Effects of treatment classifications in network meta-analysis

Objectives Network meta-analysis is a popular tool to simultaneously compare multiple treatments and improve treatment effect estimates. However, no widely accepted guidelines are available to classify the treatment nodes in a network meta-analysis, and the node-making process was often insufficiently reported. We aim at empirically examining the impact of different treatment classifications on network meta-analysis results. Methods We collected nine published network meta-analyses with various disease outcomes; each contained some similar treatments that may be lumped. The Bayesian random-effects model was applied to these network meta-analyses before and after lumping the similar treatments. We estimated the odds ratios and their 95% credible intervals in the original and lumped network meta-analyses. We used the adjusted deviance information criterion to assess the model performance in the lumped network meta-analyses, and used the ratios of credible interval lengths and ratios of odds ratios to quantitatively evaluate the estimates’ changes due to lumping. In addition, the unrelated mean effect model was applied to examine the extents of evidence inconsistency. Results The estimated odds ratios of many treatment comparisons had noticeable changes due to lumping; many of their precisions were substantially improved. The deviance information criterion values reduced after lumping similar treatments in seven (78%) network meta-analyses, indicating better model performance. Substantial evidence inconsistency was detected in only one network meta-analysis. Conclusions Different ways of classifying treatment nodes may substantially affect network meta-analysis results. Including many insufficiently compared treatments and analysing them as separate nodes may not yield more precise estimates. Researchers should report the node-making process in detail and investigate the results’ robustness to different ways of classifying treatments.

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When does the use of individual patient data in network meta-analysis make a difference? A simulation study

BMC Medical Research Methodology ◽

10.1186/s12874-020-01198-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Steve Kanters ◽

Mohammad Ehsanul Karim ◽

Kristian Thorlund ◽

Aslam Anis ◽

Nick Bansback

Keyword(s):

Simulation Study ◽

Treatment Effect ◽

Mean Squared Error ◽

Individual Patient Data ◽

Meta Analysis ◽

Model Performance ◽

Patient Data ◽

Meta Regression ◽

Treatment Comparisons ◽

The Impact

Abstract Background The use of individual patient data (IPD) in network meta-analyses (NMA) is rapidly growing. This study aimed to determine, through simulations, the impact of select factors on the validity and precision of NMA estimates when combining IPD and aggregate data (AgD) relative to using AgD only. Methods Three analysis strategies were compared via simulations: 1) AgD NMA without adjustments (AgD-NMA); 2) AgD NMA with meta-regression (AgD-NMA-MR); and 3) IPD-AgD NMA with meta-regression (IPD-NMA). We compared 108 parameter permutations: number of network nodes (3, 5 or 10); proportion of treatment comparisons informed by IPD (low, medium or high); equal size trials (2-armed with 200 patients per arm) or larger IPD trials (500 patients per arm); sparse or well-populated networks; and type of effect-modification (none, constant across treatment comparisons, or exchangeable). Data were generated over 200 simulations for each combination of parameters, each using linear regression with Normal distributions. To assess model performance and estimate validity, the mean squared error (MSE) and bias of treatment-effect and covariate estimates were collected. Standard errors (SE) and percentiles were used to compare estimate precision. Results Overall, IPD-NMA performed best in terms of validity and precision. The median MSE was lower in the IPD-NMA in 88 of 108 scenarios (similar results otherwise). On average, the IPD-NMA median MSE was 0.54 times the median using AgD-NMA-MR. Similarly, the SEs of the IPD-NMA treatment-effect estimates were 1/5 the size of AgD-NMA-MR SEs. The magnitude of superior validity and precision of using IPD-NMA varied across scenarios and was associated with the amount of IPD. Using IPD in small or sparse networks consistently led to improved validity and precision; however, in large/dense networks IPD tended to have negligible impact if too few IPD were included. Similar results also apply to the meta-regression coefficient estimates. Conclusions Our simulation study suggests that the use of IPD in NMA will considerably improve the validity and precision of estimates of treatment effect and regression coefficients in the most NMA IPD data-scenarios. However, IPD may not add meaningful validity and precision to NMAs of large and dense treatment networks when negligible IPD are used.

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Peto odds ratios demonstrate no advantage over classic odds ratios in meta-analysis of binary rare outcomes

10.1101/2020.10.13.20212290 ◽

2020 ◽

Author(s):

Chang Xu ◽

Luis Furuya-Kanamori ◽

Lifeng Lin ◽

Suhail A. Doi

Keyword(s):

Event Rate ◽

Meta Analysis ◽

Rare Event ◽

Effect Sizes ◽

Binary Outcomes ◽

Odds Ratios ◽

P Values ◽

Cochrane Database ◽

Meta Analyses ◽

The Impact

AbstractIn this study, we examined the discrepancy between large studies and small studies in meta-analyses of rare event outcomes and the impact of Peto versus the classic odds ratios (ORs) through empirical data from the Cochrane Database of Systematic Reviews that collected from January 2003 to May 2018. Meta-analyses of binary outcomes with rare events (event rate ≤5%), with at least 5 studies, and with at least one large study (N≥1000) were extracted. The Peto and classic ORs were used as the effect sizes in the meta-analyses, and the magnitude and direction of the ORs of the meta-analyses of large studies versus small studies were compared. The p-values of the meta-analyses of small studies were examined to assess if the Peto and the classic OR methods gave similar results. Totally, 214 meta-analyses were included. Over the total 214 pairs of pooled ORs of large studies versus pooled small studies, 66 (30.84%) had a discordant direction (kappa=0.33) when measured by Peto OR and 69 (32.24%) had a discordant direction (kappa=0.22) when measured by classic OR. The Peto ORs resulted in smaller p-values compared to classic ORs in a substantial (83.18%) number of cases. In conclusion, there is considerable discrepancy between large studies and small studies among the results of meta-analyses of sparse data. The use of Peto odds ratios does not improve this situation and is not recommended as it may result in less conservative error estimation.

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Effects of Sport-Based Interventions on Children’s Executive Function: A Systematic Review and Meta-Analysis

Brain Sciences ◽

10.3390/brainsci11060755 ◽

2021 ◽

Vol 11 (6) ◽

pp. 755

Author(s):

Falonn Contreras-Osorio ◽

Christian Campos-Jara ◽

Cristian Martínez-Salazar ◽

Luis Chirosa-Ríos ◽

Darío Martínez-García

Keyword(s):

Systematic Review ◽

Working Memory ◽

Executive Function ◽

Inhibitory Control ◽

Cognitive Flexibility ◽

Meta Analysis ◽

Scientific Evidence ◽

Healthy Children ◽

Meta Analyses ◽

The Impact

One of the most studied aspects of children’s cognitive development is that of the development of the executive function, and research has shown that physical activity has been demonstrated as a key factor in its enhancement. This meta-analysis aims to assess the impact of specific sports interventions on the executive function of children and teenagers. A systematic review was carried out on 1 November 2020 to search for published scientific evidence that analysed different sports programs that possibly affected executive function in students. Longitudinal studies, which assessed the effects of sports interventions on subjects between 6 and 18 years old, were identified through a systematic search of the four principal electronic databases: Web of Science, PubMed, Scopus, and EBSCO. A total of eight studies, with 424 subjects overall, met the inclusion criteria and were classified based on one or more of the following categories: working memory, inhibitory control, and cognitive flexibility. The random-effects model for meta-analyses was performed with RevMan version 5.3 to facilitate the analysis of the studies. Large effect sizes were found in all categories: working memory (ES −1.25; 95% CI −1.70; −0.79; p < 0.0001); inhibitory control (ES −1.30; 95% CI −1.98; −0.63; p < 0.00001); and cognitive flexibility (ES −1.52; 95% CI −2.20; −0.83; p < 0.00001). Our analysis concluded that healthy children and teenagers should be encouraged to practice sports in order to improve their executive function at every stage of their development.

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A protocol for the systematic review and meta-analysis of thigmotactic behaviour in the open field test in rodent models associated with persistent pain

BMJ Open Science ◽

10.1136/bmjos-2020-100135 ◽

2021 ◽

Vol 5 (1) ◽

pp. e100135

Author(s):

Xue Ying Zhang ◽

Jan Vollert ◽

Emily S Sena ◽

Andrew SC Rice ◽

Nadia Soliman

Keyword(s):

Systematic Review ◽

Outcome Measure ◽

Meta Analysis ◽

Persistent Pain ◽

Effect Sizes ◽

Bias Assessment ◽

Animal Pain ◽

Trim And Fill ◽

Meta Analyses ◽

The Impact

ObjectiveThigmotaxis is an innate predator avoidance behaviour of rodents and is enhanced when animals are under stress. It is characterised by the preference of a rodent to seek shelter, rather than expose itself to the aversive open area. The behaviour has been proposed to be a measurable construct that can address the impact of pain on rodent behaviour. This systematic review will assess whether thigmotaxis can be influenced by experimental persistent pain and attenuated by pharmacological interventions in rodents.Search strategyWe will conduct search on three electronic databases to identify studies in which thigmotaxis was used as an outcome measure contextualised to a rodent model associated with persistent pain. All studies published until the date of the search will be considered.Screening and annotationTwo independent reviewers will screen studies based on the order of (1) titles and abstracts, and (2) full texts.Data management and reportingFor meta-analysis, we will extract thigmotactic behavioural data and calculate effect sizes. Effect sizes will be combined using a random-effects model. We will assess heterogeneity and identify sources of heterogeneity. A risk-of-bias assessment will be conducted to evaluate study quality. Publication bias will be assessed using funnel plots, Egger’s regression and trim-and-fill analysis. We will also extract stimulus-evoked limb withdrawal data to assess its correlation with thigmotaxis in the same animals. The evidence obtained will provide a comprehensive understanding of the strengths and limitations of using thigmotactic outcome measure in animal pain research so that future experimental designs can be optimised. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and disseminate the review findings through publication and conference presentation.

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Attenuation of maternal weight gain impacts infant birthweight: systematic review and meta-analysis

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174418000879 ◽

2018 ◽

Vol 10 (4) ◽

pp. 387-405 ◽

Cited By ~ 4

Author(s):

C. J. Bennett ◽

R. E. Walker ◽

M. L. Blumfield ◽

J. Ma ◽

F. Wang ◽

...

Keyword(s):

Weight Gain ◽

Gestational Age ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Adverse Outcomes ◽

Large For Gestational Age ◽

Maternal Weight ◽

Clinical Trial Registry ◽

Meta Analyses ◽

The Impact

AbstractDespite many interventions aiming to reduce excessive gestational weight gain (GWG), it is currently unclear the impact on infant anthropometric outcomes. The aim of this review was to evaluate offspring anthropometric outcomes in studies designed to reduce GWG. A systematic search of seven international databases, one clinical trial registry and three Chinese databases was conducted without date limits. Studies were categorised by intervention type: diet, physical activity (PA), lifestyle (diet + PA), other, gestational diabetes mellitus (GDM) (diet, PA, lifestyle, metformin and other). Meta-analyses were reported as weighted mean difference (WMD) for birthweight and birth length, and risk ratio (RR) for small for gestational age (SGA), large for gestational age (LGA), macrosomia and low birth weight (LBW). Collectively, interventions reduced birthweight, risk of macrosomia and LGA by 71 g (WMD: −70.67, 95% CI −101.90 to −39.43,P<0.001), 16% (RR: 0.84, 95% CI 0.73–0.98,P=0.026) and 19% (RR: 0.81, 95% CI 0.69–0.96,P=0.015), respectively. Diet interventions decreased birthweight and LGA by 99 g (WMD −98.80, 95% CI −178.85 to −18.76,P=0.016) and 65% (RR: 0.35, 95% CI 0.17–0.72,P=0.004). PA interventions reduced the risk of macrosomia by 51% (RR: 0.49, 95% CI 0.26–0.92,P=0.036). In women with GDM, diet and lifestyle interventions reduced birthweight by 211 and 296 g, respectively (WMD: −210.93, 95% CI −374.77 to −46.71,P=0.012 and WMD:−295.93, 95% CI −501.76 to −90.10,P=0.005, respectively). Interventions designed to reduce excessive GWG lead to a small reduction in infant birthweight and risk of macrosomia and LGA, without influencing the risk of adverse outcomes including LBW and SGA.

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The Optimal Time of Applying Enteral Immunonutrition in Esophageal Cancer Patients Receiving Esophagectomy: A Network Meta-Analysis of Randomized Clinical Trials

10.21203/rs.3.rs-235527/v1 ◽

2021 ◽

Author(s):

Xu Tian ◽

Yan-Fei Jin ◽

Zhao-Li Zhang ◽

Hui Chen ◽

Wei-Qing Chen ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Patients ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Infectious Complications ◽

Cochrane Library ◽

Optimal Time ◽

Registration Number ◽

Meta Analyses ◽

The Impact

Abstract Background: Enteral immunonutrition (EIN) has been extensively applied in cancer patients, however its role in esophageal cancer (EC) patients receiving esophagectomy remains unclear. We performed this network meta-analysis to investigate the impact of EIN on patients undergoing surgery for EC and further determine the optimal time of applying EIN.Methods: We searched PubMed, EMBASE, Cochrane library, and China National Knowledgement Infrastructure (CNKI) to identify eligible studies. Categorical data was expressed as the odds ratio with 95% confidence interval (CI), and continuous data was expressed as mean difference (MD) with 95% CI. Pair-wise and network meta-analysis was performed to evaluate the impact of EIN on clinical outcomes using RevMan 5.3 and ADDIS V.1.16.8 softwares. The surface under the cumulative ranking curve (SUCRA) was calculated to rank all nutritional regimes.Results: Total 14 studies involving 1071 patients were included. Pair-wise meta-analysis indicated no difference between EIN regardless of the application time and standard EN (SEN), however subgroup analyses found that postoperative EIN was associated with decreased incidence of total infectious complications (OR=0.47; 95%CI=0.26 to 0.84; p=0.01) and pneumonia (OR=0.47; 95%CI=0.25 to 0.90; p=0.02) and shortened LOH (MD=-1.01; 95%CI=-1.44 to -0.57; p<0.001) compared to SEN, which were all supported by network meta-analyses. Ranking probability analysis further indicated that postoperative EIN has the highest probability of being the optimal option in terms of these three outcomes.Conclusions: Postoperative EIN should be preferentially utilized in EC patients undergoing esophagectomy because it has optimal potential of decreasing the risk of total infectious complications and pneumonia and shortening LOH.OSF registration number: 10.17605/OSF.IO/KJ9UY.

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P261 Systematic review with meta-analysis: The impact of concomitant immune-mediated diseases on the disease course of inflammatory bowel disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.390 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S280-S281

Author(s):

M Attauabi ◽

M Zhao ◽

F Bendtsen ◽

J Burisch

Keyword(s):

Biologic Therapy ◽

Meta Analysis ◽

Multidisciplinary Care ◽

Disease Course ◽

Immune Mediated ◽

Increased Risk ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Meta Analyses ◽

The Impact

Abstract Background Several studies have shown an association between inflammatory bowel diseases [IBD] and immune-mediated diseases [IMIDs], but data on the impact of co-occurring IMIDs on IBD course are inconsistent. The aim of this study was to investigate the impact of co-occurring IMIDs on IBD phenotype and disease course. Methods PubMed and EMBASE were searched from database inception through December 2018 and updated in October 2019 for studies reporting prevalences or odds, risks or hazard ratios of IBD-related disease outcomes in patients with and without co-existing IMIDs. Meta-analyses were performed to estimate summary prevalences and risks of the outcomes which included disease extension, IBD-related surgery and hospitalisation, malignancy, mortality and need of medication (biologic therapy, steroids and immunomodulators). IMIDs were stratified into primary sclerosing cholangitis [PSC] and ‘IMIDs other than PSC’. Results A total of 93 studies comprising 14,307 IBD patients with IMIDs and 3,409,914 IBD patients without IMIDs were included in the study. Summary risks and prevalences with 95% confidence intervals for each outcome are presented in figures 1 and 2, respectively. The following results are all significant (p < 0.05). Compared with patients without co-occurring IMIDs, patients with ulcerative colitis [UC] and co-occurring IMIDs other than PSC more frequently received immunomodulators and steroids, and patients with Crohn’s disease [CD] and concomitant IMIDs other than PSC more often received biologic therapy. UC patients with co-existing IMIDs other than PSC more often underwent IBD-related surgery, while patients with CD and PSC received fewer surgeries. In addition, UC patients with co-occurring PSC were at increased risk for having extensive colitis, pancolitis, and malignancies. Patients with UC and PSC had a higher mortality rate, but no difference was found among patients with IMIDs other than PSC. PSC did not influence hospitalisation rates among IBD patients. Conclusion This meta-analysis found that IBD patients with co-existing IMIDs have a different disease course than patients without concomitant IMIDs. This study emphasises the importance of multidisciplinary care of IBD and that physicians caring for IBD patients need to be aware of IMIDs as a prognostic factor.

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Prevalence of extra-articular manifestations in psoriatic arthritis: a systematic review and meta-analysis

Rheumatology ◽

10.1093/rheumatology/keaa062 ◽

2020 ◽

Vol 59 (9) ◽

pp. 2199-2206 ◽

Cited By ~ 4

Author(s):

Bradley Pittam ◽

Sonal Gupta ◽

Nicholas L Harrison ◽

Selina Robertson ◽

David M Hughes ◽

...

Keyword(s):

Radiographic Progression ◽

Meta Analysis ◽

Response To Treatment ◽

Disease Outcomes ◽

Disease Mechanisms ◽

Prevalence Estimates ◽

Study Characteristics ◽

Meta Analyses ◽

The Impact ◽

Nail Disease

Abstract Objective To describe the prevalence of extra-articular manifestations—enthesitis, dactylitis, nail disease, uveitis and IBD—in PsA, and their impact on longitudinal disease outcomes. Methods We searched Medline, PubMed, Scopus and Web of Science using a predefined protocol in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies using imaging to define extra-articular manifestations (EAMs) were excluded. Where possible, we performed meta-analyses of prevalence estimates, reported as percentages (95% CI). Heterogeneity (I2 statistic) was examined according to study characteristics. Results We identified 65 studies amounting to a total of 163 299 PsA patients. Enthesitis was assessed in 29 studies with an average prevalence of 30% (95% CI: 24%, 38%). Dactylitis was reported in 35 studies with an average prevalence of 25% (95% CI: 20%, 31%). Nail disease was present in 60% (95% CI: 52%, 68%) across 26 studies, but definitions were often unclear. Uveitis (3.2%; 95% CI: 1.9%, 5.3%) and IBD (3.3%; 95% CI: 1.5%, 7.1%) were less common. Heterogeneity was high (>95%) in all meta-analyses, but could not be explained by study characteristics. No studies examined the impact of EAMs on longitudinal disease outcomes, except that dactylitis increases radiographic progression. Conclusion Enthesitis, dactylitis and nail disease are highly prevalent in PsA, but not uveitis and IBD. EAM patterns differ from axial SpA despite their shared disease mechanisms, which may help further understand differences between spondyloarthritides. More studies are needed on the impact of EAMs on disease outcomes such as response to treatment.

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Management of haemorrhoids: protocol of an umbrella review of systematic reviews and meta-analyses

BMJ Open ◽

10.1136/bmjopen-2019-035287 ◽

2020 ◽

Vol 10 (3) ◽

pp. e035287

Author(s):

Min Chen ◽

Tai-Chun Tang ◽

Tao-Hong He ◽

Yong-Jun Du ◽

Di Qin ◽

...

Keyword(s):

Systematic Reviews ◽

Meta Analysis ◽

Random Effect Model ◽

Current Evidence ◽

Cochrane Library ◽

Final Report ◽

Umbrella Review ◽

Effect Model ◽

Meta Analyses ◽

The Impact

IntroductionThe prevalence of haemorrhoidal diseases was high in general population, and many treatments are proposed for the management of haemorrhoids. The treatments include conservative and surgical interventions; the credibility and strength of current evidence of their effectiveness are not comprehensively evaluated. We aim to evaluate the credibility of systematic reviews and meta-analyses that assess the effectiveness of the treatments for haemorrhoidal diseases through an umbrella review.Methods and analysisWe will search Ovid Medline, Embase, Cochrane library and Web of Science from inception to March 2020 without any language restriction. We will include meta-analyses that examine the effectiveness of treatments in the management of haemorrhoids. Two reviewers will independently screen the titles and abstracts of retrieved articles, and they will extract data from the included meta-analyses. For each meta-analysis, we will estimate the effect size of a treatment through the random-effect model and the fixed-effect model, and we will evaluate between-study heterogeneity (Cochrane’s Q and I2statistics) and small-study effect (Egger’s test); we will also estimate the evidence of excess significance bias. Evidence of each treatment will be graded according to prespecified criteria. Methodological quality of each meta-analysis will be evaluated by using Assessment of Multiple Systematic Reviews 2. The corrected cover area method will be used to assess the impact of overlap in reviews on the findings of the umbrella review.Ethics and disseminationWe will present the results of the umbrella review at conferences and publish the final report in a peer-reviewed journal. The umbrella review does not require ethical approval.PROSPERO registration numberCRD42019140702.

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Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-024886 ◽

2019 ◽

Vol 9 (6) ◽

pp. e024886 ◽

Cited By ~ 24

Author(s):

Klaus Munkholm ◽

Asger Sand Paludan-Müller ◽

Kim Boesen

Keyword(s):

Systematic Review ◽

Clinical Study ◽

Effect Size ◽

Meta Analysis ◽

Evidence Base ◽

Risk Of Bias ◽

Depression Symptom ◽

Meta Analyses ◽

The Impact ◽

Clinical Study Reports

ObjectivesTo investigate whether the conclusion of a recent systematic review and network meta-analysis (Ciprianiet al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DesignReanalysis of a systematic review, with meta-analyses.Data sources522 trials (116 477 participants) as reported in the systematic review by Ciprianiet aland clinical study reports for 19 of these trials.AnalysisWe used the Cochrane Handbook’s risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.ResultsSeveral methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Ciprianiet al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a ‘placebo run-in’ study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p<0.0001). The outcome data reported by Ciprianiet aldiffered from the clinical study reports in 12 (63%) of 19 trials. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of the evidence and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton depression rating scale (range 0–52 points) was 1.97 points (95% CI 1.74 to 2.21).ConclusionsThe evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.

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