Holbech Jakob Vormstrup, Jung Anne, Jonsson Torsten, Wanning Mette, Bredahl Claus, Bach Flemming W
Department of Neurology, Odense University Hospital, Odense.
Medicinsk Fælles Ambulatorium, Holbaek Hospital.
J Pain Res. 2017 Jun 26;10:1467-1475. doi: 10.2147/JPR.S138099. eCollection 2017.
Current Danish treatment algorithms for pharmacological treatment of neuropathic pain (NeP) are tricyclic antidepressants (TCA), gabapentin and pregabalin as first-line treatment for the most common NeP conditions. Many patients have insufficient pain relief on monotherapy, but combination therapy had not been included in guidelines until recently. Based on clinical empiricism and scientific evidence, a Delphi consensus process provided a consolidated guidance on pharmacological combination treatment of NeP.
A two-round virtual internet-based Delphi process with 6 Danish pain specialists was undertaken. In the first round, questions were answered individually and anonymously, whereas in the second round, the panel openly discussed first round's summary of outcomes. Combinations of pharmacological pain treatments, that is, pregabalin/gabapentin, TCAs, serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors, opioids, other antiepileptics and cutaneous patches, were assessed based on both scientific and clinical practice experiences. The Centers for Disease Control and Prevention (CDC) grading system was used for evidence rating.
Combination of pregabalin/gabapentin with TCA is useful in patients who do not gain sufficient pain relief or tolerate either drug in high doses, or to improve sleep disturbance. Also, combination of pregabalin/gabapentin and SNRIs is reasonably well documented and experienced by some experts to result in sufficient pain relief and fewer side effects than monotherapy. Good evidence on efficacy was found for the combination of pregabalin/gabapentin or TCAs and opioids, which was also frequently used in clinical practice. The evidence for combining TCAs and SNRIs is insufficient, although sometimes used in clinical practice despite the risk of serotonin syndrome. For localized NeP, combination therapy with cutaneous patches should be considered. There was insufficient scientific evidence for any pharmacologic combination therapies with selective serotonin reuptake inhibitors - as well as for other potential combinations.
The study revealed that combination therapy is widely used in clinical practice and supported by some scientific evidence. However, further studies are needed.
丹麦目前用于神经性疼痛（NeP）药物治疗的算法是，三环类抗抑郁药（TCA）、加巴喷丁和普瑞巴林作为最常见NeP病症的一线治疗药物。许多患者单药治疗时疼痛缓解不足，但直到最近联合治疗才被纳入指南。基于临床经验和科学证据，德尔菲共识过程为NeP的药物联合治疗提供了综合指导。
对6名丹麦疼痛专家进行了两轮基于互联网的虚拟德尔菲过程。在第一轮中，问题由专家单独且匿名回答，而在第二轮中，专家小组公开讨论了第一轮的结果总结。基于科学和临床实践经验，对药物性疼痛治疗的组合，即普瑞巴林/加巴喷丁、三环类抗抑郁药、5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRI）、选择性5-羟色胺再摄取抑制剂、阿片类药物、其他抗癫痫药和皮肤贴片进行了评估。采用美国疾病控制与预防中心（CDC）分级系统进行证据评级。
普瑞巴林/加巴喷丁与三环类抗抑郁药联合使用，对疼痛缓解不足或无法耐受高剂量单一药物治疗的患者有用，或有助于改善睡眠障碍。此外，普瑞巴林/加巴喷丁与5-羟色胺-去甲肾上腺素再摄取抑制剂联合使用有一定的文献记载，一些专家认为与单药治疗相比，这种联合用药能带来足够的疼痛缓解且副作用更少。普瑞巴林/加巴喷丁或三环类抗抑郁药与阿片类药物联合使用的疗效有充分证据，在临床实践中也经常使用。三环类抗抑郁药与5-羟色胺-去甲肾上腺素再摄取抑制剂联合使用的证据不足，尽管存在5-羟色胺综合征风险，但在临床实践中有时仍会使用。对于局限性NeP，应考虑采用皮肤贴片联合治疗。对于选择性5-羟色胺再摄取抑制剂的任何药物联合治疗以及其他潜在联合治疗，均缺乏充分的科学证据。
该研究表明联合治疗在临床实践中广泛应用且有一些科学证据支持。然而，仍需进一步研究。
