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

Acetylcysteine / therapeutic use Adult Bipolar Disorder / drug therapy Combined Modality Therapy / methods Dietary Supplements Double-Blind Method Female Humans Male Middle Aged Mitochondria / drug effects Treatment Outcome
Adjunctive Bipolar disorder Depression Mitochondria Nutraceutical Oxidative stress

Journal

BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723

Informations de publication

Date de publication:
25 01 2019
Historique:
received: 14 08 2018
accepted: 09 01 2019
entrez: 26 1 2019
pubmed: 27 1 2019
medline: 18 6 2019
Statut: epublish

Résumé

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. 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. 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. 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. ANZCTR ( ACTRN12612000830897 ).

Sections du résumé

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 ).

Identifiants

DOI: 10.1186/s12916-019-1257-1 PMID: 30678686 PMC: PMC6346513
pubmed: 30678686
doi: 10.1186/s12916-019-1257-1
pii: 10.1186/s12916-019-1257-1
pmc: PMC6346513
doi:

Substances chimiques

Acetylcysteine WYQ7N0BPYC

Banques de données

ANZCTR
['ACTRN12612000830897']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

18

Commentaires et corrections

Type : ErratumIn

Références

Neurosci Biobehav Rev. 2015 Aug;55:294-321
pubmed: 25957927
Aust N Z J Psychiatry. 2015 Jun;49(6):499-501
pubmed: 25931574
Biol Psychiatry. 2008 Sep 15;64(6):468-75
pubmed: 18534556
Neurosci Biobehav Rev. 2016 Sep;68:694-713
pubmed: 27377693
J Clin Psychiatry. 2016 Apr;77(4):e457-66
pubmed: 27137430
Schizophr Res. 2018 Sep;199:395-402
pubmed: 29588126
Nat Rev Neurosci. 2012 Apr 18;13(5):293-307
pubmed: 22510887
Braz J Psychiatry. 2015 Jan-Mar;37(1):3-12
pubmed: 25295681
Int Clin Psychopharmacol. 2015 Mar;30(2):59-66
pubmed: 25438027
Neurosci Biobehav Rev. 2017 Mar;74(Pt A):1-20
pubmed: 28093238
J Psychiatr Res. 2016 Mar;74:38-44
pubmed: 26736040
Psychiatry Res. 2018 Nov;269:658-672
pubmed: 30216918
BMC Med. 2015 Apr 01;13:68
pubmed: 25889215
J Clin Psychiatry. 2016 Nov;77(11):e1439-e1446
pubmed: 27736051

Auteurs

Michael Berk (M)

IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia. mikebe@barwonhealth.org.au.
Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Level 1 North, Main Block, Parkville, VIC, Australia. mikebe@barwonhealth.org.au.
Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, VIC, Australia. mikebe@barwonhealth.org.au.
Orygen, The National Centre of Excellence in Youth Mental Health, 35 Poplar Rd, Parkville, VIC, Australia. mikebe@barwonhealth.org.au.

Alyna Turner (A)

IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.
Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Level 1 North, Main Block, Parkville, VIC, Australia.
School of Medicine and Public Health, Faculty of Health and Medicine, the University of Newcastle, Callaghan, NSW, Australia.

Gin S Malhi (GS)

CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.
Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia.
ARCHI, Sydney Medical School Northern, University of Sydney, Sydney, NSW, Australia.

Chee H Ng (CH)

Department of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.

Susan M Cotton (SM)

Orygen, The National Centre of Excellence in Youth Mental Health, 35 Poplar Rd, Parkville, VIC, Australia.
Centre for Youth Mental Health, The University of Melbourne, 35 Poplar Rd, Parkville, VIC, Australia.

Seetal Dodd (S)

IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.
Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Level 1 North, Main Block, Parkville, VIC, Australia.
Centre for Youth Mental Health, The University of Melbourne, 35 Poplar Rd, Parkville, VIC, Australia.

Yuval Samuni (Y)

IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.

Michelle Tanious (M)

CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.

Claire McAulay (C)

CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia.

Nathan Dowling (N)

Department of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.

Jerome Sarris (J)

Department of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.
NICM, School of Health and Science, Western Sydney University, Campbelltown, NSW, Australia.

Lauren Owen (L)

School of Psychology, University of Central Lancashire, Preston, UK.

Astrid Waterdrinker (A)

Melbourne Health, 300 Grattan St, Melbourne, VIC, Australia.

Deidre Smith (D)

Department of Psychiatry, University of Melbourne, the Melbourne Clinic, 130 Church St Richmond, Melbourne, VIC, Australia.

Olivia M Dean (OM)

IMPACT Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, P.O. Box 291, Geelong, VIC, Australia.
Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Level 1 North, Main Block, Parkville, VIC, Australia.
Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, VIC, Australia.

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Classifications MeSH

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