Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Psychiatric Research Center, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.
J Psychopharmacol. 2021 Mar;35(3):236-252. doi: 10.1177/0269881120965937. Epub 2021 Jan 6.
Dysfunction of the -methyl--aspartate glutamate receptor is involved in the putative pathology of schizophrenia. There is growing interest in the potential of -methyl--aspartate receptor modulators to improve the symptoms of schizophrenia, but the evidence for the use of glutamatergic agents for augmenting schizophrenia remains inconclusive.
We conducted a meta-analysis to test the efficacy and safety of -methyl--aspartate receptor modulator supplements in patients with schizophrenia.
Following a systemic search in MEDLINE, Embase, Cochrane and Scopus, 40 double-blinded, randomised, placebo-controlled trials involving 4937 patients with schizophrenia were included in this meta-analysis. The change in the severity of symptoms among patients with schizophrenia was defined as the primary outcome, whereas the safety profiles of the intervention, including the discontinuation rate and adverse events, were defined as secondary outcomes.
When added to antipsychotic treatments, -methyl--aspartate receptor modulators improved multiple schizophrenia symptoms, particularly negative symptoms, and had satisfactory side effects and safety profile. Among the seven glutamatergic agents analysed, glycine, D-serine and sarcosine had better treatment profiles than other agents, and NMDA receptor co-agonists, as a group, provided a reduction in schizophrenia symptoms compared to antipsychotic treatments without supplementation. Augmentation with -methyl--aspartate receptor modulators was only effective among patients treated with antipsychotics other than clozapine.
The results indicate that -methyl--aspartate receptor modulators, particularly with glycine, D-serine and sarcosine, are more beneficial than the placebo in treating schizophrenia, and the effects extended to both positive and negative symptoms, when augmented with antipsychotics other than clozapine.
-甲基-D-天冬氨酸谷氨酸受体功能障碍与精神分裂症的假定病理有关。人们对 -甲基-D-天冬氨酸受体调节剂改善精神分裂症症状的潜力越来越感兴趣，但用于增强精神分裂症的谷氨酸能药物的证据仍不确定。
我们进行了一项荟萃分析，以测试 -甲基-D-天冬氨酸受体调节剂补充剂在精神分裂症患者中的疗效和安全性。
在 MEDLINE、Embase、Cochrane 和 Scopus 进行系统搜索后，纳入了 40 项涉及 4937 名精神分裂症患者的双盲、随机、安慰剂对照试验，进行了这项荟萃分析。精神分裂症患者症状严重程度的变化定义为主要结局，而干预措施的安全性概况，包括停药率和不良事件，定义为次要结局。
当与抗精神病药物治疗联合使用时，-甲基-D-天冬氨酸受体调节剂改善了多种精神分裂症症状，特别是阴性症状，且具有良好的副作用和安全性。在分析的七种谷氨酸能药物中，甘氨酸、D-丝氨酸和肌氨酸的治疗效果优于其他药物，作为一个整体，NMDA 受体共激动剂与不补充 NMDA 受体共激动剂相比，与抗精神病药物治疗相比，能降低精神分裂症症状。-甲基-D-天冬氨酸受体调节剂的增强作用仅在接受氯氮平以外的抗精神病药物治疗的患者中有效。
结果表明，-甲基-D-天冬氨酸受体调节剂，特别是甘氨酸、D-丝氨酸和肌氨酸，与安慰剂相比，在治疗精神分裂症方面更有益，且在与氯氮平以外的抗精神病药物联合使用时，对阳性和阴性症状都有疗效。
