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SYSTEMATIC REVIEW/META-ANALYSIS
A meta-analysis of the efficacy of four antidepressants combined with common opioid analgesics in the treatment of cancer-related neuropathic pain
1
Department of Pain, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China
Submission date: 2025-03-13
Final revision date: 2025-06-27
Acceptance date: 2025-07-12
Online publication date: 2025-08-04
Corresponding author
Yi Yi
Department of Pain Hunan Provincial People’s Hospital/ (The First Affiliated Hospital of Hunan Normal University) Changsha 410016, China
Department of Pain Hunan Provincial People’s Hospital/ (The First Affiliated Hospital of Hunan Normal University) Changsha 410016, China
KEYWORDS
TOPICS
ABSTRACT
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.
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.
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