Dataset Information

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

ABSTRACT: 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.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.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.

SUBMITTER: Brunoni AR

PROVIDER: S-EPMC2653635 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Brunoni André Russowsky AR Lopes Mariana M Kaptchuk Ted J TJ Fregni Felipe F

PloS one 20090318 3

<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-an ...[more]

PMID: 19293925

Similar Datasets

Project description:BackgroundPlacebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms.MethodsWe searched ClinicalTrials.gov , CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a random-effects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317 .ResultsEighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8-12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = - 0.32, 95% CI [- 0.39, - 0.25], in repetitive behaviors - 0.23[- 0.32, - 0.15] and in scales measuring overall core symptoms - 0.36 [- 0.46, - 0.26]. Overall, 19%, 95% CI [16-22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain.LimitationsAbout 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers.ConclusionsPlacebo response in ASD was substantial and predicted by design- and participant-related factors, which could inform the design of future trials in order to improve the detection of efficacy in core symptoms. Potential solutions could be the minimization and careful selection of study sites as well as rigorous participant enrollment and the use of measurements of change not solely dependent on caregivers.

Project description:OBJECTIVES:To systematically review and compare the efficacy of all available home-based non-pharmacological treatments of depression. DESIGN:Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES:Medline, Scopus and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched since inceptions to 7 August 2016. ELIGIBILITY CRITERIA:Randomised controlled trials comparing the efficacy of home-based non-pharmacological interventions with usual care of patients with depression were included in the review. MAIN OUTCOMES:Depression symptom scores and disease remission rates at the end of treatment. RESULTS:Seventeen studies were included in the review. Home-based non-pharmacological interventions were categorised as (1) home-based psychological intervention, (2) home-based exercise intervention, (3) combined home-based psychological intervention with exercise intervention and (4) complementary medicine. Complementary medicine approaches were excluded from the meta-analysis due to heterogeneity. The standardised mean differences of post-treatment depression symptom scores between usual care groups and home-based psychological intervention, home-based exercise intervention and combined home-based psychological intervention with exercise intervention were âˆ'0.57 (95% CI âˆ'0.84 to âˆ'0.31), âˆ'1.03 (95% CI âˆ'2.89 to 0.82) and âˆ'0.78 (95% CI âˆ'1.09 to âˆ'0.47), respectively. These results suggest that only home-based psychological intervention and combined home-based psychological intervention with exercise intervention could significantly decrease depression scores. Compared with usual care groups, the disease remission rate was also significantly higher for home-based psychological intervention (pooled risk ratio=1.53; 95%â€‰CI 1.19 to 1.98) and combined home-based psychological intervention with exercise intervention (pooled risk ratio=3.47; 95%â€‰CI 2.11 to 5.70). Of all the studied interventions, combined home-based psychological intervention with exercise intervention had the highest probability of resulting in disease remission. CONCLUSION:Our study confirms the efficacy of home-based psychological intervention and combined home-based psychological intervention with exercise intervention in the treatment of depression. Combined home-based psychological intervention and exercise intervention was the best treatment and should be considered for inclusion in clinical guidelines for managing depression.

Project description:ObjectivesTo assess the benefits and harms of reboxetine versus placebo or selective serotonin reuptake inhibitors (SSRIs) in the acute treatment of depression, and to measure the impact of potential publication bias in trials of reboxetine.DesignSystematic review and meta-analysis including unpublished data.Data sourcesBibliographic databases (Medline, Embase, PsycINFO, BIOSIS, and Cochrane Library), clinical trial registries, trial results databases, and regulatory authority websites up until February 2009, as well as unpublished data from the manufacturer of reboxetine (Pfizer, Berlin).Eligibility criteriaDouble blind, randomised, controlled trials of acute treatment (six weeks or more) with reboxetine versus placebo or SSRIs in adults with major depression.Outcome measuresRemission and response rates (benefit outcomes), as well as rates of patients with at least one adverse event and withdrawals owing to adverse events (harm outcomes).Data extraction and data synthesisThe procedures for data extraction and assessment of risk of bias were always conducted by one person and checked by another. If feasible, data were pooled by meta-analyses (random effects model). Publication bias was measured by comparing results of published and unpublished trials.ResultsWe analysed 13 acute treatment trials that were placebo controlled, SSRI controlled, or both, which included 4098 patients. Data on 74% (3033/4098) of these patients were unpublished. In the reboxetine versus placebo comparison, no significant differences in remission rates were shown (odds ratio 1.17, 95% confidence interval 0.91 to 1.51; P=0.216). Substantial heterogeneity (I(2)=67.3%) was shown in the meta-analysis of the eight trials that investigated response rates for reboxetine versus placebo. A sensitivity analysis that excluded a small inpatient trial showed no significant difference in response rates between patients receiving reboxetine and those receiving placebo (OR 1.24, 95% CI 0.98 to 1.56; P=0.071; I(2)=42.1%). Reboxetine was inferior to SSRIs (fluoxetine, paroxetine, and citalopram) for remission rates (OR 0.80, 95% CI 0.67 to 0.96; P=0.015) and response rates (OR 0.80, 95% CI 0.67 to 0.95; P=0.01). Reboxetine was inferior to placebo for both harm outcomes (P<0.001 for both), and to fluoxetine for withdrawals owing to adverse events (OR 1.79, 95% CI 1.06 to 3.05; P=0.031). Published data overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up to 23%, and also underestimated harm.ConclusionsReboxetine is, overall, an ineffective and potentially harmful antidepressant. Published evidence is affected by publication bias, underlining the urgent need for mandatory publication of trial data.

Project description:ObjectivesThis study aims to summarise the evidence on more than 140 pharmacological and non-pharmacological treatment options for major depressive disorder (MDD) and to evaluate the confidence that patients and clinicians can have in the underlying science about their effects.DesignThis is a review of systematic reviews.Data sourcesThis study used MEDLINE, Embase, Cochrane Library, PsycINFO and Epistemonikos from 2011 up to February 2017 for systematic reviews of randomised controlled trials in adult patients with acute-phase MDD.MethodsWe dually reviewed abstracts and full-text articles, rated the risk of bias of eligible systematic reviews and graded the strength of evidence.ResultsNineteen systematic reviews provided data on 28 comparisons of interest. For general efficacy, only second-generation antidepressants were supported with high strength evidence, presenting small beneficial treatment effects (standardised mean difference: -0.35; 95% CI -0.31 to -0.38), and a statistically significantly higher rate of discontinuation because of adverse events than patients on placebo (relative risk (RR) 1.88; 95%?CI 1.0 to 3.28).Only cognitive behavioural therapy is supported by reliable evidence (moderate strength of evidence) to produce responses to treatment similar to those of second-generation antidepressants (45.5% vs 44.2%; RR 1.10; 95%?CI 0.93 to 1.30). All remaining comparisons of non-pharmacological treatments with second-generation antidepressants either led to inconclusive results or had substantial methodological shortcomings (low or insufficient strength of evidence).ConclusionsIn contrast to pharmacological treatments, the majority of non-pharmacological interventions for treating patients with MDD are not evidence based. For patients with strong preferences against pharmacological treatments, clinicians should focus on therapies that have been compared directly with antidepressants.Trial registration numberInternational Prospective Register of Systematic Reviews (PROSPERO) registration number: 42016035580.

Project description:Objective To assess the effectiveness of citalopram for major depressive disorder (MDD) in adults, in a systematic review of all published, randomised, double-blind studies comparing it with a placebo. Data sources Cochrane Central Register of Controlled Trials, Medline, PsychINFO and Embase. Study selection Randomised, double-blind, placebo-controlled studies of citalopram in adults with MDD were included. Studies with medically ill or treatment resistant subjects were excluded, as were studies of relapse prevention. Remission of MDD was defined as a primary outcome, and response or change from baseline scores were defined as secondary. Data extraction Remission, response and symptom improvement scores on the Hamilton Depression Scale, Montgomery-Asberg Depression Rating Scale and Clinical Global Impressions-Severity scales were extracted. A random-effects meta-analysis was carried out on the response rates and symptom improvement scores. Included studies were examined for the presence of bias and small study effects. Results Eight studies (n=2025) met the inclusion criteria. Two studies provided data on remission, but only one of these showed a significant difference between citalopram and placebo (RR=1.59, 95% CI 1.10 to 2.31). Meta-analysis of response rates in five studies (n=1010) revealed significant superiority of citalopram (RR=1.42, 95% CI 1.17 to 1.73). Meta-analysis of change from baseline scores in five studies (n=1541) gave a standardised mean difference (Hedges' g) of -0.27 (95% CI -0.38 to to -0.16), showing a reduction in MDD symptoms to be significant for citalopram relative to placebo. There was no evidence of any significant small study effects. The overall quality of reporting was poor, with insufficient information on the methodology or outcomes. Seven studies received industry sponsorship. Conclusions Data concerning remission rates for citalopram, relative to placebo, are inconclusive. Response rates and symptom reduction scores in citalopram-treated patients with MDD are significantly better relative to placebo treatment, according to a meta-analysis of published reports. Evaluation of unpublished data is necessary to assess more definitively the effectiveness of citalopram for MDD.

Project description:BackgroundA rigorous systematic review and meta-analysis focused on randomised controlled trials (RCTs) of non-individualised homeopathic treatment has not previously been reported. We tested the null hypothesis that the main outcome of treatment using a non-individualised (standardised) homeopathic medicine is indistinguishable from that of placebo. An additional aim was to quantify any condition-specific effects of non-individualised homeopathic treatment.MethodsLiterature search strategy, data extraction and statistical analysis all followed the methods described in a pre-published protocol. A trial comprised 'reliable evidence' if its risk of bias was low or it was unclear in one specified domain of assessment. 'Effect size' was reported as standardised mean difference (SMD), with arithmetic transformation for dichotomous data carried out as required; a negative SMD indicated an effect favouring homeopathy.ResultsForty-eight different clinical conditions were represented in 75 eligible RCTs. Forty-nine trials were classed as 'high risk of bias' and 23 as 'uncertain risk of bias'; the remaining three, clinically heterogeneous, trials displayed sufficiently low risk of bias to be designated reliable evidence. Fifty-four trials had extractable data: pooled SMD was -0.33 (95% confidence interval (CI) -0.44, -0.21), which was attenuated to -0.16 (95% CI -0.31, -0.02) after adjustment for publication bias. The three trials with reliable evidence yielded a non-significant pooled SMD: -0.18 (95% CI -0.46, 0.09). There was no single clinical condition for which meta-analysis included reliable evidence.ConclusionsThe quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment.

Project description:Background:There is debate in the literature as to whether inclusion of a placebo arm may alter characteristics of antidepressant trials. However, previous research has focused on response rates of various antidepressants on average only, ignoring potential differences among drugs or other aspects of trial findings. Little is known about the impact of a placebo arm on all-cause dropout and dropout due to adverse events. Methods:We carried out a systematic review of published and unpublished double-blind randomized controlled trials (RCTs) for the acute treatment of unipolar major depression (update: January 2016). The probability of being allocated to placebo (?) was the exposure of interest, and we examined its influence on responders (efficacy), all-cause dropouts (acceptability) and dropouts due to adverse events (tolerability), while accounting for differences in drugs, trials and patient characteristics in multivariate random effects meta-regression. Results:We included 421 studies (68 305 participants) comparing 16 antidepressants or placebo; ? ranged from 20% to 50%. Response rate was lower [risk ratio (RR) 0.87; 95% confidence interval (CI) 0.83, 0.92] and all-cause dropout rate higher (RR 1.19; 95% CI 1.08, 1.31) for the same antidepressants in placebo-controlled trials compared with head-to-head trials. The probability of responding decreased by 3% (95% CI 2-5%) for every 10% increase in ?, whereas the risk of all-cause dropout increased by 4% (95% CI 1-7%). Tolerability was unaffected by ?. Response rate was inversely correlated with dropouts due to any cause (correlation coefficient -0.48; 95% CI -0.58, -0.36) and due to adverse events (-0.34; 95% CI -0.44, -0.23). Conclusions:For the same antidepressant, response rate was on average smaller and dropouts higher when placebo was included; however, no association was found with dropouts due to adverse events. Decreased patient expectations, larger dropout rates and use of inappropriate statistical methods to impute missing data may explain this phenomenon. The findings call for caution in the integration of randomized evidence involving placebo arms.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets