Clinical Psychopharmacology and Neuroscience Papers in Press available online.

Mixed methods double-blind thematic analysis of a randomised controlled trial of adjunctive mitochondrial agents for bipolar depression
Samantha Emmi Russell 1, Anna Wrobel 1,2, Olivia M Dean 1,3, Michael Berk 1,2,4, Seetal Dodd 1,5, Chee H Ng 4, Gin S Malhi 6,7,8, Susan M Cotton 5,2, Jerome Sarris 4,9, Alyna Turner 1,10,*
1Deakin University, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, P.O. Box 281, Geelong, 3220, Australia, 2Orygen, The National Centre of Excellence in Youth Mental Health, 35 Poplar Rd, Parkville, 3052, Australia., 3Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, 30 Royal Parade, Parkville, 3052, Australia, 4Department of Psychiatry, University of Melbourne, The Melbourne Clinic, 130 Church St Richmond Australia 3121, 5Centre for Youth Mental Health, The University of Melbourne, 35 Poplar Rd, Parkville, 3052, Australia, 6The University of Sydney, Faculty of Medicine and Health, Northern Clinical School, Department of Psychiatry, Sydney, New South Wales, Australia, 7Academic Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW 2065 Australia, 8CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW 2065 Australia, 9NICM Health Research Institute, Western Sydney University, 158 Hawkesbury Rd, Westmead, NSW 2045, Australia, 10School of Medicine and Public Health, Faculty of Health, The University of Newcastle, Callaghan, 2308, Australia
Objective: There is often a shortfall in recovery following treatment for an episode of bipolar disorder (BD). Exploration of participant’s experience provides vital information to enhance statistical outcomes for novel therapy trials. This study used mixed-methods to explore participants’ experience of a trial testing N-acetyl cysteine (NAC) and mitochondrially active nutraceuticals for BD depression.
Method: Case report forms from a randomised controlled trial (RCT) of BD depression (n=148) were analysed using a pragmatic adaption of grounded theory and thematic analysis.
Results: Thematic analysis of 148 study participants indicated numerous changes in participant experience over time. For example, perceived environmental stressors reported by participants decreased over the trial in both treatment groups. Quantitative analysis of the themes revealed more positive theme reports in the combination treatment (CT) arm compared to the placebo arm and there were more negative themes identified in the placebo arm, compared to the NAC arm.
Conclusion: This approach revealed additional results not elucidated in the primary quantitative analysis. This emphasizes the value of mixed-methods research in capturing participants’ experiences in RCTs and detecting possible latent benefits and risks. Such methods can detect latent target signals in novel therapy trials conducted in BD and generate novel hypotheses.
Accepted Manuscript [Submitted on 2021-01-13, Accepted on 2021-02-06]