Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation
Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation
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DOI：
10.1177/0004867416631828
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发表时间：
2017-01-01
影响因子：
4.6
通讯作者：
Fava, Maurizio
中科院分区：
文献类型：
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作者：
Cusin, Cristina;Ionescu, Dawn Flosnik;Fava, Maurizio
目的：初步证据支持亚麻醉氯胺酮作为实验性抗抑郁药的安全性和有效性，尽管其效果通常不会持续超过一周。缺乏研究已经检查了氯胺酮剂量递增的持续影响，作为对难治性抑郁症门诊患者的增强。因此，本研究的目的有两个：（1）评估两步重复剂量氯胺酮增强的安全性和抗抑郁疗效，以及（2）评估氯胺酮的抗抑郁疗效在末次输注后3个月内作为持续抗抑郁药物治疗的增强持续时间。14名难治性抑郁症患者有资格接受6次开放标签静脉注射氯胺酮，为期3周。对于前三次输注，氯胺酮以0.5 mg/kg的剂量在45分钟内给药;对于随后的三次输注，剂量在45分钟内增加至0.75 mg/kg。主要结局指标为反应（根据汉密尔顿抑郁评定量表-28项测量）。结果：完成三次氯胺酮输注后，7.1%（1/14）有反应;完成所有六次氯胺酮输注后，41.7%（5/12）有反应，16.7%（2/12）缓解。末次输注结束时的意向治疗应答率和缓解率分别为35.7%（5/14）和14.3%（2/14）。结论：反复递增剂量静脉注射氯胺酮强化治疗急性脑梗死是可行的，有效的，耐受性良好。与合并用药的相互作用和治疗抵抗水平升高是无应答的可能因素。
Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine's antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3months after the final infusion.Methods: Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3weeks. For the first three infusions, ketamine was administered at a dose of 0.5mg/kg over 45minutes; the dose was increased to 0.75mg/kg over 45minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale-28 items).Results: After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2weeks after the final infusion.Conclusion: Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response.