Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial
Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial
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DOI：
10.1176/appi.ajp.2015.15070921
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发表时间：
2016-05-01
影响因子：
17.7
通讯作者：
Ehrich, Elliot
中科院分区：
文献类型：
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作者：
Fava, Maurizio;Memisoglu, Asli;Ehrich, Elliot
目的：重度抑郁症与内源性阿片系统失调有关。作者试图确定通过施用 ALKS 5461 实现的阿片类药物调节是否会对重度抑郁症患者表现出抗抑郁活性。ALKS 5461 是一种 mu-和 kappa-阿片类部分激动剂丁丙诺啡和一种 mu-阿片拮抗剂萨米多芬的组合。方法：在对一种药物反应不足的重度抑郁症成人患者中进行了一项多中心、随机、双盲、安慰剂对照、两阶段序贯平行比较设计研究。或两个疗程的抗抑郁药治疗。参与者被随机分配接受 2 mg/2 mg 丁丙诺啡/沙米多芬（2/2 剂量组）、8 mg/8 mg 丁丙诺啡/沙米多芬（8/8 剂量组）或安慰剂的辅助治疗。根据 17 项汉密尔顿抑郁量表 (HAM-D)、蒙哥马利-阿斯伯格抑郁量表 (MADRS) 和临床总体印象严重程度量表 (CGI-S) 从基线到治疗 4 周结束时的变化来衡量抗抑郁效果。 结果：与安慰剂组相比，2/2 剂量组在三项抑郁结果指标上有显着更大的改善（HAM-D： -22.8，95% CI= -5.1，-0.6；MADRS：-4.9，95% CI= -8.2，-1.6；CGI-S：-0.5，95% CI= -0.9，-0.1）。 8/8剂量组也有改善的证据，尽管没有达到统计学显着性。总体而言，丁丙诺啡/沙米多芬组合具有良好的耐受性，并且没有证据显示停药后阿片类药物戒断。结论：丁丙诺啡/沙米多芬组合是一种新颖且有前途的候选药物，用于治疗对标准抗抑郁药反应不足的重度抑郁症患者。
Objective: Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a mu- and kappa-opioid partial agonist, buprenorphine, and a mu-opioid antagonist, samidorphan, would exhibit antidepressant activity in patients with major depression.Method: A multicenter, randomized, double-blind, placebo-controlled, two-stage sequential parallel comparison design study was conducted in adults with major depression who had an inadequate response to one or two courses of antidepressant treatment. Participants were randomly assigned to receive adjunctive treatment with 2 mg/2 mg of buprenorphine/samidorphan (the 2/2 dosage group), 8 mg/8 mg of buprenorphine/samidorphan (the 8/8 dosage group), or placebo. Antidepressant effect was measured based on change from baseline to the end of 4 weeks of treatment on the 17-item Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions severity scale (CGI-S).Results: Compared with the placebo group, there were significantly greater improvements in the 2/2 dosage group across the three depression outcome measures (HAM-D: -22.8, 95% CI= -5.1,-0.6; MADRS: -4.9,95% CI= -8.2,-1.6; CGI-S: -0.5, 95% CI= -0.9,-0.1). There was also evidence of improvement in the 8/8 dosage group, although it did not achieve statistical significance. Overall, the buprenorphine/samidorphan combinations were well tolerated, and there was no evidence of opioid withdrawal on treatment discontinuation.Conclusions: The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants.