N-acetyl cysteine as a glutathione precursor for schizophrenia - A double-blind, randomized, placebo-controlled trial
N-acetyl cysteine as a glutathione precursor for schizophrenia - A double-blind, randomized, placebo-controlled trial
复制标题
DOI：
10.1016/j.biopsych.2008.03.004
复制
发表时间：
2008-09-01
影响因子：
10.6
通讯作者：
Bush, Ashley I.
中科院分区：
文献类型：
--
作者：
Berk, Michael;Copolov, David;Bush, Ashley I.
背景：精神分裂症患者的脑谷胱甘肽水平降低，精神分裂症是一种慢性且难治的疾病。N-乙酰半胱氨酸（NAC）增加啮齿动物脑谷胱甘肽。本研究旨在评价口服NAC（1 g，每日2次[b.i.d.]）的安全性和有效性。作为维持药物的添加治疗，治疗慢性精神分裂症24周。方法：一项随机、多中心、双盲、安慰剂对照主导的研究。主要读数是阳性和阴性症状量表（PANSS）及其组分较基线的变化。次要读数包括临床总体印象（CGI）严重程度和改善量表，以及一般功能和锥体外系评定量表。评价了治疗中止4周后的变化。140例慢性精神分裂症患者接受随机化的抗精神病药物维持治疗，84例完成治疗。意向治疗分析显示，在研究期间，接受NAC治疗的受试者在PANSS总评分方面的改善程度高于接受安慰剂治疗的受试者[-5.97（-10.44，-1.51），p = .0091，PANSS阴性[平均差异-1.83（95%置信区间：-3.33，-.32），p = .0181，PANSS一般[-2.79（-5.38，-.20），p = .035]，CGI-严重度（CGI-S）[-.26（-.44，-.08），p = .0041，和CGI-改善（CGI-I）[-.22（-.41，-.03），p = .0251评分。PANSS阳性子量表未观察到显著变化。N-乙酰半胱氨酸治疗也与静坐不能的改善相关（p = 0.022）。在终点的效果大小是一致的中度benefits.Conclusions：这些数据表明，连续NAC有潜力作为一个安全和适度有效的增强策略慢性精神分裂症。
Background: Brain glutathione levels are decreased in schizophrenia, a disorder that often is chronic and refractory to treatment. N-acetyl cysteine (NAC) increases brain glutathione in rodents. This study was conducted to evaluate the safety and effectiveness of oral NAC (I g orally twice daily [b.i.d.]) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period.Methods: A randomized, multicenter, double-blind, placebo-control led study. The primary readout was change from baseline on the Positive and Negative Symptoms Scale (PANSS) and its components. Secondary readouts included the Clinical Global Impression (CGI) Severity and Improvement scales, as well as general functioning and extrapyramidal rating scales. Changes following a 4-week treatment discontinuation were evaluated. One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were randomized; 84 completed treatment.Results: Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [-5.97 (-10.44, -1.51), p = .0091, PANSS negative [mean difference -1.83 (95% confidence interval: -3.33, -.32), p = .0181, and PANSS general [-2.79 (-5.38, -.20), p = .035], CGI-Severity (CGI-S) [-.26 (-.44, -.08),p = .0041, and CGI-Improvement (CGI-I) [-.22 (-.41, -.03), p = .0251 scores. No significant change on the PANSS positive subscale was seen. N-acetyl cysteine treatment also was associated with an improvement in akathisia (p = .022). Effect sizes at end point were consistent with moderate benefits.Conclusions: These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.