N-acetylcysteine (NAC) in schizophrenia resistant to clozapine : a double blind randomised placebo controlled trial targeting negative symptoms

Susan L. Rossell; Paul S. Francis; Cherrie Galletly; Anthony Harris; Dan Siskind; Michael Berk; Kiymet Bozaoglu; Frances Dark; Olivia Dean; Dennis Liu; Denny Meyer; Erica Neill; Andrea Phillipou; Jerome Sarris; David J. Castle

doi:10.1186/s12888-016-1030-3

N-acetylcysteine (NAC) in schizophrenia resistant to clozapine : a double blind randomised placebo controlled trial targeting negative symptoms

Susan L. Rossell, Paul S. Francis, Cherrie Galletly, Anthony Harris, Dan Siskind, Michael Berk, Kiymet Bozaoglu, Frances Dark, Olivia Dean, Dennis Liu, Denny Meyer, Erica Neill, Andrea Phillipou, Jerome Sarris, David J. Castle

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Abstract

Background: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. Methods: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. Discussion: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a 'go to' adjunct in patients that are only partly responsive to clozapine. Trial registration: Australian and New Zealand Clinical Trials Registration Number: Current Randomised Controlled Trial ACTRN12615001273572. The date of registration 23 November 2015.

Original language	English
Article number	320
Number of pages	9
Journal	BMC Psychiatry
Volume	16
DOIs	https://doi.org/10.1186/s12888-016-1030-3
Publication status	Published - 2016

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© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Keywords

N, acetyl cysteine
clozapine
mental illness
randomized controlled trials
schizophrenia

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N-acetylcysteine_Open access

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Rossell, S. L., Francis, P. S., Galletly, C., Harris, A., Siskind, D., Berk, M., Bozaoglu, K., Dark, F., Dean, O., Liu, D., Meyer, D., Neill, E., Phillipou, A., Sarris, J., & Castle, D. J. (2016). N-acetylcysteine (NAC) in schizophrenia resistant to clozapine : a double blind randomised placebo controlled trial targeting negative symptoms. BMC Psychiatry, 16, Article 320. https://doi.org/10.1186/s12888-016-1030-3

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title = "N-acetylcysteine (NAC) in schizophrenia resistant to clozapine : a double blind randomised placebo controlled trial targeting negative symptoms",

abstract = "Background: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. Methods: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. Discussion: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a 'go to' adjunct in patients that are only partly responsive to clozapine. Trial registration: Australian and New Zealand Clinical Trials Registration Number: Current Randomised Controlled Trial ACTRN12615001273572. The date of registration 23 November 2015.",

keywords = "N, acetyl cysteine, clozapine, mental illness, randomized controlled trials, schizophrenia",

author = "Rossell, {Susan L.} and Francis, {Paul S.} and Cherrie Galletly and Anthony Harris and Dan Siskind and Michael Berk and Kiymet Bozaoglu and Frances Dark and Olivia Dean and Dennis Liu and Denny Meyer and Erica Neill and Andrea Phillipou and Jerome Sarris and Castle, {David J.}",

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Rossell, SL, Francis, PS, Galletly, C, Harris, A, Siskind, D, Berk, M, Bozaoglu, K, Dark, F, Dean, O, Liu, D, Meyer, D, Neill, E, Phillipou, A, Sarris, J & Castle, DJ 2016, 'N-acetylcysteine (NAC) in schizophrenia resistant to clozapine : a double blind randomised placebo controlled trial targeting negative symptoms', BMC Psychiatry, vol. 16, 320. https://doi.org/10.1186/s12888-016-1030-3

TY - JOUR

T1 - N-acetylcysteine (NAC) in schizophrenia resistant to clozapine : a double blind randomised placebo controlled trial targeting negative symptoms

AU - Rossell, Susan L.

AU - Francis, Paul S.

AU - Galletly, Cherrie

AU - Harris, Anthony

AU - Siskind, Dan

AU - Berk, Michael

AU - Bozaoglu, Kiymet

AU - Dark, Frances

AU - Dean, Olivia

AU - Liu, Dennis

AU - Meyer, Denny

AU - Neill, Erica

AU - Phillipou, Andrea

AU - Sarris, Jerome

AU - Castle, David J.

PY - 2016

Y1 - 2016

N2 - Background: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. Methods: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. Discussion: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a 'go to' adjunct in patients that are only partly responsive to clozapine. Trial registration: Australian and New Zealand Clinical Trials Registration Number: Current Randomised Controlled Trial ACTRN12615001273572. The date of registration 23 November 2015.

AB - Background: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60 % of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered 'clozapine resistant'. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. Methods: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2 g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. Discussion: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a 'go to' adjunct in patients that are only partly responsive to clozapine. Trial registration: Australian and New Zealand Clinical Trials Registration Number: Current Randomised Controlled Trial ACTRN12615001273572. The date of registration 23 November 2015.

KW - N, acetyl cysteine

KW - clozapine

KW - mental illness

KW - randomized controlled trials

KW - schizophrenia

UR - http://handle.westernsydney.edu.au:8081/1959.7/uws:39412

U2 - 10.1186/s12888-016-1030-3

DO - 10.1186/s12888-016-1030-3

M3 - Article

SN - 1471-244x

VL - 16

JO - BMC Psychiatry

JF - BMC Psychiatry

M1 - 320

ER -

N-acetylcysteine (NAC) in schizophrenia resistant to clozapine : a double blind randomised placebo controlled trial targeting negative symptoms

Abstract

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