scholarly journals Comparative efficacy of placebos in short-term antidepressant trials for major depression: a secondary meta-analysis of placebo-controlled trials

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lisa Holper ◽  
Michael P. Hengartner
Keyword(s):  
Side Effects ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Antidepressant Drugs ◽  
Depression Scale ◽  
Drug Efficacy ◽  
Controlled Trials ◽  
Hamilton Depression Scale ◽  
Double Blind ◽  
Insignificant Correlation

Abstract Background The issue of unblinded outcome-assessors and patients has repeatedly been stressed as a flaw in allegedly double-blind antidepressant trials. Unblinding bias can for example result from a drug‘s marked side effects. If such unblinding bias is present for a given drug, then it might be expected that the placebos of that drug are rated significantly less effective than that of other antidepressants. Methods To test this hypothesis, the present exploratory analysis conducted a Bayesian network meta-analysis (NMA) comparing the efficacy of 19 different placebos in placebo-controlled trials provided in the dataset by Cipriani et al. (Lancet 2018; 391: 1357–66). Primary outcome was efficacy (continuous) estimated on the standardized mean difference (SMD) scale and defined as the pre-post change on the Hamilton Depression scale (HAMD-17), on which information was available in N = 258 trials. Results Comparative placebo ranking suggested mirtazapine-placebo (SMD -2.0 [− 5.0–1.0 95% CrI]) to be the most, and amitriptyline- (SMD 1.2 [− 1.6–3.9 95% CrI]) and trazodone- (SMD 2.1 [− 0.9–5.2 95% CrI]) placebos to be the least effective placebos. Other placebos suggested to be more effective than amitriptyline- and trazodone-placebos (based on 95% CrIs excluding zero) were citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine placebos. These NMA results were corroborated by the observation that the relative efficacy between drug and placebo was considerably larger for amitriptyline and trazodone than for instance mirtazapine, duloxetine, and venlafaxine, supported by a small and insignificant correlation between drug-efficacy and placebo-efficacy (r = − 0.202, p = 0.408). Discussion The present exploratory NMA indicates that distinguishable side effects of older drugs may unblind outcome-assessors thus resulting in overestimation of the average drug-placebo difference and underrating bias in placebo-arms, particularly for the older antidepressant drugs amitriptyline and trazodone. If confirmed in prospective studies, these findings suggest that efficacy rankings for antidepressants are susceptible to bias and should be considered unreliable or misleading. The analysis is limited by the focus on the single-comparison placebos (76%, i.e., placebos assessed in two-arm trials), since double-comparison placebos (25%, i.e., placebos assessed in three-arm trials) are hard to interpret and therefore not included in the present interpretation. Another limitation is the problem of multiplicity, which was only approximately accounted for in the Bayesian NMA by modelling treatment effects as exchangeable.

scholarly journals Systematic Review with Meta-Analysis: Effectiveness and Safety of Acupuncture as Adjuvant Therapy for Side Effects Management in Drug Therapy-Receiving Breast Cancer Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yau-Tuen Chan ◽  
Ning Wang ◽  
Chi-Wing Tam ◽  
Hor-Yue Tan ◽  
Yuanjun Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Side Effects ◽  
Randomised Controlled Trials ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Real Acupuncture ◽  
Randomised Controlled

Objective. To investigate the potential benefits and safety of acupuncture on managing side effects induced by drug therapies in patients with breast cancer using a PRISMA standard systematic review and meta-analysis. Methods. Published randomised controlled trials from nine databases in English and Chinese language were searched. Trials with a real acupuncture treatment group and a control group with sham acupuncture, no treatment, or waitlist control were included. The primary outcome of this study was the therapeutic effects on five symptoms induced by drug therapies, including gastrointestinal disorder, neuropathy, arthralgia, joint symptoms, and cognitive impairment. The quality of life was assessed as a secondary outcome. The risk of bias of each study was analysed according to the Cochrane Handbook. Results. Sixteen randomised controlled trials with 1189 participants were included in the meta-analysis. The primary outcome and all subgroup analyses showed statistically significant improvements in the management of side effects by real acupuncture. The quality of life of patients has enhanced during the treatment. Conclusion. Although the number of publications is limited, a clear preliminary conclusion could be drawn by the meta-analysis, suggesting the beneficial adjuvant role of acupuncture in patients with breast cancer who receive drug therapies. No serious adverse events were observed from all the RCTs, and the safety of acupuncture is ascertained. More standardised and sophisticated large-scale randomised controlled trials are needed to evaluate the findings further.

Effectiveness and Tolerance of the Hypericum Extract LI 160 in Comparison with Imipramine: Randomized Double-Blind Study with 135 Outpatients

1994 ◽  
Vol 7 (1_suppl) ◽  
pp. 19-23 ◽  
Author(s):  
E.-U. Vorbach ◽  
W.-D. Hübner ◽  
K.-H. Arnoldt
Keyword(s):  
Side Effects ◽  
Depression Scale ◽  
Adjustment Disorder ◽  
Double Blind Study ◽  
Hamilton Depression Scale ◽  
Double Blind ◽  
Single Episode ◽  
Treatment Groups ◽  
Safety Parameters ◽  
Hypericum Extract

In a double-blind comparative study, 135 depressed patients were treated in 20 centers. Inclusion diagnoses were typical depressions with single episode (296.2), several episodes (296.3), depressive neurosis (300.4), and adjustment disorder with depressed mood (309.0) in accordance with DSM-III-R. The dosage was 3 x 300 mg hypericum extract LI 160 or 3 x 25 mg imipramine daily. The treatment lasted for 6 weeks. Main assessment criteria were the Hamilton Depression Scale (HAMD), the Depression Scale according to von Zerssen (D-S) and the Clinical Global Impressions (CGI). In both treatment groups, a parallel reduction of the Hamilton score from 20.2 to 8.8 (LI 160, n = 67) or from 19.4 to 10.7 (imipramine, n = 68), and the transformed D-S point values from 39.6 to 27.2 (LI 160) and 39.0 to 29.2 (imipramine) were found. The analysis of CGI revealed comparable results in both treatment groups. Clinically relevant changes of the safety parameters were not found. In the LI 160 group fewer and milder side effects were found as compared to imipramine.

What do Clinical Trials Tell us About Antidepressant Delayed Onset of Action?

2017 ◽  
Vol 41 (S1) ◽  
pp. S3-S4
Author(s):  
J. Rabinowitz
Keyword(s):  
Rating Scale ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Depression Scale ◽  
Self Report ◽  
Symptom Improvement ◽  
Controlled Trials ◽  
Hamilton Depression Scale ◽  
Onset Of Action ◽  
Individual Patient Level

Response to antidepressants in major depressive disorder is highly variable and determinants are not well understood. Presentation will provide clinical trial data on time to response and determinants of response to antidepressant treatment. Data is from the Innovative Medicines Initiative funded NEWMEDS collaboration, a large public-private collaboration which assembled the largest dataset of individual patient level information from randomized placebo-controlled trials of antidepressant drugs. Studies were conducted by four large pharmaceutical companies. Dataset includes placebo-controlled trials of citalopram, duloxetine, escitalopram, quetiapine and sertraline in adults with MDD. We examined patient and trial-design-related determinants of outcome as measured by change on Hamilton Depression Scale or Montgomery–Asberg Depression Rating Scale in 34 placebo-controlled trials (drug, n = 8260; placebo, n = 3957). While it is conventional for trials to be 6–8 weeks long, data presented will show that drug-placebo differences were observable at week 4 with nearly the same sensitivity and lower dropout rates. Having any of these attributes was significantly associated with greater drug vs. placebo differences on symptom improvement: female, patients being middle aged, increasing proportion of patients on placebo, excluding all patients from centers with high placebo response regardless of active treatment response, using active run in periods and including self-report measures. Proof of concept trials can be shorter and efficiency improved by selecting enriched populations based on clinical and demographic variables, ensuring adequate balance of placebo patients, and carefully selecting and monitoring centers. In addition to improving drug discovery, patient exposure to placebo and experimental treatments can be reduced.Disclosure of interestI have received research grant(s) support and/or travel support and/or speaker fees and/or consultant fees from Takeda, Minerva, Intra-cellular Therapies, Janssen (J&J), Eli Lilly, Pfizer, BiolineRx, Roche, Abraham Pharmaceuticals, Pierre Fabre, Minerva and Amgen.

scholarly journals The Potential Influence of Absence of Blinding Method: Secondary Analysis From Randomized Controlled Trials Concerned Acupuncture for Depression

2020 ◽  
Author(s):  
Rui-Ting Wang ◽  
Ling-Jun Cui ◽  
Jian-Ping Liu ◽  
Mei Han ◽  
Yu-Tong Fei ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Depression Scale ◽  
Experimental Treatment ◽  
Controlled Trials ◽  
Hamilton Depression Scale ◽  
China National Knowledge Infrastructure ◽  
Detection Bias ◽  
Randomized Controlled ◽  
And Control

Abstract Background To evaluate the possibility and impact of performance and detection bias in randomized controlled trials due to lack of the blinding method. MethodsTrials assessing acupuncture for depression published by March 2020 were searched from China National Knowledge Infrastructure database. Through matching, we reassembled the trials of comparing experimental acupuncture and control acupuncture. Meta-analysis with post-treatment HAMD (Hamilton Depression Scale) of the newly reassembled trials was conducted. Changes of HAMD of all included groups were also analyzed, the between groups difference was then analyzed by t-test. All statistical analyses were performed using RevMan 5.3 software. ResultsThirteen pairs of studies were matched from 63 included trials. Re-analysis from the paired studies showed obvious difference of HAMD scales between the experimental and control acupuncture (Mean Difference was -2.95 for HAMD-17, -5.55 for HAMD-24). Re-analysis from all the included groups also showed the statistical difference between groups at four weeks of HAMD-17 (P=0.01), and four/six weeks of HAMD-24 (P<0.01).Conclusion Effectiveness of acupuncture for decreasing the severity of depression was superior in trials that considered acupuncture as experimental treatment, showing performance and detection bias caused by the absence of blinding method is of great significance in acupuncture trials.

The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

1995 ◽  
Vol 74 (04) ◽  
pp. 1064-1070 ◽  
Author(s):  
Marco Cattaneo ◽  
Alan S Harris ◽  
Ulf Strömberg ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Meta Analysis ◽  
Postoperative Blood Loss ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Transfusion Requirements ◽  
The Mean ◽  
Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

scholarly journals Conservative oxygen therapy for critically ill patients: a meta-analysis of randomized controlled trials

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Xiao-Li Chen ◽  
Bei-Lei Zhang ◽  
Chang Meng ◽  
Hui-Bin Huang ◽  
Bin Du
Keyword(s):  
Sensitivity Analysis ◽  
Randomized Controlled Trials ◽  
Critically Ill Patients ◽  
Oxygen Therapy ◽  
Primary Outcome ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Icu Patients ◽  
Randomized Controlled

Abstract Objective Conservative oxygen strategy is recommended in acute illness while its benefit in ICU patients remains controversial. Therefore, we sought to conduct a systematic review and meta-analysis to examine such oxygen strategies’ effect and safety in ICU patients. Methods We searched PubMed, Embase, and the Cochrane database from inception to Feb 15, 2021. Randomized controlled trials (RCTs) that compared a conservative oxygen strategy to a conventional strategy in critically ill patients were included. Results were expressed as mean difference (MD) and risk ratio (RR) with a 95% confidence interval (CI). The primary outcome was the longest follow-up mortality. Heterogeneity, sensitivity analysis, and publication bias were also investigated to test the robustness of the primary outcome. Results We included seven trials with a total of 5265 patients. In general, the conventional group had significantly higher SpO2 or PaO2 than that in the conservative group. No statistically significant differences were found in the longest follow-up mortality (RR, 1.03; 95% CI, 0.97–1.10; I2=18%; P=0.34) between the two oxygen strategies when pooling studies enrolling subjects with various degrees of hypoxemia. Further sensitivity analysis showed that ICU patients with mild-to-moderate hypoxemia (PaO2/FiO2 >100 mmHg) had significantly lower mortality (RR, 1.24; 95% CI, 1.05–1.46; I2=0%; P=0.01) when receiving conservative oxygen therapy. These findings were also confirmed in other study periods. Additional, secondary outcomes of the duration of mechanical ventilation, the length of stay in the ICU and hospital, change in sequential organ failure assessment score, and adverse events were comparable between the two strategies. Conclusions Our findings indicate that conservative oxygen therapy strategy did not improve the prognosis of the overall ICU patients. The subgroup of ICU patients with mild to moderate hypoxemia might obtain prognosis benefit from such a strategy without affecting other critical clinical results.

scholarly journals Impact of maternal supplementation with probiotics during pregnancy on atopic eczema in childhood – a meta-analysis

2011 ◽  
Vol 107 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Katja Doege ◽  
Donata Grajecki ◽  
Birgit-Christiane Zyriax ◽  
Elena Detinkina ◽  
Christine zu Eulenburg ◽  
...  
Keyword(s):  
Atopic Eczema ◽  
Data Extraction ◽  
Meta Analysis ◽  
Significant Risk ◽  
Controlled Trials ◽  
Bacterial Strains ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Study Selection ◽  
The Impact

In the present study, we sought to conduct a literature review of randomised, double-blind, placebo-controlled trials, which assessed the impact of probiotics intake during pregnancy on the development of eczema in children. A meta-analysis was conducted for comparison of the development of atopic eczema in children whose mothers took probiotics during pregnancyv.placebo. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The studies were rated according to their size in order to calculate the influence of individual studies on the meta-analysis. A total of seven randomised, double-blind, placebo-controlled trials, published between 2001 and 2009, were selected from the PubMed and Ovid databases for the meta-analysis. The meta-analysis was performed with statistical software Stata/SE11.0. The completed meta-analysis of the seven studies shows a significant risk reduction for atopic eczema in children aged 2–7 years by the administration of probiotics during pregnancy (reduction 5·7 %;P = 0·022). However, this effect was only significant for lactobacilli (reduction 10·6 %;P = 0·045), but not for a mixture of various bacterial strains as probiotics (difference 3·06 %,P = 0·204). In conclusion, the meta-analysis shows that the administration of lactobacilli during pregnancy prevents atopic eczema in children aged from 2 to 7 years. However, a mixture of various bacterial strains does not affect the development of atopic eczema, independent of whether they contain lactobacilli or not.

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