title: The Beyond Ageing Project Phase 2--a double-blind, selective prevention, randomised, placebo-controlled trial of omega-3 fatty acids and sertraline in an older age cohort at risk for depression: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Late-life depression is associated with high rates of morbidity, premature mortality, disability, functional decline, caregiver burden and increased health care costs. While clinical and public health approaches are focused on prevention or early intervention strategies, the ideal method of intervention remains unclear. No study has set out to evaluate the role of neurobiological agents in preventing depressive symptoms in older populations at risk of depression.
  
  
  METHODS
  Subjects with previously reported sub-threshold depressive symptoms, aged 60 to 74 years, will be screened to participate in a single-centre, double-blind, randomised controlled trial with three parallel groups involving omega-3 fatty acid supplementation or sertraline hydrochloride, compared with matching placebo. Subjects will be excluded if they have current depression or suicide ideation; are taking antidepressants or any supplement containing omega-3 fatty acid; or have a prior history of stroke or other serious cerebrovascular or cardiovascular disease, neurological disease, significant psychiatric disease (other than depression) or neurodegenerative disease. The trial will consist of a 12 month treatment phase with follow-up at three months and 12 months to assess outcome events. At three months, subjects will undergo structural neuroimaging to assess whether treatment effects on depressive symptoms correlate with brain changes. Additionally, proton spectroscopy techniques will be used to capture brain-imaging markers of the biological effects of the interventions. The trial will be conducted in urban New South Wales, Australia, and will recruit a community-based sample of 450 adults. Using intention-to-treat methods, the primary endpoint is an absence of clinically relevant depression scores at 12 months between the omega-3 fatty acid and sertraline interventions and the placebo condition.
  
  
  CONCLUSIONS
  The current health, social and economic costs of late-life depression make prevention imperative from a public health perspective. This innovative trial aims to address the long-neglected area of prevention of depression in older adults. The interventions are targeted to the pathophysiology of disease, and regardless of the effect size of treatment, the outcomes will offer major scientific advances regarding the neurobiological action of these agents. The main results are expected to be available in 2017.
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trials Registry ACTRN12610000032055 (12 January 2010).
authors.affiliation: Healthy Brain Ageing Program, Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia. nicole.cockayne@sydney.edu.au.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Cockayne
authors.affiliation: Healthy Brain Ageing Program, Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia. shantel.duffy@sydney.edu.au.
authors.forename: Shantel L
authors.initials: SL
authors.lastname: Duffy
authors.affiliation: Healthy Brain Ageing Program, Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia. rosalind.bonomally@sydney.edu.au.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Bonomally
authors.affiliation: Healthy Brain Ageing Program, Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia. amelia.english@sydney.edu.au.
authors.forename: Amelia
authors.initials: A
authors.lastname: English
authors.affiliation: Orygen - The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Locked Bag 10, Parkville, VIC, 3052, Australia. paul.amminger@orygen.org.au.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Amminger
authors.affiliation: Orygen - The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Locked Bag 10, Parkville, VIC, 3052, Australia. Andrew.Mackinnon@unimelb.edu.au.
authors.forename: Andrew
authors.initials: A
authors.lastname: Mackinnon
authors.affiliation: Black Dog Institute, University of New South Wales, Hospital Road, Prince of Wales Hospital, Randwick, NSW, 2031, Australia. h.christensen@blackdog.org.au.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Christensen
authors.affiliation: Healthy Brain Ageing Program, Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia. sharon.naismith@sydney.edu.au.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Naismith
authors.affiliation: Healthy Brain Ageing Program, Brain and Mind Research Institute, University of Sydney, 94 Mallett Street, Camperdown, NSW, 2050, Australia. ian.hickie@sydney.edu.au.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hickie
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000523:psychology; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002985:Clinical Protocols; D003863:Depression / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009517:New South Wales; D011237:Predictive Value of Tests; D066244:Proton Magnetic Resonance Spectroscopy; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015525:Fatty Acids, Omega-3; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline