N-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms.

Abstract

BACKGROUND AND HYPOTHESIS:

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC).

STUDY DESIGN:

A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks.

STUDY RESULTS:

NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11; Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26).

CONCLUSIONS:

NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with "Australian and New Zealand Clinical Trials" on the 30 May, 2016 (Registration Number: ACTRN12615001273572).

• Authors: Erica Neill, Susan L Rossell, Caitlin Yolland, Denny Meyer, Cherrie Galletly, Anthony Harris, Dan Siskind, Michael Berk, Kiymet Bozaoglu, Frances Dark, Olivia M Dean, Paul S Francis, Dennis Liu, Andrea Phillipou, Jerome Sarris, David J Castle
• Journal: Schizophrenia bulletin (Schizophr Bull) Vol. 48 Issue 6 Pg. 1263-1272 (11 18 2022) ISSN: 1745-1701 [Electronic] United States
• PMID: 35857752 (Publication Type: Randomized Controlled Trial, Multicenter Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Chemical References

• Clozapine
• Acetylcysteine
• Antipsychotic Agents

Topics

• Humans
• Clozapine (adverse effects)
• Schizophrenia (drug therapy, chemically induced)
• Acetylcysteine (pharmacology)
• Quality of Life (psychology)
• Treatment Outcome
• Australia
• Antipsychotic Agents (adverse effects)
• Double-Blind Method