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Brighton & Sussex Medical School

Randomised controlled trials in dementia

BSMS > Research > Neuroscience > Centre for Dementia Studies > Research > Randomised controlled trials in dementia

Randomised controlled trials in dementia

Randomised controlled trials (RCT) in dementia generate the strongest evidence possible for clinical behaviour change.

CDS works with industry and with investigator-led research in developing and testing new treatments for AD and other dementias as well as the treatment of co-morbidities, such as depression in dementia. The CDS has carried out more than 35 clinical trials in dementia working with national colleagues and multinational pharmaceutical companies.


Study of mirtazapine or carbamazepine for agitation in dementia: HTA-SYMBAD

A pragmatic, multi centre, double-blind, placebo controlled randomised controlled trial to assess the clinical and cost effectiveness of mirtazapine or carbamazepine against placebo (all with usual care) at 6 and 12 weeks, and limited assessment of longer term outcomes at 26 and 52 weeks, in patients with Alzheimer’s Disease (AD) and agitated behaviours which have not responded to standardised non-drug treatment.


Funded by: NIHR HTA
PI: Dr Naji Tabet
CI: Prof Sube Banerjee
Status: In progress


HTA-SADD trial of antidepressants for depression in dementia


Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo.


We undertook a parallel-group, double-blind, placebo-controlled trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimer’s disease, depression (lasting ≥4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at King’s College London (UK) randomly allocated participants in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre.


Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1.17, 95% CI –0.23 to 2.58; p=0.10) or mirtazapine (0.01, –1.37 to 1.38; p=0.99), or between participants in the mirtazapine and sertraline groups (1.16, –0.25 to 2.57; p=0.11); these findings persisted to 39 weeks. Fewer controls had adverse reactions (29 of 111 [26%]) than did participants in the sertraline group (46 of 107, 43%; p=0.010) or mirtazapine group (44 of 108, 41%; p=0.031), and fewer serious adverse eventsrated as severe (p=0.003). Five patients in each group died by week 39.


Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer’s disease should be reconsidered.

Funded by: NIHR HTA
CI: Prof Sube Banerjee
Status: Completed