From the Mood Disorders Research Unit, The Royal's Institute of Mental Health Research, Ottawa (Phillips, Norris, Talbot, Birmingham, Hatchard, Ortiz, Owoeye, Batten, Blier); the Department of Psychiatry, University of Ottawa (Phillips, Norris, Talbot, Owoeye, Blier); and the Department of Cellular and Molecular Medicine, University of Ottawa (Blier).
Am J Psychiatry. 2019 May 1;176(5):401-409. doi: 10.1176/appi.ajp.2018.18070834. Epub 2019 Mar 29.
Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions.
Forty-one participants with treatment-resistant depression completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam (an active placebo control). After relapse of depressive symptoms, participants received a course of six open-label ketamine infusions administered thrice weekly over 2 weeks. Responders, classified as those participants who had a ≥50% decrease in their scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), received four additional infusions administered once weekly (maintenance phase).
Compared with midazolam, a single ketamine infusion elicited a significantly greater reduction in depressive symptoms at the primary efficacy endpoint (24 hours postinfusion). Linear mixed models revealed cumulative antidepressant effects with repeated infusions and doubling of the antidepressant response rate. Fifty-nine percent of participants met response criteria after repeated infusions, with a median of three infusions required before achieving response. Participants had no further change in MADRS scores during weekly maintenance infusions.
Repeated ketamine infusions have cumulative and sustained antidepressant effects. Reductions in depressive symptoms were maintained among responders through once-weekly infusions. These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression. Future studies should further expand on optimizing administration to better translate the use of ketamine into clinical settings.
亚麻醉剂量氯胺酮已被证明对治疗抵抗性抑郁症患者具有快速但短暂的抗抑郁作用，这种作用可通过重复给药而延长。本研究旨在评估单次氯胺酮输注、多次重复氯胺酮输注以及通过维持输注延长反应时间的抗抑郁效果。
41 名治疗抵抗性抑郁症患者完成了一项单中心、随机、双盲交叉对照研究，比较了单次氯胺酮和咪达唑仑（一种活性安慰剂对照）输注。在抑郁症状复发后，患者接受了为期 2 周、每周 3 次的 6 次开放标签氯胺酮输注疗程。应答者（定义为 Montgomery-Åsberg 抑郁评定量表（MADRS）评分下降≥50%的患者）接受了 4 次每周一次的额外输注（维持阶段）。
与咪达唑仑相比，单次氯胺酮输注在主要疗效终点（输注后 24 小时）时能显著减轻抑郁症状。线性混合模型显示，重复输注具有累积抗抑郁作用，并使抗抑郁反应率增加一倍。59%的患者在重复输注后符合应答标准，需要 3 次输注才能达到应答。在每周维持输注期间，参与者的 MADRS 评分没有进一步变化。
重复氯胺酮输注具有累积和持续的抗抑郁作用。在应答者中，抑郁症状的减轻通过每周一次的输注得以维持。这些发现为治疗抵抗性抑郁症患者氯胺酮的有效给药策略提供了新的数据。未来的研究应进一步优化给药以更好地将氯胺酮的使用转化为临床环境。
