F. M. Stewart, J. W. McGrath, P. J. et al (1993) Columbia atypical depression. A subgroup of depressives with better response to MAOI than to tricyclic antidepressants or placebo. British Journal of Psychiatry 163 (suppl. 21), 3034.
Rabkin, J. G. (1987) Baseline characteristics of 10-day placebo washout responder in antidepressant trials. Psychiatry Research, 21, 922.
Reimherr, F. W. Ward, M. F. & Byerley, W. R. (1989) The introductory placebo washout: a retrospective evaluation. Psychiatry Research, 30, 191199.
Spitzer, R. Endicott, J. & Robins, E. (1978) Research diagnostic criteria: rationale and reliability. Archives of General Psychiatry, 35, 773782.
Stassen, H. H. Angst, J. & Delini-Stula, A. (1994) Severity at baseline and onset of improvement in depression. Meta-analysis of imipramine and moclobemide versus placebo. European Psychiatry, 9, 129136.
Stewart, J. W. Quitkin, F. M. Fyer, A. et al (1980) Efficacy of desipramine in endogenmorphically depressed patients. Journal of Affective Disorders, 2, 165176.
Stewart, J. W. Quitkin, F. M. McGrath, P. J. et al (1981) Efficacy of desipramine in mildly depressed patients: a double-blind placebo-controlled trial. Psychopharmacology Bulletin, 17, 159161.
Stewart, J. W. McGrath, P. J. Quitkin, F. M. et al (1989) Relevance of DSM–III depressive subtype and chronicity of antidepressant efficacy in atypical depression: differential response to phenelzine, imipramine and placebo. Archives of General Psychiatry, 46, 10801087.
Stewart, J. W. McGrath, P. J. Rabkin, J. G. et al (1993) Atypical depression: a valid clinical entity? Psychiatric Clinics of North America, 16, 479495.
Trivedi, M. H. & Rush, J. (1994) Does a placebo run-in or a placebo treatment cell affect the efficacy of antidepressant medications? Neuropsychopharmacology, 11, 3342.

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Placebo run-in period in studies of depressive disorders: Clinical, heuristic and research implications

  • Frederic M. Quitkin (a1), Patrick J. McGrath (a1), Jonathan W. Stewart (a1), Katja Ocepek-Welikson (a1), Bonnie P. Taylor (a1), Edward Nunes (a1), Deborah Delivannides (a1), Vito Agosti (a1), Steven J. Donovan (a1), Donald Ross (a1), Eva Petkova (a1) and Donald F. Klein (a1)...
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *