Beyond ageing: A randomised controlled trial of folic acid and vitamin B12, physical activity, mental health literacy for the indicated prevention of depression
Dr Janine Walker
Professor Helen Christensen
Australian National University
Beyond Blue grant
Project completion year
The Beyond Ageing Project
Depression in later life is common with 3.6 per cent to 4.8 per cent of people under 60 years reporting 12-month major depression, while 8 per cent to 37.4 per cent report with significant depressive symptoms. Late-life depression may result in impaired cognitive, physical and social functioning, and predispose to suicide. In the USA in 2000, for the overall population, a cost of over $83 billion was incurred, with $23 billion in direct medical costs and $51 billion due to workplace costs and lost productivity. The prevalence of depressive disorders is projected to double from its present level by 2050.
If the adverse impact of depression is to be minimised, there is a clear need to develop effective, economical, and accessible prevention strategies. Ideally, these should also build upon the community’s preference for lifestyle and psychological interventions. The first step is to identify those interventions that reduce depressive symptoms in a community-based cohort that reports subsyndromal depressive disorders. If successful, such interventions can then constitute the basis for larger indicated prevention trials. However, to date, the development and evaluation of such programs has been minimal.
The Beyond Ageing Research Project is a randomised control trial study involving almost 1,000 older people at risk of developing major depression. This large research project on depression and the elderly is examining a range of treatments for this target group, including vitamin supplements, exercise and improving knowledge of depression. By late 2008, the research had produced the following noteworthy findings:
- Mental health literacy was found to be effective in reducing depressive symptoms at the six-week and 12-month follow-up time-frames. This was considered to be a significant impact when compared to the control group who had received pain and arthritis management information.
- Participants who received folate and vitamin B12 had stable homocysteine levels while participants who received placebo tablets had elevations in homocysteine, a known risk factor for cardiovascular disease.
In late 2008, additional investment support was provided by Beyond Blue to enable the project to continue for a further two years. This enabled follow-up assessments to be undertaken and analysis of whether the benefits associated with the interventions persist beyond 12 months.
Follow up study findings
In the follow up study of symptomatic older community-dwelling participants, all trial and control interventions reduced depressive symptoms over the course of the intervention and the post-intervention follow-up time points. Only those who received mental health literature materials experienced a significant decrease in depressive symptoms at six weeks relative to the control condition. This finding replicates earlier trials where web-based depression literacy materials supported by weekly telephone tracking calls reduced depressive symptoms1 in community samples.
Importantly, however, the study found no specific additional effect of folic acid + B12 supplementation on reduction of depressive symptoms. This was unlikely to be due to adherence issues given the biochemical analyses showing increased levels of folate. This finding does not preclude an effect at higher doses than used in this trial. No dose-response studies have been reported previously, and there is poor understanding of the duration of treatment necessary to produce an effect.2-4 Randomised controlled trials have investigated a range of folate doses from 200 to 5,000 mcg/day with varying findings.3-4 Folic acid and vitamin B12 are unlikely to be an effective short-term intervention for preventing depression in doses that can be recommended as a dietary supplement. The study replicates the null effect from an earlier, smaller and thus underpowered trial.2 It is possible that such interventions need to be delivered over a longer period to reduce vascular and other metabolic risk factors to depression.5-7
- Christensen H, Griffiths KM, Jorm AF. Delivering interventions for depression by using the internet: randomised controlled trial. British Medical Journal 2004;328(7434):265-68A.
- Ford A, Flicker L, Thomas J, Norman P, Jamrozik K, Almeida O. Vitamins B(12), B(6), and Folic Acid for Onset of Depressive Symptoms in Older Men: Results From a 2-Year Placebo-Controlled Randomized Trial. Journal of Clinical Psychiatry 2008:e1-e7.
- Reynolds EH. Folic acid, ageing, depression, and dementia. British Medical Journal 2002;324(2002 Jun 22):1512-15.
- Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. Journal of Psychopharmacology 2004;18(2):251-56.
- Hickie I, Naismith S, Ward PB, Scott E, Mitchell P, Wilhelm K, et al. Vascular risk and low serum B12 predict white matter lesions in patients with major depression. Journal of Affective Disorders 2005;85(3):327-32.
- Hickie I, Scott E. Late-onset depressive disorders – a preventable variant of cerebrovascular disease. Psychological Medicine 1998;28(5):1007-13.
- Hickie I, Scott E, Naismith S, Ward PB, Turner K, Parker G, et al. Late-onset depression: genetic, vascular and clinical contributions. Psychological Medicine 2001;31(8):1403-12.
Jenkins A, Christensen H, Walker JG & Dear KBG. (In press) The Effectiveness of Distance Interventions for Increasing Physical Activity: A Review. American Journal of Health Promotion. Accepted 07/2008
Busby Grant JA, Mackinnon AJ, Christensen H & Walker JG. (revision). Participants' perceptions of motivation, randomisation and withdrawal in a community-based prevention randomised controlled trial, Social Science & Medicine.
Walker JG, Mackinnon AJ, Batterham P, Jorm AF, Hickie I, McCarthy A, Fenech M & Christensen H. (Submitted). The Beyond Ageing Project: A randomized controlled trial of folic acid and vitamin B12, physical activity, and mental health literacy for the indicated prevention of depression. JAMA.
Invited articles – non-refereed
Walker JG. (2006). Is physical activity an effective treatment for depression? PARCupdate. Primary Mental Health Care Australian Resource Centre: Adelaide, Australia; 16-17.
Walker JG. (2005). Practical ways for older people to prevent depression: The Beyond Ageing Project. Quest, 4, 12-15.
Tayler G, Griffiths K & Christensen H. (2007). Interpersonal psychotherapy: A “how to” guide for tackling relationships and improving wellbeing. Centre for Mental Health Research: Canberra, Australia.
Banfield M & Griffiths K. (2006). Sleep well: A “how to” guide for improving sleep. Centre for Mental Health Research: Canberra, Australia.
Christensen H & Tayler G. (2006). What works for anxiety. Centre for Mental Health Research: Canberra, Australia.
Jenkins A & Walker JG. (2006). Structured problem solving training: Practical ways to manage depression. Centre for Mental Health Research: Canberra, Australia.
Frazer C, Christensen H, Griffiths K, Walker JG & Jenkins A. (2005). Help for depression: What works for older people. Centre for Mental Health Research: Canberra, Australia.
Walker JG & Jenkins A. (2005). Over the hill: A handbook for making physical activity a part of your life. Centre for Mental Health Research: Canberra, Australia.