N-Acetyl cysteine as a glutathione precursor for schizophrenia : a double blind, randomized, placebo-controlled trial

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. and Bush, Ashley I. 2008, N-Acetyl cysteine as a glutathione precursor for schizophrenia : a double blind, randomized, placebo-controlled trial, Biological psychiatry, vol. 64, no. 5, pp. 361-368, doi: 10.1016/j.biopsych.2008.03.004.

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Title N-Acetyl cysteine as a glutathione precursor for schizophrenia : a double blind, randomized, placebo-controlled trial
Author(s) Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Copolov, David
Dean, OliviaORCID iD for Dean, Olivia orcid.org/0000-0002-2776-3935
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.
Journal name Biological psychiatry
Volume number 64
Issue number 5
Start page 361
End page 368
Total pages 8
Publisher Elsevier
Place of publication Philadelphia, Pa.
Publication date 2008-09-01
ISSN 0006-3223
Keyword(s) adjunct therapy
clinical trials
n-acetyl cysteine
Summary 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.

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.
Language eng
DOI 10.1016/j.biopsych.2008.03.004
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, Society of Biological Psychiatry
Persistent URL http://hdl.handle.net/10536/DRO/DU:30035460

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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