A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo

Berk, Michael, Turner, Alyna, Malhi, Gin S, Ng, Chee H, Cotton, Susan M, Dodd, Seetal, Samuni, Yuval, Tanious, Michelle, McAulay, Claire, Dowling, Nathan, Sarris, Jerome, Owen, Lauren, Waterdrinker, Astrid, Smith, Deidre and Dean, Olivia M 2019, A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo, BMC medicine, vol. 17, pp. 1-11, doi: 10.1186/s12916-019-1257-1.

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Title A randomised controlled trial of a mitochondrial therapeutic target for bipolar depression: mitochondrial agents, N-acetylcysteine, and placebo
Author(s) Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Turner, AlynaORCID iD for Turner, Alyna orcid.org/0000-0001-7389-2546
Malhi, Gin S
Ng, Chee H
Cotton, Susan M
Dodd, SeetalORCID iD for Dodd, Seetal orcid.org/0000-0002-7918-4636
Samuni, Yuval
Tanious, Michelle
McAulay, Claire
Dowling, Nathan
Sarris, Jerome
Owen, Lauren
Waterdrinker, Astrid
Smith, Deidre
Dean, Olivia MORCID iD for Dean, Olivia M orcid.org/0000-0002-2776-3935
Journal name BMC medicine
Volume number 17
Article ID 18
Start page 1
End page 11
Total pages 11
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2019-01-25
ISSN 1741-7015
Keyword(s) Adjunctive
Bipolar disorder
Oxidative stress
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Summary BACKGROUND: A phasic dysregulation of mitochondrial bioenergetics may operate in bipolar disorder, increased in mania and decreased in depression. We aimed to examine efficacy of two add-on treatments in bipolar depression: N-acetylcysteine (NAC) and NAC with a combination of nutraceutical agents that may increase mitochondrial biogenesis. METHODS: A three-arm 16-week, double-blind, randomised, placebo-controlled trial, adjunctive to usual treatment, was conducted. Participants (n = 181) with bipolar disorder and current depressive symptoms were randomised to 2000 mg/day NAC (n = 59), 2000 mg/day NAC with the combination nutraceutical treatment (CT, n = 61), or placebo (n = 61). The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to week 16. Young Mania Rating Scale, Clinical Global Impression (CGI)-Improvement and CGI-Severity scales, Patient Global Impression scale, Social and Occupational Functioning Assessment Scale (SOFAS), Longitudinal Interval Follow-Up Evaluation - Range of Impaired Functioning Tool (LIFE-RIFT), and Quality of Life Enjoyment, and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) were secondary outcomes. RESULTS: One hundred forty-eight participants had post-randomisation data and were analysed (NAC = 52, CT = 47, Placebo = 49). No between-group differences were found for the rate of change between baseline and 16 weeks on any of the clinical and functioning variables. Improvements in MADRS, BDRS, SOFAS, and LIFE-RIFT scores from baseline to the week 20 post-discontinuation visit were significantly greater in the CT group compared to those in the placebo. At week 20, the CGI-I was significantly lower in the CT group versus placebo. Gastrointestinal symptoms were significantly greater in the NAC than in the placebo group. CONCLUSIONS: These overall negative results, with no significant differences between groups detected at the primary outcome but some positive secondary signals, suggest either delayed benefit of the combination or an improvement of symptoms on withdrawal which warrants further exploration regarding the composition, mechanisms, and application of mitochondrial agents in illnesses characterised by mitochondrial dysfunction. TRIAL REGISTRATION: ANZCTR ( ACTRN12612000830897 ).
Language eng
DOI 10.1186/s12916-019-1257-1
Field of Research 11 Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2019, The Author(s)
Persistent URL http://hdl.handle.net/10536/DRO/DU:30117145

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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