Authors' objectives: BACKGROUND Dementia causes irreversible decline in intellectual, social and physical functioning with 800,000 people affected and costs of over £20billion pa in the UK. In 30 years numbers will double and costs triple. Impacts on patients and carers are devastating so improving dementia care is now a national policy priority. Behavioural and psychological symptoms in dementia (BPSD eg agitation, aggression, wandering, shouting, repeated questioning and sleep disturbance) are common occurring in up to 90% of cases. Agitation, defined as inappropriate verbal, vocal or motor activity which is not an outcome of need and encompasses physical and verbal aggression, is particularly problematic affecting nearly 50% of people with AD over a month. 80% with clinically significant symptoms have them six months later. Agitation is associated with deteriorating relationships with family and professional carers, institutionalisation, increased costs of care, distress and decreased quality of life. Antipsychotics, the mainstay of drug treatment for agitation in AD, do harm. A ministerial enquiry identified that a third of people with dementia receive these drugs and they cause 1,800 deaths pa in the UK. Reduction in antipsychotic use in dementia is therefore a government priority and research into safe effective alternatives is a government research priority. INTERVENTION Emerging evidence suggests two inexpensive, safe, routinely used drugs (mirtazapine, an antidepressant; carbamazepine, an anticonvulsant) may be effective in treating agitation in dementia. We propose to determine if either decreases agitation in dementia. We will carry out a trial of the effect on agitated behaviours at 6 and 12 weeks of mirtazapine or carbamazepine compared to inactive dummy capsules (placebo) and long term effects of the 12 weeks randomised treatment at 26 and 52 weeks. We will recruit 470 cases from 8 centres (59 from each); they will be allocated randomly on a 1:1:1 basis to receive either mirtazapine, carbamazepine or placebo, all with usual care. The medication will be prepared so neither researchers nor participants are aware of which they receive. SITES 8 mental health services in England. OUTCOMES Our main outcome is agitation in dementia measured by the Cohen Mansfield Agitation Inventory[13] (CMAI the best validated/most widely used measure of agitation in dementia). We will also see if the medications affect: quality of life, cognitive impairment, carers, and cost. These will be measured at baseline, 6&12w. Long term outcomes (CMAI, treatment status, institutionalisation and death) will be assessed by telephone interviews at 26&52w. ETHICAL ISSUES We have extensive experience of working with people with dementia, their carers and health providers. We will recruit people across severity of dementia; some may not have the capacity to give informed written consent. For them we will ask carers for assent; the person with dementia would only be enrolled if they showed no dissent. We will work with the Alzheimer s Society and PPI to ensure best ethical practice. All participants will have had a trial of non-drug treatment, as set out in the DH/AS algorithm, prior to entering the trial. TEAM A broad and experienced multidisciplinary team experienced in dementia, clinical trials in dementia, statistics, health economics, implementation, policy and service user/carer perspectives.

Project Status: Ongoing

URL for project: http://www.nets.nihr.ac.uk/projects/hta/1311576

Anticipated Publish Date: 2021

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

Copyright: Queen's Printer and Controller of HMSO