Tanenberg Robert J, Clemow David B, Giaconia Joseph M, Risser Richard C
Division of Endocrinology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, U.S.A.
Lilly USA, LLC, Indianapolis, Indiana, U.S.A.
Pain Pract. 2014 Sep;14(7):640-8. doi: 10.1111/papr.12121. Epub 2013 Oct 24.
To examine the efficacy of duloxetine vs. pregabalin in the treatment for diabetic peripheral neuropathic pain (DPNP), comparing patient subgroups with and without concomitant antidepressant use.
This post hoc analysis assessed data from a randomized 12-week study that confirmed the noninferiority of duloxetine to pregabalin. In the previously published study, patients with DPNP with inadequate response to gabapentin were switched to duloxetine monotherapy, combination therapy of duloxetine plus gabapentin, or pregabalin monotherapy. Current, stable antidepressant use was allowed; 79 patients were concomitantly treated with antidepressants and 328 without antidepressants. In this post hoc analysis, improvement in the weekly mean of diary-based average daily pain ratings (numerical rating scale: 0-10) in antidepressant users and nonusers was analyzed using a longitudinal mixed-models repeated-measures (MMRM) analysis, including a test of the 3-way interaction (antidepressant subgroup by treatment by week) to assess whether the differences among treatment groups over 12 weeks differ between the antidepressant-use subgroups.
The 3-way interaction was significant (P = 0.035), demonstrating that treatment-group differences in pain reduction over time differ between the subgroups. Among patients without antidepressant use, patients treated with duloxetine had significantly greater pain reduction than pregabalin at Week 4 and at each successive week up to the 12-week endpoint (-2.8 for duloxetine and -2.1 for pregabalin; P = 0.031); patients treated with duloxetine plus gabapentin had greater pain reduction than pregabalin at Weeks 2, 3, 5, and 7 to 9 (P ≤ 0.05) but not at endpoint (-2.4; P = 0.222). Among concomitant antidepressant users, no treatment-group differences were found.
In patients with DPNP inadequately treated with gabapentin without the concomitant use of antidepressants, switching to duloxetine instead of pregabalin may provide better pain reduction. Conversely, in nonresponders to gabapentin who are concomitantly using an antidepressant, switching to duloxetine or pregabalin may provide similar pain reductions.
比较度洛西汀与普瑞巴林治疗糖尿病性周围神经病变性疼痛（DPNP）的疗效，并比较同时使用和未使用抗抑郁药的患者亚组情况。
本事后分析评估了一项为期12周的随机研究数据，该研究证实度洛西汀不劣于普瑞巴林。在先前发表的研究中，对加巴喷丁反应不足的DPNP患者被改为度洛西汀单药治疗、度洛西汀加加巴喷丁联合治疗或普瑞巴林单药治疗。允许患者持续稳定使用抗抑郁药；79例患者同时接受抗抑郁药治疗，328例未接受抗抑郁药治疗。在本事后分析中，使用纵向混合模型重复测量（MMRM）分析来分析使用和未使用抗抑郁药患者基于日记的每日平均疼痛评分（数字评分量表：0至10）每周均值的改善情况，包括对三因素交互作用（抗抑郁药亚组×治疗×周数）的检验，以评估治疗组在12周内的差异在抗抑郁药使用亚组之间是否不同。
三因素交互作用显著（P = 0.035），表明各亚组治疗组随时间的疼痛减轻差异不同。在未使用抗抑郁药的患者中，接受度洛西汀治疗的患者在第4周及直至12周终点的连续各周疼痛减轻程度均显著大于普瑞巴林（度洛西汀为-2.8，普瑞巴林为-2.1；P = 0.031）；接受度洛西汀加加巴喷丁治疗的患者在第2、3、5和7至9周疼痛减轻程度大于普瑞巴林（P≤0.05），但在终点时无差异（-2.4；P = 0.222）。在同时使用抗抑郁药的患者中，未发现治疗组间差异。
在未同时使用抗抑郁药且加巴喷丁治疗效果不佳的DPNP患者中，换用度洛西汀而非普瑞巴林可能能更好地减轻疼痛。相反，在同时使用抗抑郁药且对加巴喷丁无反应的患者中，换用度洛西汀或普瑞巴林可能能提供相似的疼痛减轻效果。
