Ketamine for Treatment-Resistant Mood Disorders.
Ketamine for Treatment-Resistant Mood Disorders.
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DOI：
10.1176/appi.focus.20180030
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Zarate, Carlos A Jr
中科院分区：
文献类型：
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作者：
Park, Lawrence T;Falodun, Tolulope B;Zarate, Carlos A Jr
强有力的证据支持单次静脉注射氯胺酮对难治性重性抑郁症（MDD）和双相抑郁症的快速（尽管是暂时的）抗抑郁作用。虽然氯胺酮对脑神经递质有不同的影响，但目前的理论认为N-甲基-d-天冬氨酸拮抗剂在突触前中间神经元中介导其抗抑郁作用。当由经过培训的专业人员给药时，静脉注射氯胺酮治疗难治性抑郁症（TRD）通常是安全的，耐受性良好。反复静脉输注氯胺酮作为TRD的标签外治疗越来越多地用于临床，尽管其安全性和有效性尚未得到很好的表征。鼻内给药艾司氯胺酮-外消旋氯胺酮的（S）-对映体-最近完成的III期多中心试验;预计将向美国食品药品监督管理局申请其用于TRD。关于氯胺酮治疗TRD的长期副作用知之甚少。人们对它的解离性副作用、滥用风险以及在较高剂量和重复使用时的潜在兴奋性毒性神经元损伤表示担忧。需要制定治疗指南，以规范氯胺酮在精神疾病中的使用。氯胺酮的研究正在改变我们对情绪障碍病理生理学的理解，并为TRD开发新的快速干预措施铺平道路。
Strong evidence supports the rapid, although temporary, antidepressant effects of a single intravenous ketamine infusion for treatment-resistant major depressive disorder (MDD) and bipolar depression. Although ketamine has diverse effects on brain neurotransmitters, current theories have implicated N-methyl-d-aspartate antagonist effects at the presynaptic interneuron in mediating its antidepressant effects. Intravenous ketamine administration for treatment-resistant depression (TRD) is generally safe and well tolerated when administered by trained professionals. Repeated intravenous ketamine infusions as an off-label treatment for TRD are increasingly available for clinical use, although their safety and effectiveness are not well characterized. Intranasal administration of esketamine-the (S)-enantiomer of racemic ketamine-recently completed phase 3 multicenter trials; a Food and Drug Administration application for its use in TRD is expected. Relatively little is known about the longer term side effects of ketamine for TRD. Concerns have been raised about its dissociative side effects, risk of abuse, and potential excitotoxic neuronal injury at higher doses and with repeated use. Treatment guidelines are needed to standardize ketamine use in psychiatric disorders. Ketamine research is transforming our understanding of the pathophysiology of mood disorders and leading the way toward developing new, rapid-acting interventions for TRD.