Andrade Chittaranjan
Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India.
J Clin Psychiatry. 2022 Sep 26;83(5):22f14664. doi: 10.4088/JCP.22f14664.
-acetylcysteine (NAC) augmentation of antipsychotic medication is one of very many antipsychotic augmentation strategies that have been studied in schizophrenia. A recent systematic review and meta-analysis of 6 randomized controlled trials (RCTs) found that NAC (median dose, 2,000 mg/d) improved several clinical outcomes at different time points with medium to large effect sizes; however, many of the significant findings in this meta-analysis are suspect because they appeared to be influenced by 2 short-term (8-week) RCTs with outlying characteristics. Important findings not influenced by the 2 outlying RCTs were significant attenuation by NAC of negative symptom (3 RCTs) and total psychopathology (2 RCTs) ratings at ≥ 24 weeks and improvement in working memory but not processing speed (3 RCTs). Of these findings, reduction in psychopathology ratings, though statistically significant, appeared too small to be clinically meaningful. Finally, a newly published, moderately large RCT of NAC (2,000 mg/d) in schizophrenia patients refractory to clozapine found that 1 year of treatment with NAC did not outperform placebo for any clinical, cognitive, or quality of life outcome. The take-home message is that it is premature to recommend the use of NAC to treat schizophrenia for any target domain in routine clinical practice and that there does not appear to be a role for NAC for any indication in clozapine-refractory schizophrenia. However, it may be worth studying whether NAC, dosed at 2,000 mg/d or higher for 6 months or longer, improves functional outcomes in schizophrenia.
N-乙酰半胱氨酸（NAC）增强抗精神病药物治疗是众多已在精神分裂症中研究过的抗精神病药物增效策略之一。最近一项对6项随机对照试验（RCT）的系统评价和荟萃分析发现，NAC（中位剂量，2000毫克/天）在不同时间点改善了多项临床结局，效应大小为中到大型；然而，该荟萃分析中的许多显著发现值得怀疑，因为它们似乎受到两项具有异常特征的短期（8周）RCT的影响。不受这两项异常RCT影响的重要发现包括，在≥24周时，NAC显著减轻了阴性症状（3项RCT）和总体精神病理学（2项RCT）评分，改善了工作记忆，但未改善处理速度（3项RCT）。在这些发现中，精神病理学评分的降低虽然具有统计学意义，但似乎太小，不具有临床意义。最后，一项新发表的、规模适中的关于NAC（2000毫克/天）治疗对氯氮平难治的精神分裂症患者的RCT发现，NAC治疗1年在任何临床、认知或生活质量结局方面均未优于安慰剂。关键信息是，在常规临床实践中，就任何目标领域而言，推荐使用NAC治疗精神分裂症还为时过早，而且在对氯氮平难治的精神分裂症中，NAC似乎对任何适应症都没有作用。然而，研究NAC以2000毫克/天或更高剂量服用6个月或更长时间是否能改善精神分裂症的功能结局可能是值得的。
