Title: Vascular Augmentation of Late-life Unremitted Depression (VALUeD)
Funder: Department of Health (England)

Abstract: Background Depression occurs in about 15% of older people and is a major cause of morbidity, disability and mortality. Outcome using current therapies is very poor. Primary care studies report only a quarter remit, two-thirds remain ill and the rest develop dementia. These dismal outcomes emphasise the need to identify new treatments, including those that focus on identifiable subgroups. One such subgroup is “vascular depression”, an important target group since the presence of vascular disease strongly predicts poor depression outcomes. Two small studies have shown that a calcium channel blocker might improve treatment outcome in “vascular depression”. However, problems with study design and the use of highly selected patients mean they do not provide adequate data for planning a definitive trial. Aims Our aim is to conduct a pilot study to determine the feasibility of undertaking a large RCT (via HTA) of augmentation of standard antidepressant treatment with the calcium channel blocker amlodipine in a representative sample of older people with depression associated with vascular disease. Specifically: 1. To demonstrate using this design we can identify and recruit sufficient numbers of older people with depression from primary care. 2. To provide estimates of the efficacy of amlodipine to inform a power calculation for a definitive study. 3. To assess the tolerability and acceptability of augmentation with amlodipine in this patient group. 4. To use a qualitative sub-study to assess the validity and relevance to patients of the outcome measures used. Plan of Investigation We will recruit 80 older people from primary care with: i) unremitted “vascular depression” (defined as depressive illness after age 50 with HAM-D score of >10 despite adequate antidepressant treatment for >4 weeks; ii) A score of ?1 on the vascular scale of the CIRS-G. Exclusion criteria: on dementia, stroke or palliative care registers. Potential subjects will be identified by database searching and sent an invitation letter from their GP. They will be assessed in clinic and randomised to augmentation of their standard treatment with amlodipine or placebo for 16 weeks. Primary outcome is remission on HAM-D (?10) and secondary outcomes will include measures of function and quality of life as well as a qualitative analysis. Potential Impact The purpose of our study is to provide pilot data on trial methodology and feasibility to inform a larger scale multi-centre UK study investigating efficacy of amlodipine for “vascular depression”. A qualitative analysis will identify patient-centred outcomes for this definitive study and provide data on acceptablity. Improving remission in such a high prevalence illness will produce large quality of life gains and should lead to a substantial reduction in the excess use of services. Amlodipine is commonly prescribed in primary care, has a well established safety record and, being available generically and at low cost to the NHS, its use in reducing depression could lead to large NHS savings.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH