Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism.
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阿片受体拮抗作用氯胺酮抗抑郁作用的衰减。
DOI：
10.1176/appi.ajp.2018.18020138
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发表时间：
2018-12-01
期刊：
影响因子：
--
通讯作者：
Schatzberg AF
中科院分区：
文献类型：
--
作者：
Williams NR;Heifets BD;Blasey C;Sudheimer K;Pannu J;Pankow H;Hawkins J;Birnbaum J;Lyons DM;Rodriguez CI;Schatzberg AF
除了N-甲基D-天冬氨酸受体拮抗作用外，氯胺酮还产生阿片系统激活作用。本研究的目的是确定静脉内氯胺酮给药前阿片受体拮抗作用是否减弱其急性抗抑郁和/或解离作用。在一项对30名患有难治性抑郁症的成年人进行的拟议双盲交叉研究中，我们在研究了14名参与者后进行了计划的中期分析，其中12名参与者以随机顺序完成了两种条件：50 mg纳洛酮先于0.5 mg/kg氯胺酮或安慰剂先于0.5 mg/kg氯胺酮。在中期分析中，12例难治性抑郁症成人患者中有7例在氯胺酮+安慰剂条件下符合应答者标准，定义为第1天17项汉密尔顿抑郁量表评分降低≥50%。在输注后第1天和第3天，氯胺酮+纳洛酮条件下受试者的汉密尔顿抑郁评定量表6和17项评分的降低显著低于氯胺酮+安慰剂条件下的评分。对所有完成安慰剂和纳洛酮条件的参与者进行的次要分析显示了相似的结果，无论对氯胺酮的反应是否稳健。不同条件下氯胺酮诱导的解离无差异。由于纳洛酮显著阻断了抗抑郁药，但不能阻断氯胺酮的解离作用，因此试验在中期分析时停止。氯胺酮的急性抗抑郁作用似乎需要阿片系统激活。氯胺酮在人体中的解离作用不是由阿片系统介导的，在没有阿片作用的情况下，这些作用似乎也不足以在患有难治性抑郁症的成人中产生氯胺酮的急性抗抑郁作用。
In addition to N-methyl D-aspartate receptor antagonism, ketamine produces opioid system activation. The objective of the study was to determine if opioid receptor antagonism prior to administration of intravenous ketamine attenuates its acute antidepressant and/or dissociative effects. In a proposed double-blind, cross-over study of 30 adults with treatment-resistant depression, we performed a planned interim analysis after studying 14 participants, 12 of whom completed both conditions in randomized order: 50mg naltrexone preceding 0.5mg/kg ketamine or placebo preceding 0.5mg/kg ketamine. In the interim analysis, 7 of 12 adults with treatment-resistant depression met responder criteria during the ketamine + placebo condition, defined as a ≥50% reduction on the 17-item Hamilton Depression Scale score at Day 1. The subjects’ reductions in Hamilton Depression Rating Scale 6 and 17-item ratings in the ketamine + naloxone condition were significantly lower than the ratings in the ketamine + placebo condition at post-infusion Days 1 and 3. Secondary analysis of all participants completing both placebo and naloxone conditions, regardless of the robustness of response to ketamine, showed similar results. There were no differences in ketamine-induced dissociation between conditions. Because naltrexone dramatically blocked the antidepressant but not the dissociative effects of ketamine, the trial was halted at the interim analysis. Ketamine’s acute antidepressant effect appears to require opioid system activation. Dissociative effects of ketamine in humans are not mediated by the opioid system, nor do they appear sufficient without the opioid effect to produce the acute antidepressant effects of ketamine in adults with treatment-resistant depression.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
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13.5
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25.8
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通讯作者：
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影响因子：
11
作者：
Cavalleri, L.;Pich, E. Merlo;Collo, G.
通讯作者：
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