Current practices in modelling dose-response relationships in network meta-analyses of depression treatments: a...

Dose can meaningfully affect the comparative effectiveness of depression treatments, yet how network meta-analyses (NMAs) in this field handle dose is not well characterised. We conducted a meta-research study to examine how current depression NMAs incorporate dosing information and identify methodological gaps in current practice.

Meta-research study following guidance for meta-epidemiological research and incorporating relevant elements of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020.

We searched PubMed, Embase, the Cochrane Library, PsycINFO, Web of Science and Scopus for NMAs published between January 2020 and May 2025.

NMAs comparing interventions, or different doses of a single intervention, in the context of depression-where an antidepressant was evaluated for depression-related indications and/or depressive symptoms were the primary clinical focus-and in which dose variation was incorporated into the evidence synthesis.

We extracted data on dose-handling strategies, analysis methods, statistical frameworks and reporting quality, and synthesised these narratively to characterise methodological practice across studies.

Twenty studies met inclusion criteria, evaluating pharmacologic interventions (n=11), non-pharmacologic interventions (n=7) or both (n=2). Dose handling varied substantially: in primary analyses, 50% treated dosages as separate nodes (split approach), 32% lumped doses together and only 15% used model-based methods incorporating dose-response relationships. Nine studies employed the R package MBNMAdose to conduct a model-based NMA for secondary analyses, primarily examining exercise interventions with varied dose-response functions. Reporting of priors, consistency assessments and justifications for dose categorisation or operationalisation was inconsistent.

Current depression NMAs demonstrate broad variability in handling dose-related heterogeneity, with dose-response modelling often absent or inconsistently applied-particularly for behavioural interventions lacking standardised dose metrics. Greater methodological clarity, practical guidance and reporting standards are needed to integrate dose-response modelling into NMAs of depression treatments, where both pharmacologic and behavioural interventions pose distinct dosing challenges.