Department of Psychiatry, University Neuropsychiatric Institute, University of Utah, Salt Lake City, UT.
Department of Anesthesiology, University of Utah, Salt Lake City, UT.
Int J Neuropsychopharmacol. 2018 Dec 1;21(12):1079-1089. doi: 10.1093/ijnp/pyy085.
We hypothesized that propofol, a unique general anesthetic that engages N-methyl-D-aspartate and gamma-aminobutyric acid receptors, has antidepressant properties. This open-label trial was designed to collect preliminary data regarding the feasibility, tolerability, and efficacy of deep propofol anesthesia for treatment-resistant depression.
Ten participants with moderate-to-severe medication-resistant depression (age 18-45 years and otherwise healthy) each received a series of 10 propofol infusions. Propofol was dosed to strongly suppress electroencephalographic activity for 15 minutes. The primary depression outcome was the 24-item Hamilton Depression Rating Scale. Self-rated depression scores were compared with a group of 20 patients who received electroconvulsive therapy.
Propofol treatments were well tolerated by all subjects. No serious adverse events occurred. Montreal Cognitive Assessment scores remained stable. Hamilton scores decreased by a mean of 20 points (range 0-45 points), corresponding to a mean 58% improvement from baseline (range 0-100%). Six of the 10 subjects met the criteria for response (>50% improvement). Self-rated depression improved similarly in the propofol group and electroconvulsive therapy group. Five of the 6 propofol responders remained well for at least 3 months. In posthoc analyses, electroencephalographic measures predicted clinical response to propofol.
These findings demonstrate that high-dose propofol treatment is feasible and well tolerated by individuals with treatment-resistant depression who are otherwise healthy. Propofol may trigger rapid, durable antidepressant effects similar to electroconvulsive therapy but with fewer side effects. Controlled studies are warranted to further evaluate propofol's antidepressant efficacy and mechanisms of action. ClinicalTrials.gov: NCT02935647.
我们假设丙泊酚是一种独特的全身麻醉剂，能与 N-甲基-D-天冬氨酸和γ-氨基丁酸受体结合，具有抗抑郁作用。这项开放标签试验旨在收集关于深度丙泊酚麻醉治疗难治性抑郁症的可行性、耐受性和疗效的初步数据。
10 名年龄在 18-45 岁之间、有中度至重度药物难治性抑郁症且无其他健康问题的参与者，每人接受了一系列 10 次丙泊酚输注。丙泊酚的剂量足以强烈抑制脑电图活动 15 分钟。主要的抑郁结局是 24 项汉密尔顿抑郁量表。自评抑郁评分与 20 名接受电抽搐治疗的患者进行了比较。
所有受试者均能很好地耐受丙泊酚治疗。没有发生严重不良事件。蒙特利尔认知评估量表的评分保持稳定。汉密尔顿评分平均下降 20 分（0-45 分），自基线平均改善 58%（0-100%）。10 名受试者中有 6 名达到了反应标准（>50%改善）。丙泊酚组和电抽搐治疗组的自评抑郁均有相似改善。6 名丙泊酚应答者中有 5 名至少在 3 个月内保持良好。在事后分析中，脑电图测量预测了丙泊酚的临床反应。
这些发现表明，对于其他方面健康的药物难治性抑郁症患者，高剂量丙泊酚治疗是可行的，且耐受性良好。丙泊酚可能引发与电抽搐治疗相似但副作用更少的快速、持久的抗抑郁作用。需要进行对照研究，以进一步评估丙泊酚的抗抑郁疗效及其作用机制。ClinicalTrials.gov：NCT02935647。
