Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression
Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression
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DOI：
10.1016/j.biopsych.2009.08.038
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发表时间：
2010-01-15
影响因子：
10.6
通讯作者：
Mathew, Sanjay J.
中科院分区：
文献类型：
--
作者：
aan het Rot, Marije;Collins, Katherine A.;Mathew, Sanjay J.
背景：单次亚麻醉（静脉注射）氯胺酮可能对难治性抑郁症（TRD）患者有快速但短暂的抗抑郁作用。在这里，我们测试了重复剂量的开放标签IV氯胺酮（12天内6次输注）在10名无药物症状的TRD患者中的耐受性、安全性和有效性，这些患者之前对单次剂量显示出有意义的抗抑郁反应。方法：第1天，患者静脉滴注氯胺酮40 min。5mg /kg)，在住院环境中进行持续的生命体征监测。反复记录拟精神作用和不良事件。主要疗效测量指标为Montgomery-Asberg抑郁评定量表（MADRS）评分较基线的变化。如果患者在第2天的MADRS评分下降>= 50%，他们在门诊基础上接受5次额外的输液（第3、5、8、10和12天）。每周随访2次，持续4周或直至复发。结果：氯胺酮引起轻微阳性精神病症状。3例患者有明显但短暂的分离症状。每次氯胺酮输注期间和之后的副作用一般都很轻微。9例患者在第一次输注和第六次输注后均达到缓解标准。第六次输注后MADRS评分平均（SD）降低85%（12%）。服用氯胺酮后，9名患者中有8名在第六次输注后平均19天（6天-45天）复发。一名患者保持无抗抑郁药，抑郁症状最小，持续30个月。结论：这些初步研究结果提示氯胺酮静脉注射用于急性TRD治疗的可行性。
Background: A single subanesthetic (intravenous) IV dose of ketamine might have rapid but transient antidepressant effects in patients with treatment-resistant depression (TRD). Here we tested the tolerability, safety, and efficacy of repeated-dose open-label IV ketamine (six infusions over 12 days) in 10 medication-free symptomatic patients with TRD who had previously shown a meaningful antidepressant response to a single dose.Methods: On day 1, patients received a 40-min IV infusion of ketamine (.5 mg/kg) in an inpatient setting with continuous vital-sign monitoring. Psychotomimetic effects and adverse events were recorded repeatedly. The primary efficacy measure was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) score. If patients showed a >= 50% reduction in MADRS scores on day 2, they received five additional infusions on an outpatient basis (days 3, 5, 8, 10, and 12). Follow-up visits were conducted twice-weekly for >= 4 weeks or until relapse.Results: Ketamine elicited minimal positive psychotic symptoms. Three patients experienced significant but transient dissociative symptoms. Side effects during and after each ketamine infusion were generally mild. The response criterion was met by nine patients after the first infusion as well as after the sixth infusion. The mean (SD) reduction in MADRS scores after the sixth infusion was 85% (12%). Postketamine, eight of nine patients relapsed, on average, 19 days after the sixth infusion (range 6 days-45 days). One patient remained antidepressant-free with minimal depressive symptoms for > 3 months.Conclusions: These pilot findings suggest feasibility of repeated-dose IV ketamine for the acute treatment of TRD.