Lieberman Jeffrey A, Papadakis Kelly, Csernansky John, Litman Robert, Volavka Jan, Jia Xinwei Daniel, Gage Allyson
Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Neuropsychopharmacology. 2009 Apr;34(5):1322-9. doi: 10.1038/npp.2008.200. Epub 2008 Nov 12.
Memantine, an uncompetitive antagonist of glutamate receptors of the N-methyl-D-aspartate type is approved for the treatment of moderate to severe Alzheimer's disease. A growing body of evidence supports a link between the glutamatergic neurotransmission and schizophrenia. The purpose of this study (MEM-MD-29) was to examine the efficacy and safety of memantine as an adjunctive treatment to atypical antipsychotics in patients with persistent residual psychopathology of schizophrenia. In this double-blind, placebo-controlled study, participants were assigned to receive 20 mg/day memantine (n=70) or placebo (n=68), in addition to continuing treatment with atypical antipsychotics, for 8 weeks. The primary efficacy measure was the total score on the Positive and Negative Symptom Scale (PANSS). Secondary measures were positive and negative PANSS scores, PANSS responders, Calgary Depression Scale for Schizophrenia (CDSS), Clinical Global Impression of Severity (CGI-S), Clinical Global Impression of Improvement (CGI-I), and Brief Assessment of Cognition in Schizophrenia (BACS). Missing data were imputed using the last observation carried forward (LOCF) approach. Safety was assessed by means of physical examination, clinical laboratory evaluation, recording of adverse events (AEs), and measures of extrapyramidal symptoms. At end point, total PANSS scores did not differ between the memantine and the placebo group (p=0.570, LOCF). A similar outcome was observed for all secondary measures. The frequency of serious AEs in the memantine vs placebo group was 8.7 vs 6.0%; treatment discontinuations because of AEs occurred in 11.6 and 3.0% of patients in these groups, respectively. Memantine showed no efficacy as an adjunctive therapy in schizophrenia patients with residual psychopathology and was associated with a higher incidence of AEs than placebo.
美金刚是一种N-甲基-D-天冬氨酸型谷氨酸受体的非竞争性拮抗剂，已被批准用于治疗中度至重度阿尔茨海默病。越来越多的证据支持谷氨酸能神经传递与精神分裂症之间存在联系。本研究（MEM-MD-29）的目的是检验美金刚作为非典型抗精神病药物辅助治疗对患有持续性精神分裂症残留精神病理学症状患者的疗效和安全性。在这项双盲、安慰剂对照研究中，参与者除了继续接受非典型抗精神病药物治疗外，被分配接受20毫克/天的美金刚（n = 70）或安慰剂（n = 68），为期8周。主要疗效指标是阳性和阴性症状量表（PANSS）的总分。次要指标包括PANSS阳性和阴性得分、PANSS反应者、精神分裂症卡尔加里抑郁量表（CDSS）、临床总体严重程度印象（CGI-S）、临床总体改善印象（CGI-I）以及精神分裂症认知简要评估（BACS）。缺失数据采用末次观察结转（LOCF）方法进行估算。通过体格检查、临床实验室评估、不良事件（AE）记录以及锥体外系症状测量来评估安全性。在研究终点，美金刚组和安慰剂组的PANSS总分没有差异（p = 0.570，LOCF）。所有次要指标均观察到类似结果。美金刚组与安慰剂组严重AE的发生率分别为8.7%和6.0%；因AE导致的治疗中断分别发生在这些组11.6%和3.0%的患者中。美金刚作为辅助治疗对有残留精神病理学症状的精神分裂症患者没有疗效，并且与比安慰剂更高的AE发生率相关。
