Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

doi:10.1186/1741-7015-10-91

BMC Med. 2012; 10: 91.

Published online 2012 August 14. doi: 10.1186/1741-7015-10-91

PMCID: PMC3482580

Maintenance N-acetyl cysteine treatment for bipolar disorder: A double-blind randomized placebo controlled trial

Michael Berk,^1,^2,^3,^4,⁵ Olivia M Dean,^1,^4,⁵ Sue M Cotton,^2,³ Clarissa S Gama,⁶ Flavio Kapczinski,⁶ Brisa Fernandes,^7,⁸ Kristy Kohlmann,⁴ Susan Jeavons,⁴ Karen Hewitt,⁴ Kirsteen Moss,^9,¹⁰ Christine Allwang,^9,^10,¹¹ Ian Schapkaitz,⁴ Heidi Cobb,⁹ Ashley I Bush,⁴ Seetal Dodd,^1,⁵ and Gin S Malhi^8,⁹

¹Deakin University, School of Medicine, Barwon Health, P.O. Box 291, Geelong, 3220, Australia

²Orygen Youth Health Research Centre, 35 Poplar Rd, Parkville, 3052, Australia

³Centre of Youth Mental Health, University of Melbourne, 35 Poplar Rd, Parkville, 3052, Australia

⁴Mental Health Research Institute, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, 3052, Parkville, Australia

⁵University of Melbourne, Department of Psychiatry, Level 1 North, Main Block, Royal Melbourne Hospital, Parkville, 3052, Australia

⁶Laboratory of Molecular Psychiatry, INCT for Translational Medicine, CNPq. Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, 90010-000, Brazil

⁷Post-graduate Program in Biological Sciences: Biochemistry, Federal University of Rio Grande do Sul - UFRGS -, Porto Alegre, 90035-000, Brazil

⁸Laboratory of Calcium Binding Proteins in the Central Nervous System, Department of Biochemistry, Federal University of Rio Grande do Sul - UFRGS -, Porto Alegre, 90035-000, Brazil

⁹Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, 2006, Australia

¹⁰CADE Clinic, Department of Psychiatry, Level 5 Building 36 Royal North Shore Hospital, St. Leonards, 2065, Australia

¹¹Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar der TU, München, Ismaninger Str. 22, 81675, Münich, Germany

Corresponding author.

Michael Berk: mikebe/at/barwonhealth.org.au; Olivia M Dean: oliviad/at/barwonhealth.org.au; Sue M Cotton: smcotton/at/unimelb.edu.au; Clarissa S Gama: csgama/at/yahoo.com; Flavio Kapczinski: kapcz/at/terra.com.br; Brisa Fernandes: brisasf/at/gmail.com; Kristy Kohlmann: kristykohlmann/at/gmail.com; Susan Jeavons: sue/at/qdt.com.au; Karen Hewitt: karenhe/at/barwonhealth.org.au; Kirsteen Moss: kirsteen.hede/at/gmail.com; Christine Allwang: christine.allwang/at/gmx.de; Ian Schapkaitz: schapk2/at/bigpond.net.au; Heidi Cobb: heidicobb/at/hotmail.co.uk; Ashley I Bush: ashleyib/at/unimelb.edu.au; Seetal Dodd: seetald/at/barwonhealth.org.au; Gin S Malhi: gmalhi/at/med.usyd.edu.au

Received May 7, 2012; Accepted August 14, 2012.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract

Background

N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.

Method

The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.

Results

There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.

Conclusions

There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations.

Trial Registration

The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).

Keywords: N-acetyl cysteine, depression, bipolar disorder, maintenance, mania, oxidative

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