Background The management of cancer-related pain primarily relies on opioid analgesics, yet their use is frequently complicated by adverse effects and inadequate pain relief at higher doses. Objectives To assess the effectiveness and safety of adjunctive medications in reducing opioid requirements and improving pain management in patients with cancer-related pain. Methods A comprehensive literature search was performed in PubMed, Embase, and the Cochrane Library up to June 2024, encompassing all relevant records. Studies were included if they were randomized controlled trials (RCTs) or observational studies that compared the efficacy of combined adjuvant therapy with monotherapy using opioid analgesics for the management of cancer-related pain in adults and reported at least one pertinent outcome measure. Results This analysis included 13 studies (10 RCTs, n = 711; 3 retrospective studies, n = 314) evaluating adjunctive therapies including NSAIDs, anticonvulsants, antidepressants, and corticosteroids. Combination therapy significantly reduced daily opioid consumption versus monotherapy ([MD] −18.84 mg; 95% CI −28.19 to −9.52; P < 0.0001), with significant reductions specifically for NSAIDs (MD −17.27; 95% CI −30.26 to −4.27; P = 0.009) and anticonvulsants (MD −28.02; 95% CI −47.42 to −8.62; P = 0.005). Adjunctive therapy also significantly improved pain scores with NSAIDs (MD −0.79; 95% CI −0.97 to −0.62; P < 0.00001), dexamethasone (MD −1.43; 95% CI −2.23 to −0.63; P = 0.0004), and anticonvulsants (MD −0.23; 95% CI −0.42 to −0.03; P = 0.02). NSAIDs and antidepressants reduced dizziness (OR 0.34; 95% CI 0.19–0.59; P = 0.0002), while anticonvulsants increased its risk (OR 3.55; 95% CI 1.98–6.39; P < 0.0001). NSAIDs were associated with lower drowsiness (OR 0.28; 95% CI 0.13–0.57; P = 0.0005), whereas anticonvulsants and antidepressants increased drowsiness incidence (OR 3.49; 95% CI 2.02–6.01; P < 0.00001). No significant differences were observed in nausea/vomiting (OR 0.80; P = 0.19) or constipation (OR 0.73; P = 0.53). Meta-analysis of safety outcomes revealed no significant increase in the risk of serious adverse events with combination therapy compared to opioid monotherapy. Discussion The findings indicate that combined adjuvant therapy exhibits favorable efficacy and safety profiles in the management of cancer pain. Nevertheless, the selection of drug combinations requires an individualized approach. Future research should focus on further exploring optimized combination strategies to enhance the therapeutic effect. Conclusion The findings indicate that combined adjuvant therapy exhibits favorable efficacy and safety profiles in the management of cancer pain.

The role of combined adjuvant therapeutic drugs in modulating opioid dosage and pain status in cancer patients: a systematic review and meta-analysis

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发表日期：

2025年10月11日

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Xiao Zhang,
Da-Sheng Dang,
Xue Sun,
Ye Kang

摘要

Background

The management of cancer-related pain primarily relies on opioid analgesics, yet their use is frequently complicated by adverse effects and inadequate pain relief at higher doses.

Objectives

To assess the effectiveness and safety of adjunctive medications in reducing opioid requirements and improving pain management in patients with cancer-related pain.

Methods

A comprehensive literature search was performed in PubMed, Embase, and the Cochrane Library up to June 2024, encompassing all relevant records. Studies were included if they were randomized controlled trials (RCTs) or observational studies that compared the efficacy of combined adjuvant therapy with monotherapy using opioid analgesics for the management of cancer-related pain in adults and reported at least one pertinent outcome measure.

Results

This analysis included 13 studies (10 RCTs, n = 711; 3 retrospective studies, n = 314) evaluating adjunctive therapies including NSAIDs, anticonvulsants, antidepressants, and corticosteroids. Combination therapy significantly reduced daily opioid consumption versus monotherapy ([MD] −18.84 mg; 95% CI −28.19 to −9.52; P < 0.0001), with significant reductions specifically for NSAIDs (MD −17.27; 95% CI −30.26 to −4.27; P = 0.009) and anticonvulsants (MD −28.02; 95% CI −47.42 to −8.62; P = 0.005). Adjunctive therapy also significantly improved pain scores with NSAIDs (MD −0.79; 95% CI −0.97 to −0.62; P < 0.00001), dexamethasone (MD −1.43; 95% CI −2.23 to −0.63; P = 0.0004), and anticonvulsants (MD −0.23; 95% CI −0.42 to −0.03; P = 0.02). NSAIDs and antidepressants reduced dizziness (OR 0.34; 95% CI 0.19–0.59; P = 0.0002), while anticonvulsants increased its risk (OR 3.55; 95% CI 1.98–6.39; P < 0.0001). NSAIDs were associated with lower drowsiness (OR 0.28; 95% CI 0.13–0.57; P = 0.0005), whereas anticonvulsants and antidepressants increased drowsiness incidence (OR 3.49; 95% CI 2.02–6.01; P < 0.00001). No significant differences were observed in nausea/vomiting (OR 0.80; P = 0.19) or constipation (OR 0.73; P = 0.53). Meta-analysis of safety outcomes revealed no significant increase in the risk of serious adverse events with combination therapy compared to opioid monotherapy.

Discussion

The findings indicate that combined adjuvant therapy exhibits favorable efficacy and safety profiles in the management of cancer pain. Nevertheless, the selection of drug combinations requires an individualized approach. Future research should focus on further exploring optimized combination strategies to enhance the therapeutic effect.

Conclusion

The findings indicate that combined adjuvant therapy exhibits favorable efficacy and safety profiles in the management of cancer pain.