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

BackgroundLate-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/DesignSubjects 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.DiscussionThe 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.Trial RegistrationAustralian and New Zealand Clinical Trials Registry ACTRN12610000032055 (12 January 2010)Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0762-6) contains supplementary material, which is available to authorized users.

Prevention of Depression: A Review of Literature

“…Omega-3 a highly unsaturated fatty acid (HUFAs), number of studies was concerned with the addition of Omega-3 to the treatment regimen of already depressed patients. Which have been shown it to have beneficial effect to alleviate depressive symptoms in patients already receiving antidepressant treatment [35,83,85]. However, the evidence is not conclusive as the results of different studies are not univocal.…”

“…There are many studies which has proven that this approach is effective, feasible and acceptable to people [17,50,82]. Other studies are still in progress [83].…”

Controversies in omega-3 efficacy and novel concepts for application

“…Neuroimaging studies are also being used to help to evaluate the neurobiological effects of omega-3 in mental health. For example, a current RCT is assessing the effect of LCn3 treatment in an older age cohort on depressive symptoms and correlating these with brain changes [123].…”

The Role of Physical Exercise and Omega-3 Fatty Acids in Depressive Illness in the Elderly

“…Depressive illness in the elderly increases morbidity, disability, functional decline, caregiver burden and premature mortality, and enhances health care costs [ 2 , 6 , 9 ]. LLD represents the major risk factor for suicide in the elderly [ 10 ].…”

“…Interestingly, there is a direct link between reduction in hippocampal size and impaired mnesic functions in aged depressed patients [ 31 ]. Neuroimaging studies have demonstrated that LLD is associated with reduced gray matter volume in frontostriatal and limbic networks (including prefrontal cortex, hippocampus, amygdala, putamen, and thalamus) [ 9 , 32 ].…”