How trustworthy and applicable is the evidence from systematic reviews of depression treatments: Protocol for systematic examination

Background: Depression is a common mental disorder significantly impacting daily functioning. Standard treatments include drugs, psychotherapies, or a combination of both. Treatment selection relies on scientific evidence, though the trustworthiness and applicability of this evidence can vary. Objectives: This protocol presents a method to evaluate evidence from systematic reviews for pharmacological and psychological treatments for depression, focusing on trustworthiness and applicability structured into five components: quality of conduct and reporting, risk of bias, spin in abstract conclusions, robustness of meta-analytical results, heterogeneity and clinical diversity. Methods: We will conduct a systematic search of systematic reviews in MEDLINE, Embase, PsycInfo, and Cochrane Database of Systematic Reviews. Our focus will be on systematic reviews of first-line treatments for depression in adults, including antidepressants, psychotherapy, or combined treatments, compared to either active or inactive comparators. We will extract information needed for a comprehensive methodological evaluation using qualitative tools, including AMSTAR 2, ROBIS, Conflict-of-Interest assessment, Referencing Framework for SRs, Spin Measure, and heterogeneity exploration assessment. For quantitative analyses, such as Fragility Index, Ellipse of Insignificance, Region of Attainable Redaction, GRIM test, Leave-N-Out analysis, and prediction intervals, we will select and recalculate two meta-analyses per review. We define a set of outcomes to enable practical and intuitive interpretation of these analyses’ results. Descriptive statistics, non-parametric statistical tests, and narrative summaries will be used to synthesize and compare outcomes across several pre-specified subgroups. Expected outcomes: We expect these analyses to provide an enhanced perspective on the practice of evidence synthesis in the field of mental health, offer methodological guidance for future systematic reviews and meta-analyses, and contribute to improved informed decision-making by clinicians and patients. OSF registration: osf.io/7f9cj and osf.io/ynejs