A meta-analysis of the efficacy of four antidepressants combined with common opioid analgesics in the treatment of cancer-related neuropathic pain

Introduction The aim of the study was to conduct a meta-analysis evaluating the efficacy of four antidepressants combined with commonly used opioid analgesics for the treatment of cancer-related neuropathic pain. Material and methods A comprehensive search of Chinese and English databases was performed to identify relevant studies investigating the combination of duloxetine, venlafaxine, amitriptyline, or fluoxetine with opioid analgesics in managing cancer-related neuropathic pain. Results Seventeen studies published between 2005 and 2024, involving 1,636 patients, were included. Among them, ten were randomized controlled trials (RCTs) and seven were non-RCTs. Six studies reported opioid consumption, and meta-analysis of continuous data showed significantly lower opioid use in the treatment group compared to controls (OR = –2.99, 95% CI: –4.51 to –1.48, Z = –3.86, p < 0.01). Eleven studies assessed pain scores, with pooled results indicating significantly greater pain reduction in the treatment group (OR = –1.03, 95% CI: –1.44 to –0.62, Z = –4.94, p < 0.01). Eight studies reported depression scores, revealing significantly lower depression levels in the treatment group (OR = –2.72, 95% CI: –3.74 to –1.69, Z = –5.19, p < 0.01). Eight studies reported quality of life, and a meta-analysis of continuous variables showed no significant difference in the quality of life scores between the two groups (OR = –1.01, 95% CI: –2.30 to 0.28, Z = –1.54, p = 0.12). Eight studies reported treatment efficacy, and a meta-analysis of binary variables revealed that the treatment group had significantly higher efficacy than the control group (OR = 0.72, 95% CI: 0.29 to 1.15, Z = 3.27, p < 0.01). Five studies reported adverse reactions, with no significant difference observed between groups (OR = 0.14, 95% CI: –0.41 to 0.68, Z = 0.49, p = 0.62). Funnel plot analysis suggested publication bias in pain score outcomes, potentially due to variability in pain assessment methods and timing. Conclusions Combining duloxetine, venlafaxine, amitriptyline, or fluoxetine with commonly used opioid analgesics effectively alleviates cancer-related neuropathic pain with minimal adverse effects. This therapeutic approach offers flexible application in clinical practice.