Randomised trial of Blood pressure Rapid Intensive Lowering And Normal Treatment for Mood and Cognition in Persistent Depression (BRILiANT Mood Study)

Lead Research Organisation: Newcastle University
Department Name: Institute for Ageing and Health


Depression is a very common illness in people of all ages and many people with severe (clinically relevant) depression (called major depression) remain unwell after standard treatments with antidepressant drugs and talking therapies. The persistence of key symptoms of depression in these people makes it very difficult for them to function normally in their daily lives at work or at home and consequently contributes a lot to the high cost of looking after people with depression. Two types of persistent symptom are those related to mood (such as reduced ability to enjoy oneself) and those related to memory ('memory problems' such as forgetting things and difficulty in reasoning). There is therefore a great need to find new types of treatment. Since depression seems to be an illness with different causes and patterns of symptoms then it seems unlikely that a single new treatment will help everyone. A different approach is to find subgroups of people who seem to share the same cause of their illness. One such subgroup is people with high blood pressure (hypertension) since there is evidence that hypertension causes changes in the brain which may be an important cause of persisting symptoms in middle-aged and older people with major depression. Poorly treated hypertension is common since about a half of middle aged and older people have hypertension and half of these are not properly treated. Such hypertension changes the blood vessels which supply the brain and makes them more likely to fail to adequately supply the blood the brain needs. This is thought to cause parts of the brain not to function normally and lead to the persistent symptoms of depression and the disability this produces. Previous research shows that treating hypertension much more rapidly (over a few weeks) and with more drugs than usual can be done safely and leads not only to better control of blood pressure but to improved bloodflow in the brain. This is called rapid intensive BP lowering. The increase in bloodflow in the brain with this treatment might allow improvement of these persistent symptoms so people get completely well from their depression. However, this intensive BP lowering treatment has not been tried before in depression and so we don't know if doing this will help treat depression. We therefore propose to test this by comparing those who have normal treatment for their hypertension with people receiving the intensive BP lowering regime. We will recruit 60 people who have persistent symptoms of major depression and hypertension that needs better treatment. We will recruit people aged 50 to 80 because such hypertension is more common in this age group (about a quarter of such older adults have inadequately treated hypertension). These people will be randomly allocated to a standard hypertension treatment group (following NICE recommendations) or intensive hypertension treatment group. They will be seen regularly by a study doctor who will monitor their BP, check for any side-effects and alter their treatment depending on which treatment group they are in. Before beginning treatment and at the end of the 12 week study period different research staff, who do not know which treatment patients are receiving, will ask questions to rate patients' mood and 'memory symptoms' to compare the effects of intensive BP lowering with the standard hypertension treatment. They will also have a special brain scan to measure bloodflow in the brain before treatment and after 12 weeks and the scientist rating this again will not know which treatment they have had. We have chosen 12 weeks because studies of depression treatments usually allow 6 weeks to look for benefits and we know it takes 6 weeks to have a significant improvement in bloodflow in the brain with the rapid intensive BP lowering treatment.

Technical Summary

Currently even with optimum treatment a large proportion of people with major depression do not attain remission. There is therefore a pressing need to examine alternative approaches by identifying subgroups with shared features. One such subgroup is middle-aged and older adults with poorly controlled hypertension, about a quarter of this age-group. Persistent mood and cognitive symptoms are strongly related to cerebrovascular disease due to hypertension. Mechanistically, poorly treated hypertension has adverse effects on cerebral autoregulation, making the brain more vulnerable to inadequate perfusion. Previous work showed lowering blood pressure (BP) can correct these changes and improve cerebral perfusion. We propose to test the novel hypothesis that intensive BP lowering improves mood and cognitive symptoms in this subgroup and does so by improving cerebral bloodflow. We will recruit 60 subjects with persistent symptoms (Hamilton depression rating (HAM-D) >10) after treatment of major depression who also have inadequately treated hypertension. We will use a PROBE (prospective randomised open blinded end-point) design, with subjects randomised to standard BP treatment (NICE recommended) or protocolised intensive BP lowering. We have demonstrated this produces a 10mm Hg group difference with cerebral bloodflow improvements in the intensive group by 6 weeks. Outcome measures, assessed blind to treatment at 12 weeks: mood change with HAM-D; neuropsychological functioning (memory and executive function); cerebral blood flow using MRI arterial spin labelling. Due to the inherent problem in trials utilising executive functioning as an outcome (i.e. how to deal with the complexity of this neuropsychological domain in terms of its multiple processes) we will explore deriving a small number of composite measures that reflect executive functions and memory. We will use the data from this study to adequately power a further study which we will submit to the MRC DCS scheme.

Planned Impact

The pilot and experimental nature of this call and application mean the immediate impact will be on providing evidence to inform and power the design of further studies, e.g. through the MRC DCS scheme. If we obtain further evidence from such studies that intensive BP lowering has important benefits on mood and cognition for people with depression and co-morbid hypertension then the impact would be much wider but not for several years until such further studies were completed.

At this stage such evidence would have important implications for the large number of people with depression and poorly treated hypertension since depression is common and inadequately treated hypertension is also common. Although at that stage the immediate beneficiaries would be people with depression who have not responded fully to first line treatment in primary care and secondary care psychiatry services, the impact would extend much further. Large numbers of people with hypertension and cerebrovascular disease might also benefit since depressive symptoms and cognitive impairment are very common in such people as well. If our hypothesis is correct that the mechanism of benefit involves improving cerebral bloodflow then utilising this BP lowering intervention might also have an important preventive role in reducing the longer term burden of mood and cognitive symptoms induced by cerebrovascular disease; that is, the morbidity from chronic depression might be ameliorated by a treatment improving a fundamental abnormality.

Furthermore, the impact would extend to health service policy makers and managers developing such services because management of blood pressure is not currently part of routine assessment or management of people with depression in primary care or secondary care services. Thus there would be an important need to ensure such people are informed and educated about this new therapeutic approach in depression and we have outlined how we would achieve this in our Communications Plan.

The impact of such findings would also include those in relevant charities, such as MIND and the British Hypertension Society (BHS). Such bodies are important in shaping future healthcare policy and in liaising with the public. Our Communications Plan states how we would inform such charities about our findings and we would also work with them locally and nationally to develop updated guidance and information sheets.
Description Northern Region Old Age Psychiatry Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Research presentation on rationale for using BP treatments to help with depression

Increased engagement with consultants in regional NHS services
Year(s) Of Engagement Activity 2012
Description Regional 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact GPs and research nurses asked about our research and took information

Some practitioners later approached us with patients for our study
Year(s) Of Engagement Activity 2012,2013