Comparative efficacy and acceptability of non-pharmacological and pharmacological treatments in post-stroke depression: protocol for a systematic review and network meta-analysis.

Abstract

Depression is a common complication of stroke that adversely affects functional recovery. Although a wide range of pharmacological and non-pharmacological interventions are used in clinical practice, evidence regarding their comparative efficacy and acceptability remains inconclusive. Therefore, we will conduct the first systematic review and network meta-analysis (NMA) to compare and rank available interventions for post-stroke depression (PSD). The findings will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. In this systematic review and network meta-analysis, we will search PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform from database inception to 1 September 2025 to identify published and unpublished randomised controlled trials (RCTs). We will include studies comparing pharmacological and non-pharmacological treatments, or any control conditions as monotherapy for the treatment of patients with PSD. We will assess the certainty of evidence using the Confidence in Network Meta-Analysis framework. The primary outcomes will be the change score on depression scales from baseline to the end of treatment (efficacy) and all-cause discontinuation (acceptability). Secondary outcomes will include quality of life, cognitive and neurological function scores, anxiety and sleep quality. Two reviewers will independently screen and select eligible studies based on predefined inclusion and exclusion criteria. Risk of bias in all RCTs included in the NMA will be assessed using the revised Cochrane Risk of Bias tool (RoB 2). A frequentist NMA will be conducted in Stata and R. Meta-regression and sensitivity analyses will be performed to assess robustness. This NMA does not need ethical approval, as the data used here are based on aggregated data in the public domain. Findings from the analysis will provide an overview and information on the relative efficacy and acceptability of non-pharmacological and pharmacological treatments in PSD. The results will be disseminated through peer-reviewed publication. CRD420251136670.