Effective maNagement of depression among patients witH cANCEr (ENHANCE): A hybrid systematic review and (attempted) network meta-analysis of randomized controlled trials

Background: Optimal intervention(s) for depression among people with cancer are unknown, as all available approaches have not been compared. This hybrid systematic review aimed to identify the most effective and acceptable intervention(s) using network meta-analysis (NMA). Methods: Randomized controlled trials (RCTs) of depression interventions among adults with cancer experiencing depressive symptoms were identified from database searches for previous systematic reviews and more recent RCTs. Screening, data extraction, Risk of Bias (RoB2) and Research Integrity Assessment (RIA; for descriptive rather than screening purposes) were performed independently, in duplicate. Primary outcomes were change in depressive symptoms (efficacy/effectiveness) and the rate who discontinued (acceptability). As the planned NMA was not appropriate, a narrative critical synthesis was performed. Findings: 70 RCTs (6831 participants) were included (43 psychotherapy, 14 pharmacotherapy, 8 complementary and alternative medicine, 7 collaborative care, 4 exercise, and 3 combination therapy interventions). No significant differences regarding acceptability were evident. Reliable efficacy/effectiveness comparisons using NMA were not possible due to RoB (44.3 % Some concerns, 54.3 % High RoB). Only 10 RCTs had no integrity concerns. Integrity issues included no pre-registration (n = 56/80 %), insufficient reporting on randomisation (n = 27/38.6 %) and ethics (n = 32/40 %), and questionable effect sizes (n = 26/37 %). The most reliable evidence was for collaborative care. Conclusions: The literature on depression interventions for people with cancer is at RoB, pointing to an urgent need for high-quality research. Until such evidence is available, treatment decisions should continue to be based on evidence from other patient groups and clinical expertise, though there is some evidence that collaborative care is effective. Systematic review registration: PROSPERO CRD42021290145 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=290145