title: Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression.
abstract: OBJECTIVE
  Bipolar disorder places a significant burden on individuals, caregivers and family, and the broader community. Current treatments are believed to be more effective against manic symptoms, leaving a shortfall in recovery during the depressive phase of the illness. The current study draws on recent evidence suggesting that, in addition to increased oxidative load, alterations in mitochondrial function occur in bipolar disorder.
  
  
  METHODS
  This 16-week study aims to explore the potential benefits of N-acetylcysteine (NAC) alone or in combination (CT) with selected nutraceuticals believed to enhance mitochondrial function. The study includes adults diagnosed with bipolar disorder currently experiencing an episode of depression. Participants are asked to take NAC, CT, or placebo in addition to any usual treatments. A post-discontinuation visit is conducted 4 weeks following the treatment phase.
  
  
  RESULTS
  The primary outcome of the study will be mean change on the Montgomery-Asberg Depression Rating Scale. Secondary outcomes include functioning, substance use, mania ratings, and quality of life. Blood samples will be collected at baseline and week 16 to explore biochemical alterations following treatment.
  
  
  CONCLUSIONS
  This study may provide a novel adjunctive treatment for bipolar depression. Analysis of biological samples may assist in understanding the therapeutic benefits and the underlying etiology of bipolar depression.
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trial Registry ACTRN12612000830897.
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Dean
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.
authors.forename: Alyna
authors.initials: A
authors.lastname: Turner
authors.affiliation: Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Gin S
authors.initials: GS
authors.lastname: Malhi
authors.affiliation: Department of Psychiatry University of Melbourne, Melbourne, Australia.
authors.forename: Chee
authors.initials: C
authors.lastname: Ng
authors.affiliation: Orygen Youth Health Research Centre, Melbourne, Australia.
authors.forename: Sue M
authors.initials: SM
authors.lastname: Cotton
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.
authors.forename: Seetal
authors.initials: S
authors.lastname: Dodd
authors.affiliation: University of Melbourne, Melbourne, Australia.
authors.forename: Jerome
authors.initials: J
authors.lastname: Sarris
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Samuni
authors.affiliation: Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Tanious
authors.affiliation: Department of Psychiatry University of Melbourne, Melbourne, Australia.
authors.forename: Nathan
authors.initials: N
authors.lastname: Dowling
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.
authors.forename: Astrid
authors.initials: A
authors.lastname: Waterdrinker
authors.affiliation: Department of Psychiatry University of Melbourne, Melbourne, Australia.
authors.forename: Deidre
authors.initials: D
authors.lastname: Smith
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D003866:Depressive Disorder / Q000628:therapy*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D028361:Mitochondrial Diseases / Q000628:therapy*; D010919:Placebos / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D013997:Time Factors; D016896:Treatment Outcome; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use; D024483:Vitamin K 3 / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D010919:Placebos; D014815:Vitamins; D014451:Ubiquinone; D024483:Vitamin K 3; C036619:idebenone; D000111:Acetylcysteine