BACKGROUND Demand for treatments for severe opioid use disorder is increasing worldwide. The current pharmacotherapy is mainly focused on opioid and adrenergic receptors. The N-methyl-d-aspartate receptor (NMDAR) is among other receptors that can also be targeted to treat the disease. Findings from randomized controlled trials (RTCs) on NMDAR antagonists to treat severe opioid use disorder amply varied. This study aimed to evaluate the clinical benefits and assess the potential risks for adverse events or side effects of NMDAR antagonists that were investigated for the treatment of severe opioid use disorder. METHODS Articles were searched in PubMed, Scopus, Google Scholar, Proquest. Cochrane Review Database, Medline Ovid, and EMBASE from their inception to March 2019. RTCs on NMDAR antagonists for the treatment of severe opioid use disorder were independently screened and assessed by two authors. The results were synthesized qualitatively. RESULTS Nineteen RTCs of 1459 participants met the inclusion criteria. There is moderate evidence suggesting that ketamine, memantine, amantadine, and dextromethorphan may be able to manage opioid withdrawal symptoms. There is little evidence suggesting that memantine may be able to reduce methadone maintenance dose in participants on methadone, reduce opioid use, and reduce craving. Dropout is noticeable among dextromethorphan's participants. Safety concerns are more likely associated with dextromethorphan and ketamine. CONCLUSIONS NMDAR antagonists have the potentiality to treat severe opioid use disorder. There is insufficient evidence to recommend them for the treatment of severe opioid use disorder due to several limitations inherent to the RCTs reviewed. Further exploration is needed.

中文翻译：

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N-甲基-d-天冬氨酸受体拮抗剂治疗严重阿片类药物使用障碍的临床获益和风险：系统评价。

背景技术在世界范围内，对治疗严重阿片类药物使用障碍的需求正在增加。当前的药物疗法主要集中在阿片样物质和肾上腺素能受体上。N-甲基-d-天门冬氨酸受体（NMDAR）是也可以靶向治疗该疾病的其他受体之一。NMDAR拮抗剂治疗严重阿片类药物使用障碍的随机对照试验（RTC）发现差异很大。这项研究旨在评估临床获益，并评估被研究用于治疗严重阿片类药物使用障碍的NMDAR拮抗剂的不良事件或副作用的潜在风险。方法在PubMed，Scopus，Google Scholar，Proquest中搜索文章。Cochrane评价数据库，Medline Ovid和EMBASE从成立到2019年3月。由两位作者独立筛选和评估了用于治疗严重阿片类药物使用障碍的NMDAR拮抗剂的RTC。结果定性地合成。结果1459名参与者中的19个RTC符合纳入标准。有中等证据表明，氯胺酮，美金刚，金刚烷胺和右美沙芬可能能够控制阿片类药物戒断症状。几乎没有证据表明美金刚可以降低美沙酮参与者的美沙酮维持剂量，减少阿片类药物的使用和减少渴望。右美沙芬的参与者中明显有辍学现象。安全隐患更可能与右美沙芬和氯胺酮有关。结论NMDAR拮抗剂具有治疗严重阿片类药物使用障碍的潜力。由于所审查的RCT固有的一些局限性，因此没有足够的证据推荐它们用于治疗严重的阿片类药物使用障碍。需要进一步的探索。