title: N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial.
abstract: 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 (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.
  
  
  METHODS
  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.
  
  
  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 = .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.
  
  
  CONCLUSIONS
  These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia.
authors.affiliation: The Mental Health Research Institute of Victoria, Parkville, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: David
authors.initials: D
authors.lastname: Copolov
authors.forename: Olivia
authors.initials: O
authors.lastname: Dean
authors.forename: Kristy
authors.initials: K
authors.lastname: Lu
authors.forename: Sue
authors.initials: S
authors.lastname: Jeavons
authors.forename: Ian
authors.initials: I
authors.lastname: Schapkaitz
authors.forename: Murray
authors.initials: M
authors.lastname: Anderson-Hunt
authors.forename: Fiona
authors.initials: F
authors.lastname: Judd
authors.forename: Fiona
authors.initials: F
authors.lastname: Katz
authors.forename: Paul
authors.initials: P
authors.lastname: Katz
authors.forename: Sean
authors.initials: S
authors.lastname: Ording-Jespersen
authors.forename: John
authors.initials: J
authors.lastname: Little
authors.forename: Philippe
authors.initials: P
authors.lastname: Conus
authors.forename: Michel
authors.initials: M
authors.lastname: Cuenod
authors.forename: Kim Q
authors.initials: KQ
authors.lastname: Do
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D017063:Outcome Assessment, Health Care / Q000379:methods; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*
chemical_list: D016166:Free Radical Scavengers; D000111:Acetylcysteine