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Randomized Controlled Trial
. 2014 Dec;205(6):443-9.
doi: 10.1192/bjp.bp.113.140343. Epub 2014 Sep 11.

Role of pill-taking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression

Andrew F Leuchter  1 , Aimee M Hunter  1 , Molly Tartter  1 , Ian A Cook  1
Affiliations
Randomized Controlled Trial

Role of pill-taking, expectation and therapeutic alliance in the placebo response in clinical trials for major depression

Andrew F Leuchter et al. Br J Psychiatry. 2014 Dec.

Abstract

Background: Pill-taking, expectations and therapeutic alliance may account for much of the benefit of medication and placebo treatment for major depressive disorder (MDD). Aims To examine the effects of medication, placebo and supportive care on treatment outcome, and the relationships of expectations and therapeutic alliance to improvement.

Method: A total of 88 participants were randomised to 8 weeks of treatment with supportive care alone or combined with double-blind treatment with placebo or antidepressant medication. Expectations of medication effectiveness, general treatment effectiveness and therapeutic alliance were measured (trial registration at ClinicalTrials.gov: NCT00200902).

Results: Medication or placebo plus supportive care were not significantly different but had significantly better outcome than supportive care alone. Therapeutic alliance predicted response to medication and placebo; expectations of medication effectiveness at enrolment predicted only placebo response.

Conclusions: Pill treatment yielded better outcome than supportive care alone. Medication expectations uniquely predicted placebo treatment outcome and were formed by time of enrolment, suggesting that they were shaped by prior experiences outside the clinical trial.

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Conflict of interest statement

Declaration of interest

A.F.L, within the past 5 years, has received research support from the National Institutes of Health, Wyeth Pharmaceuticals, Novartis Pharmaceuticals, Seaside Therapeutics, Genentech, Shire Pharmaceuticals, Neuronetics, Eli Lilly and Company, and Neurosigma. He has served as a consultant to NeoSync Inc., Brain Cells, Inc., Taisho Pharmaceuticals, Eli Lilly and Company, and Aspect Medical Systems/Covidien. He is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA). He owns stock options in NeoSync, Inc. and has equity interest in BBA. I.A.C., within the past 5 years, has received research support from Aspect Medical Systems/Covidien, National Institutes of Health, Neuronetics and Shire; he has been on the speakers’ bureau for Neuronetics and the Medical Education Speakers Network; he has been an advisor/consultant/reviewer for Allergan, Covidien, Pfizer, Neuronetics, NeuroSigma, NIH (ITVS), US Department of Defense, US Department of Justice, VA (DSMB); his biomedical intellectual property is assigned to the Regents of the University of California, and he owns stock options in NeuroSigma.

Figures

Fig. 1
Fig. 1
CONSORT diagram.
Fig. 2
Fig. 2
Change in 17-item Hamilton Rating Scale for Depression (HRSD) scores during the study shown separately for each treatment group. Each point represents change from baseline HRSD at each study visit, as predicted by treatment condition, time, and the interaction of treatment condition and time, while covarying for baseline HRSD score.
Fig. 3
Fig. 3
Relationship between expectation and percentage change in 17-item Hamilton Rating Scale for Depression (HRSD) by treatment assignment (antidepressant medication or placebo). Open circles indicate participants in the placebo group, with the dotted regression line showing the relationship between expectations prior to treatment and reduction in depressive symptoms during the 8-week study (R2(linear) = 2.704E-4). Solid dots indicate participants in the medication group, with the solid regression line showing the relationship between expectations prior to treatment and symptom reduction over the 8-week study (R2(linear) = 0.213).
See this image and copyright information in PMC

Comment in

References

    1. Khan A, Fawcett J, Lichtenberg P, Kirsch I, Brown WA. A systematic review of comparative efficacy of treatments and controls for depression. PLoS One 2012; 7: e41778. - PMC - PubMed
    1. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008; 5: e45. - PMC - PubMed
    1. Khan A, Redding N, Brown WA. The persistence of the placebo response in antidepressant clinical trials. J Psychiatr Res 2008; 42: 791–6. - PubMed
    1. Khan A, Bhat A, Kolts R, Thase ME, Brown W. Why has the antidepressant-placebo difference in antidepressant clinical trials diminished over the past three decades? CNS Neurosci Ther 2010; 16: 217–26. - PMC - PubMed
    1. Walsh BT, Seidman SN, Sysko R, Gould M. Placebo response in studies of major depression: variable, substantial and growing. JAMA 2002; 287: 1840–7. - PubMed

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