Effect of N-Acetylcysteine on Positive and Negative Syndrome Scale associated with Schizophrenia: A Meta-Analysis

Background and objective: N-acetylcysteine (NAC), a precursor of L-cysteine with antioxidant, anti-inflammatory and neurotropic effects, is a promising agent in alleviating symptoms associated with schizophrenia.  However, the role of NAC on parameters of Positive and Negative Syndrome Scale (PANSS) remain uncertain. This systematic review and meta-analysis explored the effect of NAC on parameters of PANSS in patients with chronic schizophrenia. Methods: We searchedPubmed/MEDLINE™, PsycNET™, PsycLIT™, Scopus™ and Google Scholar™  for studies on the effect of NAC on PANSS in patients with schizophrenia from inception to March 2019. We adopted medical and non-medical subjects headings (MeSH, non-MeSH) and several keywords, including  “NAC”, “N-acetylcysteine”, “N-acetyl cysteine”, “Acetylcysteine”, “N-Acetyl-L-cysteine”,  “schizophrenia”, “psychotic disorder”, “psychosis”, “schizoaffective” and “dementia praecox”. Results: We identified seven trials with274 patients meeting the inclusion criteria, with follow up between 8-52 weeks, and NAC supplementation between 1200-3600 mg/day. Significant improvements in PANSS were identified following NAC for total (SMD=-0.61, 95% CI = -0.91, -0.31 ; P<0.001), general (SMD = -0.58; 95% CI = -0.90, -0.26; P=0.0004); and negative (SMD = -0.56; 95% CI = -0.92, -0.21; P = 0.001) scores, respectively. No significant heterogeneity was found among studies. Significant reductions were observed following sub-group analysis in trials ≤ 24 weeks duration, with appreciable effect size for total (SMD= -0.83), general (SMD= -0.67) and negative (SMD=-1.09) scores. Conclusion: Supplementation of NAC was effective in alleviating PANSS symptoms associated with schizophrenia in trials ≤ 24 weeks duration. The use of NAC as an adjunct seems promising and further investigation is warranted to determine its precise role.