One Bowdoin Sq, 9th Floor, Boston, MA 02114.
Massachusetts General Hospital Clinical Trials Network and Institute, Boston, Massachusetts, USA.
J Clin Psychiatry. 2020 Feb 4;81(2):19r12859. doi: 10.4088/JCP.19r12859.
Several controlled trials have demonstrated the rapid effects of intravenous ketamine. As a result, the use of this off-label treatment has grown exponentially in recent years. This use is expected to continue to grow after the approval by the US Food and Drug Administration of intranasal esketamine for treatment-resistant depression-a decision that firmly establishes N-methyl-d-aspartate (NMDA)-receptor antagonism as a valid antidepressant mechanism of action in the public view. The limitation, however, of intravenous ketamine administration is that much less is known about how to maintain initial treatment gains. Thus, although intravenous ketamine has proved to be a rapid-acting antidepressant, maintaining its early therapeutic gains in an efficient manner has emerged as a major unmet need in the field.
PubMed/MEDLINE was searched from inception to March 1, 2019, using the following terms: ketamine, randomized, depression, and placebo. There were no language or date restrictions.
The search was limited to randomized, placebo-controlled trials to maintain initial treatment gains of intravenous ketamine for major depressive disorder. A total of 115 manuscripts were identified, and 110 were excluded because they did not describe randomized, double-blind clinical trials.
The remaining 5 articles were reviewed.
Three negative studies involving 2 oral agents (lithium and riluzole), a small negative study involving repeated ketamine infusions, and a positive yet insufficiently controlled larger study supporting infusions 2 or 3 times weekly were published.
This evidence base is insufficient to inform clinical practice. Fortunately, a wide variety of molecular targets exist for this indication. Psychotherapy and exercise may also play a beneficial role. More studies are urgently needed to establish how best to maintain rapid symptom improvement seen with ketamine infusions.
多项对照试验已经证实静脉注射氯胺酮具有快速疗效。因此，近年来，这种超适应证治疗的应用呈指数级增长。美国食品和药物管理局批准鼻腔内给予依他佐辛治疗难治性抑郁症的决定使 N-甲基-D-天冬氨酸（NMDA）受体拮抗作用成为公众公认的一种有效的抗抑郁作用机制，这一决定预计将进一步推动其应用。然而，静脉注射氯胺酮的局限性在于，人们对如何维持初始治疗效果知之甚少。因此，虽然静脉注射氯胺酮已被证明是一种快速起效的抗抑郁药，但如何以有效的方式维持其早期治疗效果已成为该领域的一个主要未满足的需求。
从建库到 2019 年 3 月 1 日，使用以下术语在 PubMed/MEDLINE 上进行检索：氯胺酮、随机、抑郁、安慰剂。无语言或日期限制。
该检索仅限于随机、安慰剂对照试验，以维持静脉注射氯胺酮治疗重性抑郁障碍的初始治疗效果。共确定了 115 篇手稿，其中 110 篇因未描述随机、双盲临床试验而被排除。
对其余 5 篇文章进行了综述。
共发表了 3 项阴性研究，涉及 2 种口服药物（锂盐和利鲁唑）、1 项涉及重复氯胺酮输注的小型阴性研究和 1 项阳性但控制不足的较大研究，该研究支持每周输注 2 或 3 次。
这一证据基础不足以为临床实践提供信息。幸运的是，针对这一适应证存在多种分子靶标。心理治疗和运动也可能发挥有益作用。迫切需要开展更多的研究，以确定如何最好地维持氯胺酮输注带来的快速症状改善。
