de Lucena David, Fernandes Brisa Simões, Berk Michael, Dodd Seetal, Medeiros Dalton W, Pedrini Mariana, Kunz Mauricio, Gomes Fabiano Alves, Giglio Larriany F, Lobato Maria Inês, Belmonte-de-Abreu Paulo Silva, Gama Clarissa Severino
Programa de Pós-Graduação em Medicina: Psiquiatria, Universidade Federal do Rio Grande do Sul, Brazil.
J Clin Psychiatry. 2009 Oct;70(10):1416-23. doi: 10.4088/JCP.08m04935gry.
Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia.
In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS).
Twenty-one participants completed the study and were used in the analysis. Significant improvement (P < .01) on the total BPRS score, its subscales of positive (effect size [ES] = -1.38) and negative (ES = -3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed.
Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients.
clinicaltrials.gov Identifier: NCT00757978.
谷氨酸调节异常可能参与精神分裂症的神经病理学过程，主要通过N-甲基-D-天冬氨酸（NMDA）受体功能障碍。美金刚是一种经美国食品药品监督管理局（FDA）批准用于治疗中度至重度阿尔茨海默病的药物，它作为一种弱效非选择性NMDA受体拮抗剂发挥作用。本研究的目的是检验美金刚作为难治性精神分裂症患者氯氮平辅助治疗的疗效。
在这项双盲、安慰剂对照研究中，根据《精神疾病诊断与统计手册》第四版（DSM-IV）临床标准确定的难治性精神分裂症门诊患者，于2005年3月至2008年2月被随机分配，除氯氮平外，分别接受20mg/d美金刚（n = 10）或安慰剂（n = 11）治疗，为期12周。主要结局指标是18项简明精神病评定量表（BPRS）总分以及BPRS阳性和阴性症状分量表得分。次要结局指标包括临床总体印象量表（CGI）测量的疾病总体严重程度、简易精神状态检查表（MMSE）评估的认知功能以及辛普森-安格斯量表（SAS）评估的锥体外系症状。
21名参与者完成了研究并纳入分析。与安慰剂相比，美金刚治疗组在BPRS总分、阳性（效应量[ES] = -1.38）和阴性（ES = -3.33）症状分量表得分、CGI得分（ES = 1.56）以及MMSE得分方面均有显著改善（P <.01）。未观察到锥体外系症状有显著变化。
难治性精神分裂症患者在氯氮平治疗基础上加用美金刚与阴性和阳性症状的改善相关。
clinicaltrials.gov标识符：NCT00757978。
