Ketamine for Depression, 5: Potential Pharmacokinetic and Pharmacodynamic Drug Interactions
Ketamine for Depression, 5: Potential Pharmacokinetic and Pharmacodynamic Drug Interactions
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DOI：
10.4088/jcp.17f11802
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发表时间：
2017-07-01
影响因子：
5.3
通讯作者：
Andrade, Chittaranjan
中科院分区：
文献类型：
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作者：
Andrade, Chittaranjan
以亚麻醉剂量给药的氯胺酮正在被公认为是一种治疗严重甚至治疗难治性抑郁症的非标签疗法。本文探讨了与使用氯胺酮治疗抑郁症相关的潜在的药代动力学和药效学药物相互作用。少数证据表明，氯胺酮不会引起临床上显著的药物相互作用，除非这些相互作用是通过其临床作用可以预测的。一小部分文献表明，诱导细胞色素P450(CYP)2B6和CYP3A4的药物将减少氯胺酮的暴露，而抑制这些酶的药物将增加氯胺酮的暴露。CYP2B6基因常见的遗传多态也可能与氯胺酮暴露的变异有关。然而，这种暴露变化的临床意义还没有得到充分的研究。极少数报告和研究表明，同时服用苯二氮卓类药物可能会削弱氯胺酮的抗抑郁作用。同样，一小部分文献表明，抑制谷氨酸能信号转导的药物(如拉莫三嗪)可能会减少氯胺酮的不良反应；然而，这些药物是否也降低了抗抑郁作用尚不清楚。来自临床试验的数据表明，大多数传统的抗抑郁药可能可以与氯胺酮联合使用，而不会影响疗效或增加不良反应负担。
Ketamine, administered in subanesthetic doses, is gaining recognition as an off-label treatment for severe and even treatment-refractory depression. This article explores potential pharmacokinetic and pharmacodynamic drug interactions of relevance to the use of ketamine in depression. Sparse evidence suggests that ketamine will not induce clinically significant drug interactions except to the extent that these are predictable by its clinical actions. A small body of literature indicates that drugs that induce cytochrome P450 (CYP) 2B6 and CYP3A4 will reduce exposure to ketamine and that drugs that inhibit these enzymes will increase exposure to ketamine. Common genetic polymorphisms of the CYP2B6 gene may also be associated with variations in the exposure to ketamine. However, the clinical implications of such variations in exposure have not been sufficiently studied. A very small number of reports and studies suggest that concurrent benzodiazepine medication may diminish the antidepressant benefits of ketamine. Likewise, a small body of literature suggests that drugs (such as lamotrigine) that inhibit glutamatergic signaling may reduce the adverse effects of ketamine; however, it is unknown whether these drugs also diminish the antidepressant effect. Data from clinical trials indicate that most conventional antidepressants can probably be combined with ketamine without compromising efficacy or increasing the adverse effect burden.