Skip to main content Accessibility help

A randomized, prospective pilot study of patient expectancy and antidepressant outcome

  • B. R. Rutherford (a1), S. M. Marcus (a2), P. Wang (a2), J. R. Sneed (a3), G. Pelton (a1), D. Devanand (a1), N. Duan (a2) and S. P. Roose (a1)...



This study is a randomized, prospective, investigation of the relationships between clinical trial design, patient expectancy and the outcome of treatment with antidepressant medication.


Adult out-patients with major depressive disorder (MDD) were randomized to either placebo-controlled (PC, 50% probability of receiving active medication) or comparator (COMP, 100% probability of receiving active medication) administration of antidepressant medication. Independent-samples t tests and analysis of covariance (ANCOVA) were used to determine whether the probability of receiving active medication influenced patient expectancy and to compare medication response in the PC v. COMP conditions. We also tested the correlations between baseline expectancy score and final improvement in depressive symptoms across study groups.


Subjects randomized to the COMP condition reported greater expectancy of improvement compared to subjects in the PC condition (t = 2.60, df = 27, p = 0.015). There were no statistically significant differences in the analyses comparing antidepressant outcomes between subjects receiving medication in the COMP condition and those receiving medication in the PC condition. Higher baseline expectancy of improvement was correlated with lower final depression severity scores (r = 0.53, p = 0.021) and greater improvement in depressive symptoms over the course of the study (r = 0.44, p = 0.058).


The methods described represent a promising way of subjecting patient expectancy to scientific study. Expectancy of improvement is affected by the probability of receiving active antidepressant medication and seems to influence antidepressant response.


Corresponding author

*Address for correspondence: Dr B. R. Rutherford, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. (Email:


Hide All
APA (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn, text revision (DSM-IV-TR). American Psychiatric Association: Washington, DC.
Auquier, P, Robitail, S, Llorca, PM, Rive, B (2003). Comparison of escitalopram and citalopram efficacy: a meta-analysis. International Journal of Psychiatry in Clinical Practice 7, 259268.
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory of measuring depression. Archives of General Psychiatry 4, 5363.
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, 611619.
Borkovec, TD, Nau, SD (1972). Credibility of analogue therapy rationales. Journal of Behavioral Therapy and Experimental Psychiatry 3, 257260.
Devilly, GJ, Borkovec, TD (2000). Psychometric properties of the credibility/expectancy questionnaire. Journal of Behavioral Therapy and Experimental Psychiatry 31, 7386.
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1996). Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press: Washington, DC.
Guy, W (1976). Clinical Global Impressions. New Clinical Drug Evaluation Unit (ECDEU) Assessment Manual for Psychopharmacology, pp. 218222. National Institute of Mental Health: Rockville, MD.
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Kirsch, I (1997). Specifying nonspecifics: psychological mechanisms of placebo effects. In The Placebo Effect: An Interdisciplinary Exploration (ed. Harrington, A.), pp. 166186. Harvard University Press: Cambridge, MA.
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, 11741179.
Meyer, B, Pilkonis, PA, Krupnick, JL, Egan, MK, Simmens, SJ, Sotsky, SM (2002). Treatment expectancies, patient alliance, and outcome: further analyses from the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Journal of Consulting and Clinical Psychology 70, 10511055.
Papakostas, GI, Fava, M (2009). Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD. European Neuropsychopharmacology 19, 3440.
Rutherford, BR, Sneed, JR, Eisenstadt, R, Roose, SP (2010 a). Antidepressant study design affects patient expectations: initial results from a randomized controlled trial. Psychological Medicine 40, 781788.
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, 172181.
Rutherford, BR, Sneed, JR, Tandler, J, Peterson, BS, Roose, SP (2011). Deconstructing pediatric depression trials: an analysis of the effects of expectancy and therapeutic contact. Journal of the American Academy of Child and Adolescent Psychiatry 50, 782795.
Rutherford, BR, Wager, TD, Roose, SP (2010 b). Expectancy effects in the treatment of depression: a review of experimental methodology, effects on patient outcome, and neural mechanisms. Current Reviews in Psychiatry 6, 110.
Sinyor, M, Levitt, AJ, Cheung, AH, Schaffer, A, Kiss, A, Dowlati, Y, Lanctot, KL (2010). Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses. Journal of Clinical Psychiatry 71, 270279.
Sneed, JR, Rutherford, BR, Rindskopf, D, Lane, DT, Sackeim, HA, Roose, SP (2008). Design makes a difference: a meta-analysis of antidepressant response rates in placebo-controlled versus comparator trials in late-life depression. American Journal of Geriatric Psychiatry 16, 6573.
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, 9971008.
Svensson, S, Mansfield, PR (2004). Escitalopram: superior to citalopram of chiral chimera? Psychotherapy and Psychosomatics 73, 1016.


A randomized, prospective pilot study of patient expectancy and antidepressant outcome

  • B. R. Rutherford (a1), S. M. Marcus (a2), P. Wang (a2), J. R. Sneed (a3), G. Pelton (a1), D. Devanand (a1), N. Duan (a2) and S. P. Roose (a1)...


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