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

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). [ABSTRACT FROM AUTHOR]