度洛西汀及普瑞巴林：高剂量单药治疗还是联合治疗？以糖尿病周围神经痛患者为受试者的COMBO-DN多中心随机双盲平行组试验结果

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 60mg/day duloxetine (groups 1, 2) or 300mg/day pregabalin (groups 3, 4) was given. Thereafter, in the 8-week combination/high-dose therapy period, only nonresponders received 120mg/day duloxetine (group 1), a combination of 60mg/day duloxetine and 300mg/day pregabalin(groups 2, 3), or 600mg/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 betweencombination 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% forcombination and 39.3% for high-dose monotherapy (P=0.068). In exploratory analyses of the initial 8-week therapy uncorrected for multiple comparisons, 60mg/day duloxetine was found superior to 300mg/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.