The Cognitive and Negative Symptoms in Schizophrenia, Trial (CONSIST): The efficacy of glutamatergic agents for negative symptoms and cognitive impairments
The Cognitive and Negative Symptoms in Schizophrenia, Trial (CONSIST): The efficacy of glutamatergic agents for negative symptoms and cognitive impairments
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DOI：
10.1176/appi.ajp.2007.06081358
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发表时间：
2007-10-01
影响因子：
17.7
通讯作者：
Carpenter, William T.
中科院分区：
文献类型：
--
作者：
Buchanan, Robert W.;Javitt, Daniel C.;Carpenter, William T.
目的：精神分裂症患者常出现阴性症状和认知障碍，目前尚无有效的治疗方法。作用于N-甲基-D-天冬氨酸(NMDA)谷氨酸能受体甘氨酸部位的药物被认为是治疗中重度阴性症状和认知障碍的有希望的药物。方法：精神分裂症中的认知和阴性症状试验(STUST)是一项为期16周的双盲、双模拟、平行分组、随机临床试验，辅助性甘氨酸、D-环丝氨酸或安慰剂在美国的四个地点和以色列的一个地点进行。参与者是157名住院和门诊患者，他们符合DSM-IV精神分裂症或分裂情感障碍标准，以及无明显阳性、抑郁或锥体外系症状的中度至重度阴性症状的回顾和前瞻性标准。主要观察指标为阴性症状评定量表的平均变化率(SANS)总分和平均认知领域z分的变化。结果：甘氨酸和安慰剂组或D-环丝氨酸组和安慰剂组SANS总分的变化没有显著差异。预先指定的逐点逐次治疗交互作用的测试在后组试验中具有重要意义。与接受安慰剂的患者相比，接受D-环丝氨酸治疗的患者SANS总分有一个更大的降低。与甘氨酸患者相比，安慰剂患者的SANS总分有更大的下降。甘氨酸和安慰剂或D-环丝氨酸和安慰剂受试者在平均认知z得分上没有显著差异。结论：研究结果表明，甘氨酸和D-环丝氨酸都不是治疗阴性症状或认知障碍的普遍有效的治疗方案。
objective: Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known. Agents that act at the glycine site of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments.Method: The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) was a 16-week double-blind, double-dummy, parallel group, randomized clinical trial of adjunctive glycine, D-cycloserine, or placebo conducted at four sites in the United States and one site in Israel. The participants were 157 inpatients and outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospective criteria for moderate to severe negative symptoms without marked positive, depressive, or extrapyramidal symptoms. The primary outcome measures were the average "rate of change" of Scale for the Assessment of Negative Symptoms (SANS) total scores and change in the average cognitive domain z scores.Results: There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects. A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests. One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo. A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients. There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score.Conclusions: The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments.