Abstract
BACKGROUND: Depression is are often insufficiently managed in cancer patients globally. To address this, we conducted a comprehensive systematic review and network meta-analysis to evaluate and compare the effectiveness of pharmacological and non-pharmacological interventions in alleviating depressive symptoms in adult cancer patients. METHODS: We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception until 31 July 2024, with an updated search conducted on 10 January 2025. Eligible studies were randomised controlled trials evaluating pharmacological or non-pharmacological interventions for depressive symptoms in adult patients with cancer (aged ≥18 years). Studies involving paediatric populations, lacking complete outcome data, or not reporting intervention outcomes were excluded. A Bayesian network meta-analysis was undertaken to compare the effectiveness of included interventions. The review protocol was prospectively registered in PROSPERO (CRD42023465056). FINDINGS: A total of 95 RCTs involving 17,260 participants were included. Several non-pharmacological interventions indicated potential benefit compared with usual care, notably massage and touch therapy (standardised mean difference [SMD]: -0.76, 95% CI: -1.37 to -0.16; low certainty), relaxation therapy (SMD: -0.59, 95% CI: -1.06 to -0.11; low certainty), psychotherapy (SMD: -0.43, 95% CI: -0.56 to -0.30; low certainty), and education and support of person with cancer (SMD: -0.30, 95% CI: -0.45 to -0.14; low certainty). Among pharmacological approaches, preliminary findings suggest the combination of mirtazapine and methylphenidate may offer benefits compared with placebo (SMD: -2.46, 95% CI: -4.24 to -0.70; low certainty). However, the overall evidence quality was low, reflecting substantial variability and limited data. INTERPRETATION: Non-pharmacological interventions such as massage, relaxation therapies, and psychotherapy show promise in alleviating depressive symptoms in cancer patients. Limited preliminary evidence also suggests possible benefits of combined pharmacological treatment (mirtazapine plus methylphenidate). More rigorous research is required to strengthen these findings and better inform clinical practice.