Cusin Cristina, Ionescu Dawn Flosnik, Pavone Kara Jean, Akeju Oluwaseun, Cassano Paolo, Taylor Norman, Eikermann Matthias, Durham Kelley, Swee Michaela Ballentyne, Chang Trina, Dording Christina, Soskin David, Kelley John, Mischoulon David, Brown Emery Neal, Fava Maurizio
1 Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
2 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Aust N Z J Psychiatry. 2017 Jan;51(1):55-64. doi: 10.1177/0004867416631828.
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 3 months after the final infusion.
Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3 weeks. For the first three infusions, ketamine was administered at a dose of 0.5 mg/kg over 45 minutes; the dose was increased to 0.75 mg/kg over 45 minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale-28 items).
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 2 weeks after the final infusion.
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.
初步证据支持亚麻醉剂量的氯胺酮作为一种实验性抗抑郁药的安全性和有效性，尽管其效果通常在一周后难以持续。目前缺乏关于递增氯胺酮剂量作为增效剂对难治性抑郁症门诊患者的持续影响的研究。因此，本研究的目的有两个：（1）评估两步重复剂量氯胺酮增效治疗的安全性和抗抑郁疗效；（2）评估在最后一次输注后3个月内，氯胺酮作为增效剂对正在进行的抗抑郁药物治疗的抗抑郁疗效持续时间。
14例难治性抑郁症患者符合条件，在3周内接受6次开放标签的静脉注射氯胺酮增效治疗。前三次输注时，氯胺酮以0.5mg/kg的剂量在45分钟内给药；随后三次输注时，剂量增加至0.75mg/kg，输注时间为45分钟。主要结局指标为反应情况（采用28项汉密尔顿抑郁量表进行测量）。
在完成三次氯胺酮输注后，7.1%（1/14）的患者有反应；在完成所有六次氯胺酮输注后，41.7%（5/12）的完成治疗者有反应，16.7%（2/12）的患者缓解。在最后一次输注结束时，意向性治疗的反应率和缓解率分别为35.7%（5/14）和14.3%（2/14）。然而，除一名有反应者外，所有患者在最后一次输注后2周内复发。
初步发现重复递增剂量的静脉注射氯胺酮增效治疗是可行、有效且耐受性良好的。与联合用药的相互作用以及较高的治疗抵抗水平可能是无反应的因素。
