Skip to main content Accessibility help
×
Home
Hostname: page-component-544b6db54f-lmg95 Total loading time: 0.255 Render date: 2021-10-22T11:10:10.912Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

Placebo run-in period in studies of depressive disorders

Clinical, heuristic and research implications

Published online by Cambridge University Press:  03 January 2018

Frederic M. Quitkin
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Patrick J. McGrath
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Jonathan W. Stewart
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Katja Ocepek-Welikson
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Bonnie P. Taylor
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Edward Nunes
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Deborah Delivannides
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Vito Agosti
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Steven J. Donovan
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Donald Ross
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Eva Petkova
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA
Donald F. Klein
Affiliation:
Department of Therapeutics, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institution, New York, USA

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.

Type
Papers
Copyright
Copyright © 1998 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ainslie, J. D. Jones, M. B. & Stiefel, J. R. (1965) Practical drug evaluation method. Archives of General Psychiatry, 12, 368373.CrossRefGoogle ScholarPubMed
Alexander, F. & French, T. M. (1946) Psychoanalytic Therapy. New York: Ronald Press.Google ScholarPubMed
American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (3rd edn) (DSM–III). Washington, DC: APA.Google ScholarPubMed
Alexander, F. (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM–III–R). Washington, DC: APA.Google Scholar
Bieiski, R. J. & Friedel, R. O. (1976) Prediction of tricyclic antidepressant response. Archives of General Psychiatry, 33, 14791489.CrossRefGoogle Scholar
Brown, W. A. Durnseif, B. E. & Wernicke, J. F. (1988) Placebo response in depression: a search for predictors. Psychiatry Research, 26, 259264.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Fleiss, J. L. (1986) The Design and Analysis of Clinical Experiments. New York: Wiley & Sons Inc. Google Scholar
Friedman, L. M. Furberg, C. D. & Demets, K. L. (1985) Fundamentals in Clinical Trials (2nd edn). Littleton, MA: PSG Publishing.Google Scholar
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology. Revised DHEW Pub. (ADM). Rockville, MD: National Institute for Mental Health.Google Scholar
Hamilton, M. (1967) Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology, 6, 278296.CrossRefGoogle ScholarPubMed
Joyce, P. R. & Paykel, E. D. (1989) Predictors of drug response in depression. Archives of General Psychiatry, 46, 8889.CrossRefGoogle ScholarPubMed
Klerman, G. L. Dimascio, A. Weissman, M. et al (1974) Treatment of depression by drugs and psychotherapy. American Journal of Psychiatry, 131, 186191.CrossRefGoogle Scholar
McGrath, P. J. Quitkin, F. M. Stewart, J. W. et al (1981) An open clinical trial of mianserin. American Journal of Psychiatry, 138, 530532.Google ScholarPubMed
McGrath, P. J. Rabkin, J. G. Stewart, J. W. et al (1985) Placebo-controlled study of mianserin in depressed out-patients. Neuropsychobiotogy, 14, 128132.CrossRefGoogle Scholar
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.Google Scholar
Rabkin, J. G. (1987) Baseline characteristics of 10-day placebo washout responder in antidepressant trials. Psychiatry Research, 21, 922.CrossRefGoogle Scholar
Reimherr, F. W. Ward, M. F. & Byerley, W. R. (1989) The introductory placebo washout: a retrospective evaluation. Psychiatry Research, 30, 191199.CrossRefGoogle ScholarPubMed
Spitzer, R. Endicott, J. & Robins, E. (1978) Research diagnostic criteria: rationale and reliability. Archives of General Psychiatry, 35, 773782.CrossRefGoogle ScholarPubMed
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.Google Scholar
Stewart, J. W. Quitkin, F. M. Fyer, A. et al (1980) Efficacy of desipramine in endogenmorphically depressed patients. Journal of Affective Disorders, 2, 165176.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
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.CrossRefGoogle Scholar
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.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.
25
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Placebo run-in period in studies of depressive disorders
Available formats
×

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

Placebo run-in period in studies of depressive disorders
Available formats
×

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

Placebo run-in period in studies of depressive disorders
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *