Is the placebo effect dependent on time? A meta-analysis.

2004 ◽  
pp. 321-332 ◽  
Author(s):  
Harald Walach ◽  
Catarina Maidhof
Keyword(s):  
BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S261-S262
Author(s):  
Brett D M Jones ◽  
Cory R. Weissman ◽  
Jewel Karbi ◽  
Tya Vine ◽  
Louise S. Mulsant ◽  
...  

AimsThe placebo response in depression clinical trials is a major contributing factor for failure to establish the efficacy of novel and repurposed treatments. However, it is not clear as to what the placebo response in treatment-resistant depression (TRD) patients is or whether it differs across treatment modalities. Our objective was to conduct a systematic review and meta-analysis of the magnitude of the placebo response in TRD patients across different treatment modalities and its possible moderators.MethodSearches were conducted on MEDLINE and PsychInfo from inception to January 24, 2020. Only studies that recruited TRD patients and randomization to a placebo (or sham) arm in a pharmacotherapy, brain stimulation, or psychotherapy study were included (PROSPERO 2020 CRD42020190465). The primary outcome was the Hedges’ g for the reported depression scale using a random-effects model. Secondary outcomes included moderators assessed via meta-regression and response and remission rate. Heterogeneity was evaluated using the Egger's Test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks.Result46 studies met our inclusion criteria involving a total of 3083 participants (mean (SD) age: 45.7 (6.2); female: 52.4%). The pooled placebo effect for all modalities was large (N = 3083, g = 1.08 ,95% CI [0.95-1.20)I 2 = 0.1). The placebo effect in studies of specific treatment modalities did not significantly differ: oral medications g = 1.14 (95%CI:0.99-1.29); parenteral medications g = 1.32 (95%CI:0.59-2.04); ayahuasca g = 0.47 (95%CI:-0.28-1.17); rTMS g = 0.93 (95%CI:0.63-1.23); tDCS g = 1.32 (95%CI:0.52-2.11); invasive brain stimulation g = 1.06 (95%CI:0.64-1.47). There were no psychotherapy trials that met our eligibility criteria. Similarly, response and remission rates were comparable across modalities. Heterogeneity was large. Two variables predicted a lager placebo effect: open-label prospective design (B:0.32, 95%CI: 0.05-0.58; p:0.02) and sponsoring by a pharmaceutical or medical device company (B:0.39, 95%CI:0.13-0.65, p:0.004)). No risk of publication bias was found.ConclusionThe overall placebo effect in TRD studies was large (g = 1.08) and did not differ among treatment modalities. A better understanding of the placebo response in TRD will require: standardizing the definition of TRD, head-to-head comparisons of treatment modalities, an assessment of patient expectations and experiences, and standardized reporting of outcomes.


Author(s):  
Biya Tang ◽  
Kirsten Barnes ◽  
Andrew Geers ◽  
Evan Livesey ◽  
Ben Colagiuri

Abstract Background Choice has been proposed as a method of enhancing placebo effects. However, there have been no attempts to systematically evaluate the magnitude, reliability, and moderators of the influence of choice on the placebo effect. Purpose To estimate the effect size of choice on the placebo effect and identify any moderators of this effect. Methods Web of Science, PsycINFO, EMBASE, and PubMed were systematically searched from inception to May 2021 for studies comparing placebo treatment with any form of choice over its administration (e.g., type, timing) to placebo treatment without choice, on any health-related outcome. Random-effects meta-analysis was then used to estimate the effect size associated with the influence of choice on the placebo effect. Meta-regression was subsequently employed to determine the moderating effect of factors such as type of choice, frequency of choice, and size of the placebo effect without choice. Results Fifteen independent studies (N = 1,506) assessing a range of conditions, including pain, discomfort, sleep difficulty, and anxiety, met inclusion criteria. Meta-analysis revealed that choice did significantly enhance the placebo effect (Hedges’ g = 0.298). Size of the placebo effect without choice was the only reliable moderator of this effect, whereby a greater effect of choice was associated with smaller placebo effects without choice. Conclusions Treatment choice can effectively facilitate the placebo effect, but this effect appears more pronounced in contexts where the placebo effect without choice is weaker. Because most evidence to date is experimental, translational studies are needed to test whether providing choice in clinical scenarios where placebo effects are weaker may help boost the placebo effect and thereby improve patient outcomes.


2022 ◽  
pp. 000486742110687
Author(s):  
Masoud Ahmadzad-Asl ◽  
Farnoush Davoudi ◽  
Safoura Mohamadi ◽  
Fatemeh Hadi ◽  
Seyed Aria Nejadghaderi ◽  
...  

Objective: This review aimed to measure the degree of placebo response in panic disorder. Data Sources: We searched major databases up to 31 January 2021, for randomized pharmacotherapy trials published in English. Study Selection: A total of 43 studies met inclusion criteria to be in the analysis (with 174 separate outcome measurements). Data Extraction: Changes in outcome measures from baseline in the placebo group were used to estimate modified Cohen’s d effect size. Results: A total of 43 trials (2392 subjects, 174 outcomes using 27 rating scales) were included in the meta-analysis. Overall placebo effect size was 0.57 (95% confidence interval = [0.50, 0.64]), heterogeneity ( I2: 96.3%). Higher placebo effect size was observed among clinician-rated scales compared to patient reports (0.75 vs 0.35) and among general symptom and anxiety scales compared to panic symptoms and depression scales (0.92 and 0.64 vs 0.56 and 0.54, respectively). There was an upward trend in effect size over the publication period ( r = 0.02, p = 0.002) that was only significant among clinician-rated scales ( r = 0.02, p = 0.011). There was no significant publication bias, Egger’s test ( p = 0.08). Conclusion: We observed a substantial placebo effect size in panic disorder. This effect was more prominent for some aspects of panic disorder psychopathology than for others and was correlated with the source of the assessment and publication year. This finding has implications both for research design, to address the heterogeneity and diversity in placebo responses, and for clinical practice to ensure optimal quality of care. Systematic review registration number: PROSPERO, CRD42019125979.


Cartilage ◽  
2020 ◽  
pp. 194760352090659 ◽  
Author(s):  
Davide Previtali ◽  
Giulia Merli ◽  
Giorgio Di Laura Frattura ◽  
Christian Candrian ◽  
Stefano Zaffagnini ◽  
...  

Objectives To quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated. Design Meta-analysis of randomized controlled trials; Level of evidence, 2. PubMed, Web of Science, Cochrane Library, and grey literature databases were searched on January 8, 2020, using the string: (knee) AND (osteoarthritis OR OA) AND (injections OR intra-articular) AND (saline OR placebo). The following inclusion criteria were used: double-blind, randomized controlled trials on knee osteoarthritis, including a placebo arm on saline injections. The primary outcome was pain variation. Risk of bias was assessed using the RoB 2.0 tool, and quality of evidence was graded following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) guidelines. Results Out of 2,363 records, 50 articles on 4,076 patients were included. The meta-analysis showed significant improvements up to the 6-month follow-up: Visual Analogue Scale (VAS)-pain −13.4 mean difference (MD) (95% confidence interval [CI]: −21.7/−5.1; P < 0.001), Western Ontario and McMaster Osteoarthritis Index (WOMAC)-pain −3.3 MD (95% CI: −3.9/−2.7; P < 0.001). Other significant improvements were WOMAC-stiffness −1.1 MD (95% CI: −1.6/−0.6; P < 0.001), WOMAC-function −10.1 MD (95% CI: −12.2/−8.0; P < 0.001), and Evaluator Global Assessment −21.4 MD (95% CI: −29.2/−13.6; P < 0.001). The responder rate was 52% (95% CI: 40% to 63%). Improvements were greater than the “minimal clinically important difference” for all outcomes (except 6-month VAS-pain). The level of evidence was moderate for almost all outcomes. Conclusions The placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.


2016 ◽  
Vol 68 (6) ◽  
pp. 1540-1550 ◽  
Author(s):  
Erkan Demirkaya ◽  
Stefano Lanni ◽  
Francesca Bovis ◽  
Roberta Galasso ◽  
Angelo Ravelli ◽  
...  

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Henning Zeidler

This paper addresses the role of paracetamol in placebo-controlled osteoarthritis (OA) trials and the potential contribution to the large placebo response in such trials. Paracetamol is used as rescue medication in nearly all OA placebo-controlled trials. Triggered by the discussion about the placebo effect in general and because of the lack of systematic reviews of placebo effect in OA trials, a recent meta-analysis examined the placebo effect and its potential determinants in the treatment of OA, as the main result came out that placebo is very effective in the treatment of OA, especially for pain, stiffness, and self-reported function. However, mostly limited data are available from published OA trials on the starting dose, final dose, dose over time of paracetamol use, and the percentage of patients who used rescue medication during the study. Paracetamol may be an important additional simulated effect of placebo administration mimicking the true placebo effect and thus a missing link contributing partially to the large placebo response in OA trials. Therefore, the positive effect of paracetamol on symptom relief as well as the need for standardized recording of rescue medication should be taken into account when designing, executing, and interpreting placebo-controlled OA studies.


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