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Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders.

Publication ,  Journal Article
Cohen, EA; Hassman, HH; Ereshefsky, L; Walling, DP; Grindell, VM; Keefe, RSE; Wyka, K; Horan, WP
Published in: Neuropsychopharmacology
March 2021

The remarkably high and growing placebo response rates in clinical trials for CNS indications, such as depression and schizophrenia, constitute a major challenge for the drug development enterprise. Despite extensive literature on participant expectancies and other potent psychosocial factors that perpetuate placebo response, no empirically validated participant-focused strategies to mitigate this phenomenon have been available. This study evaluated the efficacy of the Placebo-Control Reminder Script (PCRS), a brief interactive procedure that educates participants about factors known to cause placebo response, which was administered prior to the primary outcome assessments to subjects with major depressive or psychotic disorders who had at least moderate depression. Participants were informed they would participate in a 2-week randomized clinical trial with a 50% chance of receiving either an experimental antidepressant medication or placebo. In actuality, all participants received placebo. Participants randomly assigned to receive the PCRS (n = 70) reported significantly smaller reductions (i.e., less placebo response) in depression than those who did not receive the PCRS (n = 67). The magnitude of this effect was medium (Cohen's d = 0.40) and was not significantly impacted by diagnostic status. The number of adverse events (i.e., nocebo effect) was also lower in the PCRS group, particularly in the first week of the study. These findings suggest that briefly educating participants about placebo response factors can help mitigate the large placebo response rates that are increasingly seen in failed CNS drug development programs.

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Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

March 2021

Volume

46

Issue

4

Start / End Page

844 / 850

Location

England

Related Subject Headings

  • Treatment Outcome
  • Single-Blind Method
  • Psychotic Disorders
  • Psychiatry
  • Placebo Effect
  • Humans
  • Double-Blind Method
  • Depressive Disorder, Major
  • Antidepressive Agents
  • 5202 Biological psychology
 

Citation

APA
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Cohen, E. A., Hassman, H. H., Ereshefsky, L., Walling, D. P., Grindell, V. M., Keefe, R. S. E., … Horan, W. P. (2021). Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders. Neuropsychopharmacology, 46(4), 844–850. https://doi.org/10.1038/s41386-020-00911-5
Cohen, Elan A., Howard H. Hassman, Larry Ereshefsky, David P. Walling, Vera M. Grindell, Richard S. E. Keefe, Katarzyna Wyka, and William P. Horan. “Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders.Neuropsychopharmacology 46, no. 4 (March 2021): 844–50. https://doi.org/10.1038/s41386-020-00911-5.
Cohen EA, Hassman HH, Ereshefsky L, Walling DP, Grindell VM, Keefe RSE, et al. Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders. Neuropsychopharmacology. 2021 Mar;46(4):844–50.
Cohen, Elan A., et al. “Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders.Neuropsychopharmacology, vol. 46, no. 4, Mar. 2021, pp. 844–50. Pubmed, doi:10.1038/s41386-020-00911-5.
Cohen EA, Hassman HH, Ereshefsky L, Walling DP, Grindell VM, Keefe RSE, Wyka K, Horan WP. Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders. Neuropsychopharmacology. 2021 Mar;46(4):844–850.

Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

March 2021

Volume

46

Issue

4

Start / End Page

844 / 850

Location

England

Related Subject Headings

  • Treatment Outcome
  • Single-Blind Method
  • Psychotic Disorders
  • Psychiatry
  • Placebo Effect
  • Humans
  • Double-Blind Method
  • Depressive Disorder, Major
  • Antidepressive Agents
  • 5202 Biological psychology