Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.

<h4>Background</h4>Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo...

Full description

Saved in:
Bibliographic Details
Main Authors: André Russowsky Brunoni, Mariana Lopes, Ted J Kaptchuk, Felipe Fregni
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0004824
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849706286492418048
author André Russowsky Brunoni
Mariana Lopes
Ted J Kaptchuk
Felipe Fregni
author_facet André Russowsky Brunoni
Mariana Lopes
Ted J Kaptchuk
Felipe Fregni
author_sort André Russowsky Brunoni
collection DOAJ
description <h4>Background</h4>Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device- rTMS) trials.<h4>Methodology/principal findings</h4>We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6) and rTMS studies (0.82; 95%C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized.<h4>Conclusions/significance</h4>We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself.
format Article
id doaj-art-1c4d2a0ff06947a8a5204276ca6927be
institution DOAJ
issn 1932-6203
language English
publishDate 2009-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-1c4d2a0ff06947a8a5204276ca6927be2025-08-20T03:16:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e482410.1371/journal.pone.0004824Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.André Russowsky BrunoniMariana LopesTed J KaptchukFelipe Fregni<h4>Background</h4>Although meta-analyses have shown that placebo responses are large in Major Depressive Disorder (MDD) trials; the placebo response of devices such as repetitive transcranial magnetic stimulation (rTMS) has not been systematically assessed. We proposed to assess placebo responses in two categories of MDD trials: pharmacological (antidepressant drugs) and non-pharmacological (device- rTMS) trials.<h4>Methodology/principal findings</h4>We performed a systematic review and meta-analysis of the literature from April 2002 to April 2008, searching MEDLINE, Cochrane, Scielo and CRISP electronic databases and reference lists from retrieved studies and conference abstracts. We used the keywords placebo and depression and escitalopram for pharmacological studies; and transcranial magnetic stimulation and depression and sham for non-pharmacological studies. All randomized, double-blinded, placebo-controlled, parallel articles on major depressive disorder were included. Forty-one studies met our inclusion criteria - 29 in the rTMS arm and 12 in the escitalopram arm. We extracted the mean and standard values of depression scores in the placebo group of each study. Then, we calculated the pooled effect size for escitalopram and rTMS arm separately, using Cohen's d as the measure of effect size. We found that placebo response are large for both escitalopram (Cohen's d - random-effects model - 1.48; 95%C.I. 1.26 to 1.6) and rTMS studies (0.82; 95%C.I. 0.63 to 1). Exploratory analyses show that sham response is associated with refractoriness and with the use of rTMS as an add-on therapy, but not with age, gender and sham method utilized.<h4>Conclusions/significance</h4>We confirmed that placebo response in MDD is large regardless of the intervention and is associated with depression refractoriness and treatment combination (add-on rTMS studies). The magnitude of the placebo response seems to be related with study population and study design rather than the intervention itself.https://doi.org/10.1371/journal.pone.0004824
spellingShingle André Russowsky Brunoni
Mariana Lopes
Ted J Kaptchuk
Felipe Fregni
Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.
PLoS ONE
title Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.
title_full Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.
title_fullStr Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.
title_full_unstemmed Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.
title_short Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis.
title_sort placebo response of non pharmacological and pharmacological trials in major depression a systematic review and meta analysis
url https://doi.org/10.1371/journal.pone.0004824
work_keys_str_mv AT andrerussowskybrunoni placeboresponseofnonpharmacologicalandpharmacologicaltrialsinmajordepressionasystematicreviewandmetaanalysis
AT marianalopes placeboresponseofnonpharmacologicalandpharmacologicaltrialsinmajordepressionasystematicreviewandmetaanalysis
AT tedjkaptchuk placeboresponseofnonpharmacologicalandpharmacologicaltrialsinmajordepressionasystematicreviewandmetaanalysis
AT felipefregni placeboresponseofnonpharmacologicalandpharmacologicaltrialsinmajordepressionasystematicreviewandmetaanalysis