Berk Michael, Copolov David, Dean Olivia, Lu Kristy, Jeavons Sue, Schapkaitz Ian, Anderson-Hunt Murray, Judd Fiona, Katz Fiona, Katz Paul, Ording-Jespersen Sean, Little John, Conus Philippe, Cuenod Michel, Do Kim Q, Bush Ashley I
The Mental Health Research Institute of Victoria, Parkville, Australia.
Biol Psychiatry. 2008 Sep 1;64(5):361-8. doi: 10.1016/j.biopsych.2008.03.004. Epub 2008 Apr 23.
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 (1 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.
A randomized, multicenter, double-blind, placebo-controlled 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.
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 = .009], PANSS negative [mean difference -1.83 (95% confidence interval: -3.33, -.32), p = .018], and PANSS general [-2.79 (-5.38, -.20), p = .035], CGI-Severity (CGI-S) [-.26 (-.44, -.08), p = .004], and CGI-Improvement (CGI-I) [-.22 (-.41, -.03), p = .025] 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.
These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.
精神分裂症患者大脑中的谷胱甘肽水平降低，这是一种通常为慢性且治疗难治的疾病。N-乙酰半胱氨酸（NAC）可提高啮齿动物大脑中的谷胱甘肽水平。本研究旨在评估口服NAC（每日两次，每次1克口服）作为维持药物的附加治疗在24周内治疗慢性精神分裂症的安全性和有效性。
一项随机、多中心、双盲、安慰剂对照研究。主要观察指标是阳性和阴性症状量表（PANSS）及其组成部分相对于基线的变化。次要观察指标包括临床总体印象（CGI）严重程度和改善量表，以及总体功能和锥体外系评定量表。评估了4周治疗停药后的变化。140名正在接受维持性抗精神病药物治疗的慢性精神分裂症患者被随机分组；84人完成了治疗。
意向性分析显示，在研究期间，接受NAC治疗的受试者在PANSS总分[-5.97（-10.44，-1.51），p = 0.009]、PANSS阴性[平均差异-1.83（95%置信区间：-3.33，-0.32），p = 0.018]、PANSS一般[-2.79（-5.38，-0.20），p = 组间差异-2.79（-5.38，-0.20），p = 0.035]、CGI严重程度（CGI-S）[-0.26（-0.44，-0.08），p = 0.004]和CGI改善（CGI-I）[-0.22（-0.41，-0.03），p = 0.025]评分方面比接受安慰剂治疗的受试者改善更多。PANSS阳性分量表未见显著变化。N-乙酰半胱氨酸治疗还与静坐不能的改善相关（p = 0.022）。终点时的效应量与中度获益一致。
这些数据表明，辅助使用NAC作为慢性精神分裂症的一种安全且中度有效的增效策略具有潜力。
