Open-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early Evidence
Background: Open-label placebo (OLP) represents an intervention where patients knowingly receive inert treatments associated with clinical benefits. This approach has demonstrated efficacy across multiple medical conditions. Meanwhile, major depressive disorder (MDD) affects 280 million people world...
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2026
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| author | Janet Mercedes Arévalo-Ipanaqué Maria Letícia Gobo Silva Ricardo Romero-Vucovich Gianluca Conte Matheus Gerhard Rosenfeld Sergio José Fausto Girón Lisa Gonzalez Jordy Batista Sofia Ines Volpi Maximiliano Espinosa Daniela Lorena Alvarado Rodriguez Salvatore Minnella Tadeus Lopez Ulloa Nadine Aranis Seguic Yazmin Heredia Allegretti Johan Antonio De La Rosa Laureano Cristian Camilo Bermudez Letícia Watanabe Koyama Maria Eduarda Nabhan de Souza Somaya Althobaiti Karen Gamonal Folasade Mary Adeyemi Luis Pedro Lorenzana Aderibigbe Adeniyi Sheriff Peter Benedek Emilio Vilorio-Alvarez Wajih Jawhar |
| author_browse | Aderibigbe Adeniyi Sheriff Cristian Camilo Bermudez Daniela Lorena Alvarado Rodriguez Emilio Vilorio-Alvarez Folasade Mary Adeyemi Gianluca Conte Janet Mercedes Arévalo-Ipanaqué Johan Antonio De La Rosa Laureano Jordy Batista Karen Gamonal Letícia Watanabe Koyama Lisa Gonzalez Luis Pedro Lorenzana Maria Eduarda Nabhan de Souza Maria Letícia Gobo Silva Matheus Gerhard Rosenfeld Maximiliano Espinosa Nadine Aranis Seguic Peter Benedek Ricardo Romero-Vucovich Salvatore Minnella Sergio José Fausto Girón Sofia Ines Volpi Somaya Althobaiti Tadeus Lopez Ulloa Wajih Jawhar Yazmin Heredia Allegretti |
| author_facet | Janet Mercedes Arévalo-Ipanaqué Maria Letícia Gobo Silva Ricardo Romero-Vucovich Gianluca Conte Matheus Gerhard Rosenfeld Sergio José Fausto Girón Lisa Gonzalez Jordy Batista Sofia Ines Volpi Maximiliano Espinosa Daniela Lorena Alvarado Rodriguez Salvatore Minnella Tadeus Lopez Ulloa Nadine Aranis Seguic Yazmin Heredia Allegretti Johan Antonio De La Rosa Laureano Cristian Camilo Bermudez Letícia Watanabe Koyama Maria Eduarda Nabhan de Souza Somaya Althobaiti Karen Gamonal Folasade Mary Adeyemi Luis Pedro Lorenzana Aderibigbe Adeniyi Sheriff Peter Benedek Emilio Vilorio-Alvarez Wajih Jawhar |
| author_sort | Janet Mercedes Arévalo-Ipanaqué |
| collection | Producción científica |
| description | Background: Open-label placebo (OLP) represents an intervention where patients knowingly receive inert treatments associated with clinical benefits. This approach has demonstrated efficacy across multiple medical conditions. Meanwhile, major depressive disorder (MDD) affects 280 million people worldwide, yet three-quarters receive no treatment, urging non-pharmacological approaches. Despite this high prevalence, there is scarce data on the potential of OLP intervention for MDD. Our objective is to determine whether OLP can meaningfully reduce depression scores in adults with MDD. Methods: Following Cochrane methodology and PRISMA guidelines, six databases were systematically reviewed including studies from up to May 5, 2025. Inclusion criteria encompassed randomized controlled trials (RCTs) examining OLP interventions in adults with MDD, measuring depression severity using validated scales. Studies were independently screened by multiple reviewers. Risk of bias was assessed using RoB2. A meta-analysis was conducted using post-intervention mean scores and standard deviations. Results: From 1,886 screened records, 3 randomized controlled trials (n=118; mean age 46.8 years; 78% female) met the inclusion. Trials were conducted in the USA, Israel, and Austria between 2012 and 2022, with sample sizes ranging from 20–60 participants. All compared open-label placebo (OLP) to treatment-as-usual or waitlist controls, using validated depression scales (HAM-D-17, QIDS-SR, BDI-II). Individual trial findings were mixed: one trial found significant symptom reduction with OLP plus cognitive-behavioral therapy, though the effect was small; two trials reported no overall between-group differences, although one showed improvement in patients with early-onset depression. A meta-analysis of two small trials at 4 weeks suggested a modest reduction in depressive symptoms favoring OLP (Hedges's g=−0.43, 95% CI −0.83 to −0.04), although both individual trials were underpowered and did not reach statistical significance. Given the limited number of studies and high risk of bias, these findings should be interpreted as preliminary. Risk of bias was rated as some concerns in one study and high in two, primarily due to outcome measurement and missing data. Conclusions: Current evidence from three small RCTs suggests that open-label placebo may be associated with modest short-term symptom improvement in adults with MDD; however, the evidence base is limited, heterogeneous, and at risk of bias. These findings should be considered preliminary and hypothesis-generating, and larger, methodologically rigorous trials are required before clinical recommendations can be made. |
| format | Article |
| id | oai:cris.upeu.edu.pe:20.500.15037/882 |
| institution | UPeU |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| record_format | dspace |
| spelling | oai:cris.upeu.edu.pe:20.500.15037/8822026-10-30T16:14:56ZOpen-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early EvidenceJanet Mercedes Arévalo-IpanaquéMaria Letícia Gobo SilvaRicardo Romero-VucovichGianluca ConteMatheus Gerhard RosenfeldSergio José Fausto GirónLisa GonzalezJordy BatistaSofia Ines VolpiMaximiliano EspinosaDaniela Lorena Alvarado RodriguezSalvatore MinnellaTadeus Lopez UlloaNadine Aranis SeguicYazmin Heredia AllegrettiJohan Antonio De La Rosa LaureanoCristian Camilo BermudezLetícia Watanabe KoyamaMaria Eduarda Nabhan de SouzaSomaya AlthobaitiKaren GamonalFolasade Mary AdeyemiLuis Pedro LorenzanaAderibigbe Adeniyi SheriffPeter BenedekEmilio Vilorio-AlvarezWajih JawharPlaceboDepression (economics)MedicineRandomized controlled trialClinical trialPsychological interventionPlacebo responseDepressive symptomsMeta-analysisSample size determinationIntervention (counseling)Physical therapyMajor depressive disorderPsychiatryClinical psychologySystematic reviewMEDLINEStrictly standardized mean differenceInternal medicineResearch designSeverity of illnessHistory of depressionYoung adultRandomizationPlaceboDepression (economics)Randomized controlled trialClinical trialPsychological interventionPlacebo responseDepressive symptomsMeta-analysisLife Sciences Neuroscience Cognitive Neuroscience Pain Management and Placebo EffectHealth Sciences Medicine Pharmacology Treatment of Major DepressionSocial Sciences Decision Sciences Statistics, Probability and Uncertainty Meta-analysis and systematic reviewsBackground: Open-label placebo (OLP) represents an intervention where patients knowingly receive inert treatments associated with clinical benefits. This approach has demonstrated efficacy across multiple medical conditions. Meanwhile, major depressive disorder (MDD) affects 280 million people worldwide, yet three-quarters receive no treatment, urging non-pharmacological approaches. Despite this high prevalence, there is scarce data on the potential of OLP intervention for MDD. Our objective is to determine whether OLP can meaningfully reduce depression scores in adults with MDD. Methods: Following Cochrane methodology and PRISMA guidelines, six databases were systematically reviewed including studies from up to May 5, 2025. Inclusion criteria encompassed randomized controlled trials (RCTs) examining OLP interventions in adults with MDD, measuring depression severity using validated scales. Studies were independently screened by multiple reviewers. Risk of bias was assessed using RoB2. A meta-analysis was conducted using post-intervention mean scores and standard deviations. Results: From 1,886 screened records, 3 randomized controlled trials (n=118; mean age 46.8 years; 78% female) met the inclusion. Trials were conducted in the USA, Israel, and Austria between 2012 and 2022, with sample sizes ranging from 20–60 participants. All compared open-label placebo (OLP) to treatment-as-usual or waitlist controls, using validated depression scales (HAM-D-17, QIDS-SR, BDI-II). Individual trial findings were mixed: one trial found significant symptom reduction with OLP plus cognitive-behavioral therapy, though the effect was small; two trials reported no overall between-group differences, although one showed improvement in patients with early-onset depression. A meta-analysis of two small trials at 4 weeks suggested a modest reduction in depressive symptoms favoring OLP (Hedges's g=−0.43, 95% CI −0.83 to −0.04), although both individual trials were underpowered and did not reach statistical significance. Given the limited number of studies and high risk of bias, these findings should be interpreted as preliminary. Risk of bias was rated as some concerns in one study and high in two, primarily due to outcome measurement and missing data. Conclusions: Current evidence from three small RCTs suggests that open-label placebo may be associated with modest short-term symptom improvement in adults with MDD; however, the evidence base is limited, heterogeneous, and at risk of bias. These findings should be considered preliminary and hypothesis-generating, and larger, methodologically rigorous trials are required before clinical recommendations can be made.Articlehttps://doi.org/10.21801/ppcrj.2025.114.310.21801/ppcrj.2025.114.3https://hdl.handle.net/20.500.15037/882W7155631142Principles and Practice of Clinical Research Journal2378-18902026-04-262026-06-13T09:39:30Z2026-06-13T09:39:30Z |
| spellingShingle | Placebo Depression (economics) Medicine Randomized controlled trial Clinical trial Psychological intervention Placebo response Depressive symptoms Meta-analysis Sample size determination Intervention (counseling) Physical therapy Major depressive disorder Psychiatry Clinical psychology Systematic review MEDLINE Strictly standardized mean difference Internal medicine Research design Severity of illness History of depression Young adult Randomization Placebo Depression (economics) Randomized controlled trial Clinical trial Psychological intervention Placebo response Depressive symptoms Meta-analysis Life Sciences Neuroscience Cognitive Neuroscience Pain Management and Placebo Effect Health Sciences Medicine Pharmacology Treatment of Major Depression Social Sciences Decision Sciences Statistics, Probability and Uncertainty Meta-analysis and systematic reviews Janet Mercedes Arévalo-Ipanaqué Maria Letícia Gobo Silva Ricardo Romero-Vucovich Gianluca Conte Matheus Gerhard Rosenfeld Sergio José Fausto Girón Lisa Gonzalez Jordy Batista Sofia Ines Volpi Maximiliano Espinosa Daniela Lorena Alvarado Rodriguez Salvatore Minnella Tadeus Lopez Ulloa Nadine Aranis Seguic Yazmin Heredia Allegretti Johan Antonio De La Rosa Laureano Cristian Camilo Bermudez Letícia Watanabe Koyama Maria Eduarda Nabhan de Souza Somaya Althobaiti Karen Gamonal Folasade Mary Adeyemi Luis Pedro Lorenzana Aderibigbe Adeniyi Sheriff Peter Benedek Emilio Vilorio-Alvarez Wajih Jawhar Open-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early Evidence |
| title | Open-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early Evidence |
| title_full | Open-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early Evidence |
| title_fullStr | Open-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early Evidence |
| title_full_unstemmed | Open-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early Evidence |
| title_short | Open-Label Placebo Effects in Reducing Depression Severity Among Adults with Major Depressive Disorder: A Systematic Review and Meta-Analysis of Early Evidence |
| title_sort | open label placebo effects in reducing depression severity among adults with major depressive disorder a systematic review and meta analysis of early evidence |
| topic | Placebo Depression (economics) Medicine Randomized controlled trial Clinical trial Psychological intervention Placebo response Depressive symptoms Meta-analysis Sample size determination Intervention (counseling) Physical therapy Major depressive disorder Psychiatry Clinical psychology Systematic review MEDLINE Strictly standardized mean difference Internal medicine Research design Severity of illness History of depression Young adult Randomization Placebo Depression (economics) Randomized controlled trial Clinical trial Psychological intervention Placebo response Depressive symptoms Meta-analysis Life Sciences Neuroscience Cognitive Neuroscience Pain Management and Placebo Effect Health Sciences Medicine Pharmacology Treatment of Major Depression Social Sciences Decision Sciences Statistics, Probability and Uncertainty Meta-analysis and systematic reviews |
| topic_facet | Placebo Depression (economics) Medicine Randomized controlled trial Clinical trial Psychological intervention Placebo response Depressive symptoms Meta-analysis Sample size determination Intervention (counseling) Physical therapy Major depressive disorder Psychiatry Clinical psychology Systematic review MEDLINE Strictly standardized mean difference Internal medicine Research design Severity of illness History of depression Young adult Randomization Placebo Depression (economics) Randomized controlled trial Clinical trial Psychological intervention Placebo response Depressive symptoms Meta-analysis Life Sciences Neuroscience Cognitive Neuroscience Pain Management and Placebo Effect Health Sciences Medicine Pharmacology Treatment of Major Depression Social Sciences Decision Sciences Statistics, Probability and Uncertainty Meta-analysis and systematic reviews |
| url | https://doi.org/10.21801/ppcrj.2025.114.3 https://hdl.handle.net/20.500.15037/882 |
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