Effective maNagement of depression among patients witH cANCEr (ENHANCE): a protocol for a hybrid systematic review and network meta-analysis of randomized controlled trials of interventions for depressive symptoms.

Background: Depression is common among patients with cancer and is associated with lower treatment participation, lower satisfaction with care, poorer quality of life, greater symptom burden, and higher healthcare costs. Various types of interventions (e.g., pharmacological, psychotherapy) are used for the treatment of depression. However, evidence for these among patients with cancer is limited. Furthermore, the relative effectiveness and acceptability of different approaches is unknown because a direct comparison between all available treatments has not been carried out. We will address this by conducting a network meta-analysis (NMA) of interventions for depression among people with cancer using a hybrid overview of reviews and systematic review methodology. Methods: We will search for and extract data from systematic reviews of randomised controlled trials (RCTs) of depression interventions for patients with cancer from inception, before performing a supplemental search for more recent RCTs. We will include RCTs comparing pharmacological, psychotherapy, exercise, combination therapy, collaborative care, or complementary and alternative medicine interventions with pill placebo, no treatment, waitlist, treatment as usual, or minimal treatment control groups, or directly in head-to-head trials, among adults who have a current or previous diagnosis of cancer and elevated depressive symptoms (scores above a cut-off on validated scales or meeting diagnostic criteria). Our primary outcomes will be change in depressive symptoms (standardised mean difference) and intervention acceptability (% who withdrew). Our secondary outcomes will be 6-month change in depressive symptoms, health-related quality of life, adverse events and mortality. We will independently screen for eligibility, extract data, and assess risk of bias using the RoB2 tool. We will use frequentist random-effects multivariate NMA in Stata, Rankograms and surface under the cumulative ranking curves to synthesize evidence and obtain a ranking of intervention groups. We will explore heterogeneity and inconsistency using local and global measures and evaluate the credibility of results using the Confidence in NEtwork Meta-Analysis (CINeMA) framework. Discussion: Our findings will provide the best available evidence for managing depression among patients with cancer. Such information will help to inform clinical guidelines, evidence-based treatment decisions and future research by identifying gaps in the current literature. Systematic review registration: Submitted to PROSPERO (record number: 290145), awaiting registration