University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK Regional Medical Affairs, Lilly Deutschland GmbH, Bad Homburg, Germany Unidad de Neurología, Clínica Creu Blanca, Barcelona, Spain Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität, München, Germany INSERM U987 Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, Boulogne Billancourt, France Sapienza University, Department of Neurology & Psychiatry, Roma, Italy Lilly Research Laboratories, Indianapolis, IN, USA Zentrum für Anästhesiologie, Intensivmedizin, Schmerztherapie & Palliativmedizin, Benedictus Krankenhaus, Tutzing & Klinik für Anästhesiologie, Technische Universität München, Germany.
Pain. 2013 Dec;154(12):2616-2625. doi: 10.1016/j.pain.2013.05.043. Epub 2013 May 31.
This multicentre, double-blind, parallel-group study in diabetic peripheral neuropathic pain addressed whether, in patients not responding to standard doses of duloxetine or pregabalin, combining both medications is superior to increasing each drug to its maximum recommended dose. For initial 8-week therapy, either 60 mg/day duloxetine (groups 1, 2) or 300 mg/day pregabalin (groups 3, 4) was given. Thereafter, in the 8-week combination/high-dose therapy period, only nonresponders received 120 mg/day duloxetine (group 1), a combination of 60 mg/day duloxetine and 300 mg/day pregabalin (groups 2, 3), or 600 mg/day pregabalin (group 4). Primary outcome (Brief Pain Inventory Modified Short Form [BPI-MSF] 24-hour average pain change after combination/high-dose therapy) was analyzed comparing combination (groups 2, 3 pooled) with high-dose monotherapy (groups 1, 4 pooled). Secondary end points included response rates, BPI-MSF severity items, and comparison of duloxetine and pregabalin in BPI-MSF average pain. Eight hundred four patients were evaluated for initial therapy and 339 for combination/high-dose therapy. There were no significant differences between combination and high-dose monotherapy regarding BPI-MSF average pain (mean change: combination: -2.35; high-dose monotherapy: -2.16; P = 0.370) and most secondary end points, which, however, consistently favoured combination therapy. Fifty-percent response rates were 52.1% for combination and 39.3% for high-dose monotherapy (P = 0.068). In exploratory analyses of the initial 8-week therapy uncorrected for multiple comparisons, 60 mg/day duloxetine was found superior to 300 mg/day pregabalin (P < 0.001). Both drugs and their combination were well tolerated. Although not significantly superior to high-dose monotherapy, combination therapy was considered to be effective, safe, and well tolerated.
这项多中心、双盲、平行组研究针对的是糖尿病周围神经性疼痛患者，评估在标准剂量度洛西汀或普瑞巴林治疗无反应的患者中，联合使用这两种药物是否优于将每种药物增加到最大推荐剂量。在最初的 8 周治疗中，给予 60 mg/天度洛西汀（第 1、2 组）或 300 mg/天普瑞巴林（第 3、4 组）。此后，在 8 周联合/高剂量治疗期间，仅对无反应者给予 120 mg/天度洛西汀（第 1 组），联合使用 60 mg/天度洛西汀和 300 mg/天普瑞巴林（第 2、3 组）或 600 mg/天普瑞巴林（第 4 组）。主要结局（24 小时平均疼痛变化后的简明疼痛量表修订短表[BPI-MSF]）通过比较联合治疗（第 2、3 组合并）与高剂量单药治疗（第 1、4 组合并）进行分析。次要终点包括反应率、BPI-MSF 严重程度项目以及 BPI-MSF 平均疼痛中度洛西汀和普瑞巴林的比较。804 例患者接受初始治疗，339 例患者接受联合/高剂量治疗。联合治疗与高剂量单药治疗在 BPI-MSF 平均疼痛（平均变化：联合治疗：-2.35；高剂量单药治疗：-2.16；P = 0.370）和大多数次要终点方面无显著差异，但联合治疗始终更有利。联合治疗的 50%反应率为 52.1%，高剂量单药治疗为 39.3%（P = 0.068）。在未对多次比较进行校正的初始 8 周治疗的探索性分析中，发现 60 mg/天度洛西汀优于 300 mg/天普瑞巴林（P < 0.001）。两种药物及其联合治疗均具有良好的耐受性。虽然联合治疗与高剂量单药治疗相比无显著优势，但被认为是有效、安全且耐受良好的。
