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Comparative efficacy and acceptability of antidepressants in the long-term treatment of major depression: protocol for a systematic review and networkmeta-analysis.

ABSTRACT: INTRODUCTION:Pharmacotherapy plays an important role in the treatment of major depression. At the initiation of antidepressant treatment, both improvement of symptoms in the short term and relapse prevention in the long term should be taken into account. However, there is insufficient evidence regarding the efficacy and the acceptability of continuation/maintenance treatments and the relative efficacy/acceptability of antidepressants. OBJECTIVE:We will conduct a pairwise meta-analysis and a network meta-analysis (NMA) to examine the relative efficacy, tolerability and acceptability of antidepressants in the long-term treatment of major depression. METHODS AND ANALYSIS:We will include double-blind randomised controlled trials comparing any of the following antidepressants, which we included in our previous NMA of the acute treatment for major depression, with placebo or with another active drug for long-term treatment of major depression: agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. Our primary outcomes will be sustained response and all-cause dropouts. We will include four types of designs that are used to investigate long-term treatment. We will conduct two main analyses. First, we will conduct a pairwise meta-analysis comparing all antidepressants versus placebo to investigate whether continuing antidepressants after achieving a positive response in the acute-phase treatment is beneficial and/or safe. Second, we will conduct an NMA to examine the comparative efficacy and acceptability of the drugs. We will use a novel approach that will combine the results of acute-phase treatment NMA with long-term treatment studies to include all related designs in the NMA. We will ensure the validity of combining different designs and our new approach by checking the distribution of important effect modifiers and consistency of network. ETHICS AND DISSEMINATION:This study did not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER:CRD42018114561; Pre-results.

SUBMITTER: Shinohara K

PROVIDER: S-EPMC6530313 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Comparative efficacy and acceptability of antidepressants in the long-term treatment of major depression: protocol for a systematic review and networkmeta-analysis.

Shinohara Kiyomi K Efthimiou Orestis O Ostinelli Edoardo G EG Tomlinson Anneka A Geddes John R JR Nierenberg Andrew A AA Ruhe Henricus G HG Furukawa Toshi A TA Cipriani Andrea A

BMJ open 20190519 5

<h4>Introduction</h4>Pharmacotherapy plays an important role in the treatment of major depression. At the initiation of antidepressant treatment, both improvement of symptoms in the short term and relapse prevention in the long term should be taken into account. However, there is insufficient evidence regarding the efficacy and the acceptability of continuation/maintenance treatments and the relative efficacy/acceptability of antidepressants.<h4>Objective</h4>We will conduct a pairwise meta-anal ...[more]

PMID: 31110100

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Project description:INTRODUCTION:Major depression is a leading cause of disability and has been associated with adverse effects in older persons. While many pharmacological and non-pharmacological interventions have been shown to be effective to address major depression in older persons, there has not been a meta-analysis that consolidates all the available interventions and compare the relative benefits of these available interventions. In this study, we aim to conduct a systematic review and network meta-analysis to compare the efficacy and acceptability of all the known pharmacological and non-pharmacological interventions for major depression in older persons. METHODS AND ANALYSIS:We will search Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials and references of other review articles for articles related to the keywords of 'randomised trial', 'major depression', 'older persons' and 'treatments'. Two reviewers will independently select the eligible articles. For each included article, the two reviewers will independently extract the data and assess the risk of bias using the Cochrane revised tool for risk of bias. Bayesian network meta-analyses will be conducted to pool the depression scores (based on standardised mean difference) and the all-cause discontinuation across all included studies. The ranking probabilities for all interventions will be estimated and the hierarchy of each intervention will be summarised as surface under the cumulative ranking curve (SUCRA). Meta-regression and sub-group analyses will also be performed to evaluate the effect of study-level covariates. The quality of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION:The results will be disseminated through conference presentations and peer-reviewed publications. They will provide the consolidated evidence to inform clinicians on the best choice of intervention to address major depression in older persons. PROSPERO REGISTRATION NUMBER:CRD42017075756.

Project description:IntroductionDepressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents.Methods and analysisWe will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings.DisseminationThis NMA will provide the most up to date and clinically useful information about the comparative efficacy and acceptability of antidepressants, psychological intervention and their combination in the acute treatment of children and adolescents with depressive disorder. This is the newest NMA and therefore these results are very important in terms of evidence-based medicine. The results will be disseminated through peer-reviewed publication.Protocol registrationPROSPERO CRD42015020841.

Project description:BackgroundAntidepressant medicines are used to manage symptoms of low back pain. The efficacy, acceptability, and safety of antidepressant medicines for low back pain (LBP) are not clear. We aimed to evaluate the efficacy, acceptability, and safety of antidepressant medicines for LBP.MethodsWe searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov , the EU Clinical Trials Register, and the WHO International Clinical Trial Registry Platform from inception to May 2020. We included published and trial registry reports of RCTs that allocated adult participants with LBP to receive an antidepressant medicine or a placebo medicine. Pairs of authors independently extracted data in duplicate. We extracted participant characteristics, study sample size, outcome values, and measures of variance for each outcome. We data using random-effects meta-analysis models and calculated estimates of effects and heterogeneity for each outcome. We formed judgments of confidence in the evidence in accordance with GRADE. We report our findings in accordance with the PRISMA statement. We prespecified all outcomes in a prospectively registered protocol. The primary outcomes were pain intensity and acceptability. We measured pain intensity at end-of-treatment on a 0-100 point scale and considered 10 points the minimal clinically important difference. We defined acceptability as the odds of stopping treatment for any reason.ResultsWe included 23 RCTs in this review. Data were available for pain in 17 trials and acceptability in 14 trials. Treatment with antidepressants decreased pain intensity by 4.33 points (95% CI - 6.15 to - 2.50) on a 0-100 scale, compared to placebo. Treatment with antidepressants increased the odds of stopping treatment for any reason (OR 1.27 [95% CI 1.03 to 1.56]), compared to placebo.ConclusionsTreatment of LBP with antidepressants is associated with small reductions in pain intensity and increased odds of stopping treatment for any reason, compared to placebo. The effect on pain is not clinically important. The effect on acceptability warrants consideration. These findings provide Level I evidence to guide clinicians in their use of antidepressants to treat LBP.Trial registrationWe prospectively registered the protocol for this systematic review on PROSPERO ( CRD42020149275 ).

Project description:INTRODUCTION:Although previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain unsolved by the aggregate data from those meta-analyses. Individual participant data meta-analysis (IPD-MA) enables exploration of the impacts of individual characteristics on treatment effects, allowing matching of treatments to specific subgroups of patients. We will perform an IPD-MA to assess the efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents. METHODS AND ANALYSIS:We will systematically search for all double-blind randomised controlled trials (RCTs) that have compared any new-generation antidepressant with placebo for the acute treatment of major depressive disorder in children and adolescents, in the following databases: PubMed, EMBASE, the Cochrane Library, PsycINFO, Web of Science, CINAHL, LILACS and ProQuest Dissertations. We will contact all corresponding authors of included RCTs and ask for their cooperation in this project by providing individual participant data from the original trials. The primary outcomes will include efficacy, measured as the mean change of depression symptoms by Children's Depression Rating Scale Revised (CDRS-R), and tolerability, measured as the proportion of patients who withdrew from the trials early due to adverse effects. The secondary outcomes will include response rates, remission rates, deterioration rate, all-cause discontinuation, suicidal-related outcomes and global functioning outcome. Using the raw de-identified study data, we will use mixed-effects logistic and linear regression models to perform the IPD-MAs. The risk of bias of included studies will be assessed using the Cochrane risk of bias tool. We will also detect the publication bias and effects of non-participation of eligible studies. DISSEMINATION:Ethical approval is not required given that informed consent has already been obtained from the patients by the trial investigators before the included trials were conducted. This study may have considerable implications for practice and help improve patient care. PROSPERO REGISTRATION NUMBER:CRD42016051657.

Dataset Information

Comparative efficacy and acceptability of antidepressants in the long-term treatment of major depression: protocol for a systematic review and networkmeta-analysis.

Publications

Comparative efficacy and acceptability of antidepressants in the long-term treatment of major depression: protocol for a systematic review and networkmeta-analysis.

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