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

  • Andrew F. Leuchter (a1), Aimee M. Hunter (a1), Molly Tartter (a2) and Ian A. Cook (a3)

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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Copyright

Corresponding author

Andrew F. Leuchter, MD, Laboratory of Brain, Behavior, and Pharmacology, Semel Institute for Neuroscience and Human Behavior at UCLA, 760 Westwood Plaza, Los Angeles, CA 90024, USA. Email: afl@ucla.edu

Footnotes

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Research support for this study was received from the National Center for Complementary and Alternative Medicine of the National Institutes of Health (grant number R01 AT002479), Eli Lilly and Company and Wyeth Pharmaceuticals (now a wholly owned subsidiary of Pfizer).

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.

Footnotes

References

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

  • Andrew F. Leuchter (a1), Aimee M. Hunter (a1), Molly Tartter (a2) and Ian A. Cook (a3)

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