Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA.
Interventional Psychiatric Service, Yale School of Medicine, New Haven, Connecticut, USA.
Psychother Psychosom. 2021;90(5):318-327. doi: 10.1159/000517074. Epub 2021 Jun 29.
Ketamine has emerged as a rapid-acting antidepressant. While ongoing treatment can prevent relapse, concerns exist regarding long-term exposure.
We conducted a randomized trial to examine the feasibility and efficacy of cognitive behavioral therapy (CBT) following intravenous ketamine in treatment-resistant depression (TRD).
Subjects with TRD were recruited and treated with 6 intravenous infusions of ketamine over 3 weeks. Subjects who experienced a clinical response (≥50% improvement in depression severity) were then randomized to receiving CBT or treatment as usual (TAU) for an additional 14 weeks, using a sequential treatment model.
Of the 42 patients who signed consent, 28 patients achieved a response and were randomized to CBT or TAU. When measured using the Montgomery-Asberg Depression Rating Scale (primary outcome measure), the effect size at the end of the study was moderate (Cohen d = 0.65; 95% CI -0.55 to 1.82), though the group-by-time interaction effect was not significant. There was a significant group-by-time interaction as measured by the Quick Inventory of Depressive Symptomatology (F = 4.58; p = 0.033), favoring a greater sustained improvement in the CBT group. This corresponded to a moderate-to-large effect size of the Cohen d = 0.71 (95% CI -0.30 to 1.70) at the end of the study (14 weeks following the last ketamine infusion). In a subset of patients (N = 20) who underwent cognitive testing using the emotional N-back assessments before and after ketamine, ketamine responders showed improvement in the accuracy of emotional N-back (t[8] = 2.33; p < 0.05) whereas nonresponders did not (t[10] <1; p ns).
This proof-of-concept study provides preliminary data indicating that CBT may sustain the antidepressant effects of ketamine in TRD. Further study and optimization of this treatment approach in well-powered clinical trials is recommended.
氯胺酮已成为一种快速起效的抗抑郁药。虽然持续治疗可以预防复发，但人们对长期暴露于氯胺酮存在担忧。
我们进行了一项随机试验，以检查在治疗抵抗性抑郁症（TRD）中静脉注射氯胺酮后认知行为疗法（CBT）的可行性和疗效。
招募 TRD 患者，并在 3 周内接受 6 次静脉输注氯胺酮。对出现临床反应（抑郁严重程度改善≥50%）的患者进行随机分组，接受 CBT 或常规治疗（TAU），为期 14 周，采用序贯治疗模型。
在签署同意书的 42 名患者中，28 名患者达到了反应，并被随机分配到 CBT 或 TAU 组。当使用蒙哥马利-阿斯伯格抑郁评定量表（主要结局测量指标）进行测量时，研究结束时的效应大小为中度（Cohen d = 0.65；95%CI-0.55 至 1.82），尽管组间时间交互效应不显著。根据快速抑郁症状自评量表（F = 4.58；p = 0.033）的测量，存在显著的组间时间交互作用，CBT 组的持续改善更为明显。这对应于研究结束时（最后一次氯胺酮输注后 14 周）Cohen d = 0.71（95%CI-0.30 至 1.70）的中到大效应大小。在接受氯胺酮前后使用情绪 N-back 认知测试的患者亚组（N = 20）中，氯胺酮反应者的情绪 N-back 准确性有所提高（t[8] = 2.33；p <0.05），而非反应者则没有（t[10] <1；p ns）。
这项概念验证研究提供了初步数据，表明 CBT 可能维持 TRD 中氯胺酮的抗抑郁作用。建议在更有力的临床试验中进一步研究和优化这种治疗方法。
