Study of Mirtazapine or Carbamazepine for Agitation in Dementia

  • Research type

    Research Study

  • Full title

    A pragmatic, multi-centre, double-blind, placebo controlled randomised trial to assess the safety, clinical and cost effectiveness of mirtazapine or carbamazepine in patients with Alzheimer's Disease (AD) and agitated behaviours.

  • IRAS ID

    187026

  • Contact name

    Sube Banerjee

  • Contact email

    s.banerjee@bsms.ac.uk

  • Sponsor organisation

    University of Sussex

  • Eudract number

    2015-003410-25

  • Duration of Study in the UK

    3 years, 2 months, 28 days

  • Research summary

    Research Summary

    This study is designed to establish the best treatment for the management of agitation and/or aggression in people with dementia. Agitation and aggression are common in people who suffer from dementia and can cause problems for the patients, families and the people caring for them. There are medicines available to treat agitation, but it is not clear which treatments work best for people with dementia. This study will compare 2 medicines with a placebo (a tablet designed to look like a medicine but that has no active component) to see if either are suitable for treating agitation in dementia. The study is divided into 3 parts: the consent and assessment part is likely take a few weeks; the treatment part will take 12 weeks; and the follow up part will continue to 12 months after treatment starts. Patients will be consented alongside a family or paid carer who is willing and able to consent to provide information for the study and to help the patient take the medication they will be given. Patients will continue to receive care from their doctors and other health and social services in the usual way whilst they are in the trial. The patient will be asked to take 1 tablet for the first 2 weeks of treatment in the trial, 2 tablets in the next 2 weeks and 3 tablets for the remaining 12 week treatment period (unless there are concerns about side effects resulting from them taking the medication). The patient, their carer, their doctors and the research workers will not know whether the patient is taking either of the active medications or the placebo until the end of the trial, although it is possible to find out which medicine they are taking in the event of a medical emergency.

    Summary of Results

    This is a trial with negative findings but important clinical implications. The data suggests that mirtazapine is not clinically effective (compared to placebo) for clinically significant agitation in dementia. Our findings suggest that there is little reason to recommend the use of mirtazapine for people with dementia who experience agitation. Effective and cost-effective management strategies for agitation in dementia are needed, particularly where non-pharmacological approaches have been unsuccessful, and for people with dementia and their carers living in community settings.

    241 participants were recruited and randomised (102 mirtazapine, 102 placebo and 40 carbamazepine) The carbamazepine arm was discontinued in August 2018 due to slow recruitment and the carbamazepine versus placebo analyses were therefore statistically underpowered.
    The primary outcome was change in Cohen Mansfield Agitation Inventory (CMAI) at 12 weeks. Mean scores at 12 weeks were not significantly different between participants receiving mirtazapine and placebo (-1.74, 95% CI -7.17 to 3.69, p=0.53). The number of placebo participants with adverse events (65/102 [64%]) was similar to that in the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the placebo group (n=1), with post-hoc analysis suggesting this was of marginal statistical significance (p=0.065) and this mortality difference did not persist at 6- and 12-month assessment.
    Severity of agitation decreased in both groups at 6 weeks by around 10 CMAI points and continued to be lower than baseline scores at 12 weeks. This change between baseline and 6-week and 12-week outcomes is shown by the separation in 95% confidence limits. At no point was the CMAI difference between the groups statistically significant.

    In this study, there were clear decreases in agitation scores overall, with a clinically and statistically significant 10-point drop in the first 6 weeks of treatment, which was then maintained from 6 to 12 weeks; however, this drop was not attributable to mirtazapine because it was also seen in the placebo group. This suggests many cases of agitation will resolve with usual care and without the need for medication.

  • REC name

    South Central - Hampshire A Research Ethics Committee

  • REC reference

    15/SC/0606

  • Date of REC Opinion

    4 Nov 2015

  • REC opinion

    Further Information Favourable Opinion