1. 2025;28;1-10Pregabalin Combined With Opioids for Managing Neuropathic Pain in Patients With Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials
   Systematic Review
   Chuanbing Wen, MD, Maoying Wang, MS, Maotong Liu, MS, Chenyu Zhu, MS, Jinlong Zhao, MS, Qing Jiang, MS, RuRong Wang, MD, PhD, Jun Li, MD, PhD, and Li Song, MD, PhD.

BACKGROUND: Cancer-related neuropathic pain significantly affects patients’ quality of life. Despite existing treatments, pain control remains inadequate for many of these patients. There is a lack of strong evidence for the efficacy of the combination of pregabalin, which is often used to treat neuropathic pain, and opioids for treating cancer-related neuropathic pain.

OBJECTIVE: This study aimed to evaluate the analgesic effects and safety of pregabalin combined with opioids for managing cancer-related neuropathic pain through high-quality evidence analysis.

STUDY DESIGN: A systematic review and meta-analysis of pregabalin combined with opioids for cancer-related neuropathic pain.

METHODS: We systematically searched the PubMed, Web of Science, Embase, Cochrane Library and Cochrane Central Register of Controlled Trials databases from their inception through October 5, 2023. Two reviewers independently selected studies and extracted articles that met the inclusion and exclusion criteria. Quality assessments of the included studies were performed using the modified Cochrane Collaboration tool; data analysis was performed using RevMan 5.4 (The Nordic Cochrane Centre for The Cochrane Collaboration).

RESULTS: A total of 8 studies were included in our qualitative synthesis, and 6 studies were included in the meta-analysis (6 studies with 757 patients, including 342 in the experimental group and 415 in the control group). The results showed a significant difference between the pregabalin combined with opioids group and the opioids alone group in terms of Numeric Rating Scale (NRS-11) pain scores (weighted mean difference [WMD] = -1.00; 95% CI, -1.29 to -0.70; P < 0.001). However, no significant difference in the NRS-11 score was observed between the pregabalin combined with opioids group and active comparator combined with opioids group (WMD = -0.47; 95% CI, -1.05 to 0.11; P = 0.11). There was a significant difference between the pregabalin combined with opioids group and the active comparator combined with opioids group in terms of extra morphine milligram equivalents (relative risk [RR] = 0.37; 95% CI, 0.20 to 0.70; P = 0.002). No significant difference was observed in quality of life (WMD = -2.01; 95% CI, -5.29 to 1.27; P = 0.23). In general, the frequency of adverse events in the pregabalin combined with opioids group was greater than that in the opioids alone group, but the frequency of adverse events between the pregabalin combined with opioids group and the active comparator combined with opioids group was unclear.

LIMITATIONS: The limited number of articles and sample size are the limitations of this meta-analysis

CONCLUSIONS: Pregabalin combined with opioids reduces cancer-related neuropathic pain but increases dizziness, somnolence, and peripheral edema, thus supporting its use in the clinic for treating cancer-related neuropathic pain. However, further high-quality randomized controlled trials are needed to confirm these findings.

KEY WORDS: Pregabalin, cancer pain, meta-analysis, systematic review