Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India.
J Clin Psychiatry. 2017 Nov/Dec;78(9):e1307-e1309. doi: 10.4088/JCP.17f11998.
The action of memantine on N-methyl-D-aspartate (NMDA) glutamatergic receptors and the other pharmacodynamic actions of this drug suggest that it may benefit patients with schizophrenia. Many randomized controlled trials (RCTs) have examined this possibility. These RCTs have been meta-analyzed by at least 2 groups of authors. In one meta-analysis (8 RCTs, pooled N = 448), memantine (20 mg/d for 6-12 weeks) augmentation of antipsychotic drug therapy was found to attenuate the severity of negative symptoms and improve cognitive functioning; in both regards, the effect was large. Memantine was also associated with a small but statistically significant reduction in general psychopathology. Whereas memantine did not significantly attenuate positive symptom, depression, total psychopathology, and global illness ratings, it was also not associated with an increased risk of individual adverse events, discontinuation due to adverse events, or all-cause discontinuation. The findings of the other meta-analysis, which examined much the same body of literature, were largely similar. On the surface, these results suggest that memantine may be considered for the reduction of negative symptoms and cognitive impairment in schizophrenia. However, an examination of the individual RCTs and a careful look at the findings of the meta-analyses identify so many important concerns that it is probably premature to draw conclusions about the usefulness of memantine as an augmentation strategy in schizophrenia. At best, it may be stated that there is a signal that supports the study of memantine in schizophrenia patients who are specifically impaired by negative symptoms and cognitive complaints. This is a good example of a situation in which meta-analysis did not provide a trustable evidence-based interpretation of literature.
盐酸美金刚对 N-甲基-D-天冬氨酸（NMDA）谷氨酸能受体的作用以及该药的其他药效学作用表明，它可能使精神分裂症患者受益。许多随机对照试验（RCT）已经研究了这种可能性。这些 RCT 已经至少被 2 组作者进行了荟萃分析。在一项荟萃分析中（8 项 RCT，汇总 N = 448），发现美金刚（20 mg/d，治疗 6-12 周）作为增效治疗与抗精神病药物联合治疗可减轻阴性症状的严重程度并改善认知功能；在这两方面，其疗效均较大。美金刚还与一般精神病理学的小但具有统计学意义的降低相关。尽管美金刚并未显著减轻阳性症状、抑郁、总体精神病理学和总体疾病评分，但也与个体不良事件的风险增加、因不良事件而停药或所有原因停药无关。另一项荟萃分析检查了大致相同的文献，其结果基本相似。从表面上看，这些结果表明，可能会考虑将美金刚用于减少精神分裂症的阴性症状和认知障碍。然而，对单个 RCT 的检查以及对荟萃分析结果的仔细观察表明，存在许多重要问题，因此，关于美金刚作为精神分裂症增效策略的有用性得出结论可能还为时过早。充其量可以说，有一个信号支持对受阴性症状和认知障碍影响的精神分裂症患者进行美金刚研究。这是荟萃分析未能对文献进行可信的基于证据的解释的一个很好的例子。
