Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Medical College of Wisconsin, Wausau, WI, USA.
Transl Psychiatry. 2018 Jun 15;8(1):117. doi: 10.1038/s41398-018-0162-2.
Among patients with Parkinson's disease (PD), depression is prevalent and disabling, impacting both health outcomes and quality of life. There is a critical need for alternative pharmacological methods to treat PD depression, as mainstream antidepressant drugs are largely ineffective in this population. Currently, there are no recommendations for the optimal treatment of PD neuropsychiatric symptoms. Given the dual antidepressant and anti-dyskinetic effects of ketamine and other N-methyl-D-aspartate (NMDA) antagonists for PD, this review aims to examine the current evidence of NMDA antagonists for treating neuropsychiatric symptoms, including memantine, amantadine, ketamine, dizoclopine, and d-cycloserine. A comprehensive literature search was conducted using the PubMed database. We also searched the following databases up to March 1, 2018: Ovid MEDLINE, PsycINFO, CINAHL, Google Scholar, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The following keywords were used: NMDA antagonist and Parkinson's disease. Two authors independently reviewed the articles identified from the search using specific selection criteria, focusing on studies of mood, psychiatric condition, depression, cognition, and quality of life, and the consensus was reached on the 20 studies included. There is a preliminary evidence that NMDA antagonists may modulate psychiatric symptoms in PD. However, current evidence of psychiatric symptom-modifying effects is inconclusive and requires that further trials be conducted in PD. The repurposing of old NMDA antagonists, such as ketamine for depression and newer therapies, such as rapastinel, suggests that there is an emerging place for modulating the glutamatergic system for treating non-motor symptoms in PD.
在帕金森病（PD）患者中，抑郁很常见且具有致残性，影响健康结局和生活质量。因此，迫切需要替代的药理学方法来治疗 PD 抑郁，因为主流的抗抑郁药在这一人群中效果不大。目前，对于 PD 神经精神症状的最佳治疗方法尚无建议。鉴于氯胺酮和其他 N-甲基-D-天冬氨酸（NMDA）拮抗剂对 PD 具有双重抗抑郁和抗运动障碍作用，本综述旨在检查 NMDA 拮抗剂治疗神经精神症状的现有证据，包括美金刚、金刚烷胺、氯胺酮、地佐辛和 D-环丝氨酸。使用 PubMed 数据库进行了全面的文献检索。我们还在截至 2018 年 3 月 1 日之前搜索了以下数据库：Ovid MEDLINE、PsycINFO、CINAHL、Google Scholar、Cochrane 对照试验中心注册库和 Cochrane 系统评价数据库。使用了以下关键字：NMDA 拮抗剂和帕金森病。两名作者独立使用特定的选择标准审查了从搜索中确定的文章，重点关注情绪、精神病状况、抑郁、认知和生活质量的研究，并就包括的 20 项研究达成共识。有初步证据表明 NMDA 拮抗剂可能调节 PD 中的精神症状。然而，目前关于改变精神病症状的证据尚无定论，需要在 PD 中进行进一步的试验。旧的 NMDA 拮抗剂的重新利用，如氯胺酮治疗抑郁，以及新的疗法，如拉帕司汀，表明调节谷氨酸能系统治疗 PD 中非运动症状有了新的可能。
