Evaluation of opioid modulation in major depressive disorder.
Evaluation of opioid modulation in major depressive disorder.
复制标题
DOI：
10.1038/npp.2014.330
复制
发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然阿片类药物具有已知的抗抑郁活性，但其在重度抑郁症（MDD）中的使用受到滥用和成瘾风险的极大限制。我们的目的是确定通过μ-阿片类部分激动剂丁丙诺啡（BUP）和有效的μ-阿片类拮抗剂沙米德芬（SAM）的组合实现的阿片调节是否会表现出抗抑郁活性而无成瘾潜力。一项安慰剂对照交叉研究评估了在阿片类药物使用过的成人中SAM剂量递增与BUP联合给药后的阿片类药物药效学特征。随后在MDD和对标准抗抑郁药治疗反应不足的受试者中进行了一项为期1周的安慰剂对照平行组研究。第二项研究评价了初始研究中与阿片样物质反应的部分和最大阻滞相关的BUP/SAM比率的安全性和有效性。瞳孔测量、视觉模拟量表评估和自我报告的问卷调查表明，在固定剂量的BUP中加入越来越多的SAM，导致阿片类药物使用者的客观和主观阿片类药物效应（包括欣快感和药物喜好）呈剂量依赖性降低。在MDD受试者中治疗7天后，BUP和SAM的1：1比例（与阿片类药物作用的最大拮抗作用相关的比例）显示，与安慰剂相比，HAM-D17总评分（p=0.032）出现统计学显著性改善，蒙哥马利-韦斯伯格抑郁评定量表（MADRS）总评分（p=0.054）几乎出现显著性改善。总体而言，BUP/SAM治疗耐受性良好。BUP和SAM的组合在MDD受试者中显示出抗抑郁活性。平衡的激动剂-拮抗剂阿片调节代表了治疗MDD和其他精神疾病的一种新的和潜在的临床重要方法。
Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ-opioid partial agonist, buprenorphine (BUP), and a potent μ-opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent 1-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments, and self-reported questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist–antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.
登录
查看更多内容
影响因子：
15.9
作者：
Lutz PE;Kieffer BL
通讯作者：
Kieffer BL
影响因子：
13.5
作者：
Carlezon WA Jr;Béguin C;Knoll AT;Cohen BM
通讯作者：
Cohen BM
DOI：
10.4088/jcp.13m08725
发表时间：
2014-08
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
Karp JF;Butters MA;Begley AE;Miller MD;Lenze EJ;Blumberger DM;Mulsant BH;Reynolds CF 3rd
通讯作者：
Reynolds CF 3rd
影响因子：
6.7
作者：
McCann, D. J.
通讯作者：
McCann, D. J.
DOI：
10.1111/j.1749-6632.1982.tb39483.x
发表时间：
1982-01-01
影响因子：
5.2
作者：
EMRICH, HM;VOGT, P;HERZ, A
通讯作者：
HERZ, A