1 Academic Unit of Palliative Care, Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK.
2 Academic Unit of Health Economics, Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK.
Palliat Med. 2018 Jan;32(1):276-286. doi: 10.1177/0269216317711826. Epub 2017 Jun 12.
Combining antidepressant or antiepileptic drugs with opioids has resulted in increased pain relief when used for neuropathic pain in non-cancer conditions. However, evidence to support their effectiveness in cancer pain is lacking.
To determine if there is additional benefit when opioids are combined with antidepressant or antiepileptic drugs for cancer pain.
Systematic review and meta-analysis. Randomised control trials comparing opioid analgesia in combination with antidepressant or antiepileptic drugs versus opioid monotherapy were sought. Data on pain and adverse events were extracted. Data were pooled using DerSimonian-Laird random-effects meta-analyses, and heterogeneity was assessed.
Seven randomised controlled trials that randomised 605 patients were included in the review. Patients' pain was described as neuropathic cancer pain, cancer bone pain and non-specific cancer pain. Four randomised controlled trials were included in the meta-analysis in which opioid in combination with either gabapentin or pregabalin was compared with opioid monotherapy. The pooled standardised mean difference was 0.16 (95% confidence interval, -0.19, 0.51) showing no significant difference in pain relief between the groups. Adverse events were more frequent in the combination arms. Data on amitriptyline, fluvoxamine and phenytoin were inconclusive.
Combining opioid analgesia with gabapentinoids did not significantly improve pain relief in patients with tumour-related cancer pain compared with opioid monotherapy. Due to the heterogeneity of patient samples, benefit in patients with definite neuropathic cancer pain cannot be excluded. Clinicians should balance the small likelihood of benefit in patients with tumour-related cancer pain against the increased risk of adverse effects of combination therapy.
在非癌症情况下，将抗抑郁药或抗癫痫药与阿片类药物联合使用可缓解神经病理性疼痛，从而提高疼痛缓解率。然而，针对癌症疼痛，目前缺乏相关证据。
确定在癌症疼痛中，阿片类药物与抗抑郁药或抗癫痫药联合使用是否能带来额外的益处。
系统评价和荟萃分析。我们检索了比较阿片类药物联合抗抑郁药或抗癫痫药与阿片类药物单药治疗的随机对照试验。提取疼痛和不良事件数据。使用 DerSimonian-Laird 随机效应荟萃分析汇总数据，并评估异质性。
共纳入了 7 项随机对照试验，这些试验共纳入了 605 例患者。患者的疼痛描述为神经病理性癌症疼痛、癌症骨痛和非特异性癌症疼痛。其中 4 项随机对照试验纳入荟萃分析，比较了阿片类药物联合加巴喷丁或普瑞巴林与阿片类药物单药治疗的效果。合并后的标准化均数差值为 0.16（95%置信区间，-0.19，0.51），表明两组之间的疼痛缓解无显著差异。联合组的不良事件更常见。关于阿米替林、氟伏沙明和苯妥英的数据尚无定论。
与阿片类药物单药治疗相比，阿片类药物联合加巴喷丁类药物并不能显著改善肿瘤相关性癌症疼痛患者的疼痛缓解。由于患者样本的异质性，不能排除联合治疗对明确的神经病理性癌症疼痛患者有获益的可能性。临床医生应权衡肿瘤相关性癌症疼痛患者获益的可能性较小与联合治疗不良反应风险增加之间的利弊。
