Meta-analysis of the placebo response in antidepressant trials

Rief, Winfried; Nestoriuc, Yvonne; Weiss, Sarah; Welzel, Eva; Barsky, Arthur J.; Hofmann, S.

doi:10.1016/j.jad.2009.01.029

Cited by 267 publications

(204 citation statements)

References 32 publications

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…The placebo response was highest for depression as a primary outcome. However, there were also substantial placebo responses for secondary outcomes such as anxiety, general psychopathology and quality of life [13]. The results are in line with the findings from other meta-analyses and confirm the strong placebo response to antidepressant medication [2,4,7,[14][15][16].…”

Section: The Placebo Response In Antidepressant Trialssupporting

confidence: 87%

“…A meta-analysis by our group confirmed the large placebo response in antidepressant trials [13]. Moderator Table 1.…”

Section: Implications For Clinical Research and Practicementioning

confidence: 66%

“…Thus, the belief in the effectiveness of antidepressant medication has probably increased over the last decades. Indeed, positive expectations and confidence in the drug have increased for study investigators, but not for study participants [13]. However, alternative explanations involve changes in the study populations, such as sample homogeneity.…”

Section: Moderators Of the Placebo Responsementioning

confidence: 99%

See 2 more Smart Citations

Lessons learned from placebo groups in antidepressant trials

Shedden-Mora

Nestoriuc

Rief

2011

Phil. Trans. R. Soc. B

Self Cite

View full text Add to dashboard Cite

This comprehensive review provides an overview about placebo and nocebo phenomena in antidepressant trials. Improvements in the placebo groups may partly be explained through methodological issues such as natural course of depression and regression to the mean, but also fundamentally reflect investigators' and participants' expectations. A meta-analysis by our group of 96 randomized placebo-controlled trials showed large placebo responses to antidepressant medication. Moderator analyses revealed substantially larger placebo responses in observer ratings compared with self-report. Effect sizes in observer ratings showed strong increase with publication year while this effect was not found for patients' self-ratings. This reflects the strong influence of investigators' expectations. The analysis of 'nocebo effects', e.g. adverse effects in placebo groups of antidepressant trials also confirms the impact of expectations: nocebo symptoms reflected the typical side-effect patterns expected in the drug group, with higher symptoms rates in the placebo groups of tricyclic antidepressant trials compared with placebo groups of trials testing selective serotonin reuptake inhibitors. While the placebo response seems to be similar for women and men, gender differences were found for nocebo rates. In the conclusion, we discuss potential implications for clinical trial designs and argue for interventions aimed at optimizing positive expectations of treatment benefit while minimizing the impact of adverse effects.

show abstract

Section: The Placebo Response In Antidepressant Trialssupporting

confidence: 87%

“…A meta-analysis by our group confirmed the large placebo response in antidepressant trials [13]. Moderator Table 1.…”

Section: Implications For Clinical Research and Practicementioning

confidence: 66%

Section: Moderators Of the Placebo Responsementioning

confidence: 99%

See 1 more Smart Citation

Lessons learned from placebo groups in antidepressant trials

Shedden-Mora

Nestoriuc

Rief

2011

Phil. Trans. R. Soc. B

Self Cite

View full text Add to dashboard Cite

show abstract

“…Patients in pill placebo conditions are provided with positive expectations and considerable encouragement and support that may be sufficient to produce improvement (Rief et al 2009). In our meta-analysis we found that there was frequent contact between patients and pharmacotherapists in the pill placebo conditions, and this may have made an important contribution to the improvement of patients.…”

Section: Discussionmentioning

confidence: 99%

Comparison of psychotherapies for adult depression to pill placebo control groups: a meta-analysis

et al. 2013

View full text Add to dashboard Cite

Background. The effects of antidepressants for treating depressive disorders have been overestimated because of selective publication of positive trials. Reanalyses that include unpublished trials have yielded reduced effect sizes. This in turn has led to claims that antidepressants have clinically insignificant advantages over placebo and that psychotherapy is therefore a better alternative. To test this, we conducted a meta-analysis of studies comparing psychotherapy with pill placebo.Method. Ten 10 studies comparing psychotherapies with pill placebo were identified. In total, 1240 patients were included in these studies. For each study, Hedges' g was calculated. Characteristics of the studies were extracted for subgroup and meta-regression analyses.Results. The effect of psychotherapy compared to pill placebo at post-test was g = 0.25 [95% confidence interval (CI) 0.14-0.36, I 2 = 0%, 95% CI 0-58]. This effect size corresponds to a number needed to treat (NNT) of 7.14 (95% CI 5.00-12.82). The psychotherapy conditions scored 2.66 points lower on the Hamilton Depression Rating Scale (HAMD) than the placebo conditions, and 3.20 points lower on the Beck Depression Inventory (BDI). Some indications for publication bias were found (two missing studies). We found no significant differences between subgroups of the studies and in meta-regression analyses we found no significant association between baseline severity and effect size. Conclusions.Although there are differences between the role of placebo in psychotherapy and pharmacotherapy research, psychotherapy has an effect size that is comparable to that of antidepressant medications. Whether these effects should be deemed clinically relevant remains open to debate.

show abstract

“…Furthermore, few studies include or adjust for placebo response, which has been shown to account for 67.6% of the efficacy observed in antidepressant treatment (Rief et al 2009). Placebo response is a major concern for drug trials, as well as for biomarker investigations, and likely has a significant genetic component (Walsh et al 2002;Tiwari et al 2013;Holmes et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Fabbri

Hosák

Mößner

et al. 2016

The World Journal of Biological Psychiatry

View full text Add to dashboard Cite

Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under-or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in anti-depressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-a receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

show abstract

Meta-analysis of the placebo response in antidepressant trials

Cited by 267 publications

References 32 publications

Lessons learned from placebo groups in antidepressant trials

Lessons learned from placebo groups in antidepressant trials

Comparison of psychotherapies for adult depression to pill placebo control groups: a meta-analysis

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Contact Info

Product

Resources

About