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Antidepressant study design affects patient expectancy: a pilot study

Published online by Cambridge University Press:  07 September 2009

B. Rutherford ,
J. Sneed ,
D. Devanand ,
R. Eisenstadt  and
S. Roose
B. Rutherford*
Affiliation:
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA
J. Sneed
Affiliation:
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA
D. Devanand
Affiliation:
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA
R. Eisenstadt
Affiliation:
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA
S. Roose
Affiliation:
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA
*
*Address for correspondence: B. Rutherford, M.D., 1051 Riverside Dr., Box 98, New York, NY10032, USA. (Email: brr8@columbia.edu)
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Abstract

Background

Response to antidepressant medication is higher in comparator versus placebo-controlled randomized controlled trials (RCTs). Patient expectancy is an important influence on clinical outcome in the treatment of depression and may explain this finding. The results are reported from a pilot RCT studying expectancy and depression outcome in placebo-controlled versus comparator treatment conditions.

Method

Out-patients aged 18–65 years with major depressive disorder (MDD) were enrolled in this 8-week RCT. Subjects were randomized to placebo-controlled (escitalopram or placebo) or comparator (escitalopram or citalopram) administration of antidepressant medication. Subjects reported their expected likelihood and magnitude of depression improvement before and after randomization using questions from the Credibility and Expectancy Scale (CES). A regressed change model of post-randomization expectancy of improvement was fit to the data to determine whether subjects in the comparator group reported greater expectancies of improvement than subjects in the placebo-controlled group.

Results

Twenty subjects with mean age 56.5±11.7 years, a baseline Hamilton Depression Rating Scale (HAMD) score of 24.2±5.3, baseline Beck Depression Inventory (BDI) score of 24.9±6.4 and baseline Clinical Global Impressions (CGI) – Severity score of 4.0±0.3 were enrolled in the study. Adjusting for other factors, the effect of group assignment on expected magnitude of improvement was significant and large (effect size 1.5). No group differences in expected likelihood of improvement were found.

Conclusions

Randomization to comparator versus placebo-controlled administration of antidepressant medication produced greater expectancies of how much patients would improve during the trial. This expectancy difference may explain the higher response and remission rates that are observed in comparator versus placebo-controlled trials.

Keywords

Clinical trial designcomparatordepressionpatient expectancyplacebo-controlledplacebo effect
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 5 , May 2010 , pp. 781 - 788
Copyright
Copyright © Cambridge University Press 2009

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References

Beck, AT, Ward, CH, Mendelson, M (1961). An inventory of measuring depression. Archives of General Psychiatry 4, 53–63.CrossRefGoogle ScholarPubMed
Benedetti, F, Maggi, G, Lopiano, L, Lanotte, M, Rainero, I, Vighetti, S, Pollo, A (2003). Open versus hidden medical treatments: the patient's knowledge about a therapy affects the therapy outcome. Prevention and Treatment 6 (http://journals.apa.org/journals/pre/6/1/1a.html).CrossRefGoogle Scholar
Borkovec, TD, Costello, E (1993). Efficacy of applied relaxation and cognitive-behavioral therapy in the treatment of generalized anxiety disorder. Journal of Consulting and Clinical Psychology 61, 611–619.CrossRefGoogle ScholarPubMed
Borkovec, TD, Nau, SD (1972). Credibility of analogue therapy rationales. Journal of Behavioral Therapy and Experimental Psychiatry 3, 257–260.CrossRefGoogle Scholar
Cohen, J, Cohen, P, West, SG, Aiken, LS (2003). Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences, 3rd edn. Lawrence Erlbaum Associates: New York.Google Scholar
Devilly, GJ, Borkovec, TD (2000). Psychometric properties of the credibility/expectancy questionnaire. Journal of Behavioral Therapy and Experimental Psychiatry 31, 73–86.CrossRefGoogle ScholarPubMed
Guy, W (1976). Clinical Global Impressions. New Clinical Drug Evaluation Unit (ECDEU) Assessment Manual for Psychopharmacology, pp. 218–222. National Institute of Mental Health: Rockville, MD.Google Scholar
Hamilton, MW (1960). A rating scale for depression. Journal of Neurology and Neurosurgical Psychiatry 23, 56–60.CrossRefGoogle ScholarPubMed
Haour, F (2005). Mechanisms of the placebo effect and of conditioning. Neuroimmunomodulation 12, 195–200.CrossRefGoogle ScholarPubMed
Jiang, W, Krishnan, RR, O'Connor, CM (2002). Depression and heart disease: evidence of a link, and its therapeutic implications. CNS Drugs 16, 111–127.CrossRefGoogle ScholarPubMed
Kemeny, ME, Rosenwasser, LJ, Panettieri, RA, Rose, R, Berg-Smith, S, Kline, J (2007). Placebo response in asthma: a robust and objective phenomenon. Journal of Allergy and Clinical Immunology 119, 1375–1381.CrossRefGoogle ScholarPubMed
Kennedy, N, Paykel, ES (2004). Residual symptoms at remission from depression: impact on long-term outcome. Journal of Affective Disorders 80, 135–144.CrossRefGoogle ScholarPubMed
Kessler, RC, Berglund, P, Demler, O, Jin, R, Koretz, D, Merikangas, KR, Rush, AJ, Walters, EE, Wang, PS (2003). The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). Journal of the American Medical Association 289, 3095–3105.CrossRefGoogle ScholarPubMed
Kessler, RC, Chiu, WT, Demler, O, Walters, EE (2005). Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry 62, 617–627.CrossRefGoogle Scholar
Kirsch, I (1997). Specifying nonspecifics: psychological mechanisms of placebo effects. In The Placebo Effect: An Interdisciplinary Exploration (ed. Harrington, A.), pp. 166–183. Harvard University Press: Cambridge, MA.Google Scholar
Kirsch, I, Deacon, BJ, Huedo-Medina, TB, Scorboria, A, Moore, TJ, Johnson, BT (2008). Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. Public Library of Science Medicine 5, 260–268.Google ScholarPubMed
Kirsch, I, Sapirstein, G (1998). Listening to prozac but hearing placebo: a meta-analysis of antidepressant medication. Prevention and Treatment 1 (http://journals.apa.org/prevention/volumeI/pre0010002a.html).CrossRefGoogle Scholar
Krell, HV, Leuchter, AF, Morgan, M, Cook, IA, Abrams, M (2004). Subject expectations of treatment effectiveness and outcome of treatment with an experimental antidepressant. Journal of Clinical Psychiatry 65, 1174–1179.CrossRefGoogle ScholarPubMed
Lick, J, Bootzin, R (1975). Expectancy factors in the treatment of fear: methodological and theoretical issues. Psychological Bulletin 82, 917–931.CrossRefGoogle ScholarPubMed
Marmar, C, Gaston, L (1998). The California Pharmacotherapy Alliance Scale. Unpublished manual.Google Scholar
Noble, LM, Douglas, BC, Newman, SP (2001). What do patients expect of psychiatric services? A systematic and critical review of empirical studies. Social Science and Medicine 52, 985–998.CrossRefGoogle ScholarPubMed
Paykel, ES, Ramana, R, Cooper, Z, Hayhurst, H, Kerr, J, Barocka, A (1995). Residual symptoms after partial remission: an important outcome in depression. Psychological Medicine 25, 1171–1180.CrossRefGoogle ScholarPubMed
Pollo, A, Torre, E, Lopiano, L, Rizzone, M, Lanotte, M, Cavanna, A, Bergamasco, B, Benedetti, F (2002). Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients. NeuroReport 13, 1383–1386.CrossRefGoogle ScholarPubMed
Rush, AJ, Trivedi, MH, Wisniewski, SR, Nierenberg, AA, Stewart, JW, Warden, D, Niederehe, G, Thase, ME, Lavori, PW, Lebowitz, BD, McGrath, PJ, Rosenbaum, JF, Sackeim, HA, Kupfer, DJ, Luther, J, Fava, M (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry 163, 1905–1917.CrossRefGoogle ScholarPubMed
Rutherford, BR, Sneed, JR, Roose, SP (2009). Does study design affect outcome? The effects of placebo control and treatment duration in antidepressant trials. Psychotherapy and Psychosomatics 78, 172–181.CrossRefGoogle ScholarPubMed
Sneed, JR, Rutherford, BR, Rindskopf, D, Roose, SP (2008). Design makes a difference: antidepressant response rates in placebo-controlled versus comparator trials in late life depression. American Journal of Geriatric Psychiatry 16, 65–73.CrossRefGoogle ScholarPubMed
Sotsky, AM, Glass, DR, Shea, MT, Pilkonis, PA, Collins, F, Elkin, I, Watkins, JT, Imber, SD, Leber, WR, Moyer, J, Oliveri, ME (1991). Patient predictors of response to psychotherapy and pharmacotherapy: findings in the NIMH Treatment of Depression Collaborative Research Program. American Journal of Psychiatry 148, 997–1008.Google ScholarPubMed
Ventura, J, Liberman, RP, Green, MF, Shaner, A, Mintz, J (1998). Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-I/P). Psychiatry Research 79, 163–173.CrossRefGoogle ScholarPubMed
Walsh, BT, Seidman, SN, Sysko, R, Gould, M (2002). Placebo response in studies of major depression: variable, substantial, and growing. Journal of the American Medical Association 287, 1840–1847.CrossRefGoogle ScholarPubMed
Wilkins, W (1973). Expectancy of therapeutic gain: an empirical and conceptual critique. Journal of Consulting and Clinical Psychology 40, 69–77.CrossRefGoogle ScholarPubMed
WHO (2004). The World Health Report 2004: Changing History, Annex Table 3: Burden of disease in DALYs by cause, sex, and mortality stratum in WHO regions, estimates for 2002. World Health Organization: Geneva.Google Scholar