{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T09:07:16Z","timestamp":1793610436735,"version":"4.5.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T00:00:00Z","timestamp":1658275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["NHMRC GNT1098442"],"award-info":[{"award-number":["NHMRC GNT1098442"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Hypothesis<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Design<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Results<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with \u201cAustralian and New Zealand Clinical Trials\u201d on the 30 May, 2016 (Registration Number: ACTRN12615001273572).<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/schbul\/sbac065","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T17:28:49Z","timestamp":1658338129000},"page":"1263-1272","source":"Crossref","is-referenced-by-count":34,"title":["<i>N<\/i>-Acetylcysteine (NAC) in Schizophrenia Resistant to Clozapine: A Double-Blind, Randomized, Placebo-Controlled Trial Targeting Negative Symptoms"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-2159","authenticated-orcid":false,"given":"Erica","family":"Neill","sequence":"first","affiliation":[{"name":"Centre for Mental Health, Faculty of Health, Arts & Design, Swinburne University of Technology , Melbourne , Australia"},{"name":"Department of Mental Health, St Vincent\u2019s Hospital , Melbourne , 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