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Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis

Por: Türkmen · C. · Sacu · S. · Furukawa · Y. · de Cates · A. N. · Schoevers · R. A. · Kamphuis · J. · Chevance · A. · Weisz · J. R. · Emslie · G. J. · Strawn · J. R. · Hetrick · S. E. · Efthimiou · O. · Salanti · G. · van Dalfsen · J. H. · Furukawa · T. A. · Cipriani · A.
Introduction

Major depressive disorder (MDD) is among the most common psychiatric disorders in children and adolescents. While previous meta-analyses have synthesised evidence on the efficacy and acceptability of newer-generation antidepressants in this population, specific adverse events (AEs) remain poorly characterised. This is of high clinical importance, as AEs are burdensome for patients, can reduce treatment adherence and lead to discontinuation. Here, we present a protocol for a network meta-analysis designed to evaluate the specific AE profile and comparative tolerability of newer-generation antidepressants in children and adolescents with MDD.

Methods and analysis

The planned study will include double-blind randomised controlled trials that compared one active drug with another and/or placebo for the acute treatment of MDD in children and adolescents. The following antidepressants will be considered: agomelatine, alaproclate, bupropion, citalopram, desvenlafaxine, duloxetine, edivoxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, vilazodone and vortioxetine. The primary outcomes will include the number of patients experiencing at least one AE, specific non-serious AEs, serious AEs (eg, suicidal ideation) and AEs leading to treatment discontinuation. Published and unpublished studies will be retrieved through a systematic search in the following databases: PubMed, Embase, Cochrane Library (including the Cochrane Central Register of Controlled Trials), Web of Science Core Collection, PsycInfo and regulatory agencies’ registries. Study selection and data extraction will be performed independently by two reviewers. For each outcome, a network meta-analysis will be performed to synthesise all evidence. Consistency will be assessed through local and global methods, and the confidence in the evidence will be evaluated using the Confidence in Network Meta-Analysis web application. All analyses will be conducted in the R software.

Ethics and dissemination

The planned review does not require ethical approval. The findings will be published in a peer-reviewed journal and may be presented at international conferences.

PROSPERO registration number

CRD420251011399.

Deconstructing resuscitation training for healthcare providers: a protocol for a component network meta-analysis

Introduction

The necessity of enhancing resuscitation training has been encouraged by The International Liaison Committee on Resuscitation and the American Heart Association to reduce mortality, disability and healthcare costs. Resuscitation training is a complicated approach that encompasses various components and their mixture. It is essential to identify the most effective of these components and their combinations, to measure the corresponding effect size and to understand which participant groups may enjoy the greatest advantage.

Methods and analysis

We will systematically search 12 databases and two clinical trial registries for randomised controlled trials (RCTs) that examine different resuscitation training methods from inception to April 2025. The analysis will be carried out using the standard network meta-analysis and component network meta-analysis models. Resuscitation skills of staff will be the primary outcome of this analysis. Paired reviewers will independently screen and extract data. A consensus will be sought with the principal investigators to resolve any disagreements that cannot be achieved through regular meetings. Each intervention in each RCT will be decomposed according to its constituent components, such as delivery method, interactivity, teamwork, digitalisation and type of simulator. The analysis will be conducted using the frequentist and bayesian approach in the R environment. RoB V.2.0 and Confidence in Network Meta-Analysis will, respectively, be used to assess the risk of bias and the certainty of the evidence.

Ethics and dissemination

As we will use only aggregated secondary data without individual identities, ethical approval is not required. Results of this review will be shared through a peer-reviewed publication and presentation of papers at any relevant conferences.

PROSPERO registration number

CRD42024532878

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