Esme Moniz-Cook

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial

BACKGROUND 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. METHODS We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimers 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 Kings College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, 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. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38. FINDINGS 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 events rated as severe (p=0·003). Five patients in every group died by week 39. INTERPRETATION 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 Alzheimers disease should be reconsidered. FUNDING UK National Institute of Health Research HTA Programme.

A European consensus on outcome measures for psychosocial intervention research in dementia care

Psychosocial intervention makes a vital contribution to dementia care. However, the lack of consensus about which outcome measures to use to evaluate effectiveness prevents meaningful comparisons between different studies and interventions. This study used an iterative collaborative, evidence-based approach to identify the best of currently available outcome measures for European psychosocial intervention research. This included consensus workshops, a web-based pan-European consultation and a systematic literature review and a rigorous evaluation against agreed criteria looking at utility across Europe, feasibility and psychometric properties. For people with dementia the measures covered the domains of quality of life, mood, global function, behaviour and daily living skills. Family carer domains included mood and burden, which incorporated coping with behaviour and quality of life. The only specific staff domain identified was morale, but this included satisfaction and coping with behaviour. In conclusion twenty-two measures across nine domains were recommended in order to improve the comparability of intervention studies in Europe. Areas were identified where improved outcome measures for psychosocial intervention research studies are required.

Study of the use of antidepressants for depression in dementia: the HTA-SADD trial--a multicentre, randomised, double-blind, placebo-controlled trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine

OBJECTIVE Depression is common in dementia, causing considerable distress and other negative impacts. Treating it is a clinical priority, but the evidence base is sparse and equivocal. This trial aimed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post randomisation compared with placebo. DESIGN Multicentre, parallel-group, double-blind placebo-controlled randomised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up. SETTING Nine English old-age psychiatry services. PARTICIPANTS A pragmatic trial. Eligibility: probable or possible Alzheimers disease (AD), depression (4+ weeks) and Cornell Scale for Depression in Dementia (CSDD) score of 8+. EXCLUSIONS clinically too critical (e.g. suicide risk); contraindication to medication; taking antidepressants; in another trial; and having no carer. INTERVENTIONS (1) Sertraline; (2) mirtazapine; and (3) placebo, all with normal care. Target doses: 150 mg of sertraline or 45 mg of mirtazapine daily. MAIN OUTCOME MEASURES OUTCOME CSDD score. Randomisation: Allocated 1 : 1 : 1 through Trials Unit, independently of trial team. Stratified block randomisation by centre, with randomly varying block sizes; computer-generated randomisation. Blinding: Double blind: medication and placebo identical for each antidepressant. Referring clinicians, research workers, participants and pharmacies were blind. Statisticians blind until analyses completed. RESULTS Numbers randomised: 326 participants randomised (111 placebo, 107 sertraline and 108 mirtazapine). OUTCOME Differences in CSDD at 13 weeks from an adjusted linear-mixed model: mean difference (95% CI) placebo-sertraline 1.17 (-0.23 to 2.78; p = 0.102); placebo-mirtazapine 0.01 (-1.37 to 1.38; p = 0.991); and mirtazapine-sertraline 1.16 (-0.27 to 2.60; p = 0.112). HARMS Placebo group had fewer adverse reactions (29/111, 26%) than sertraline (46/107, 43%) or mirtazapine (44/108, 41%; p = 0.017); 39-week mortality equal, five deaths in each group. CONCLUSIONS This is a trial with negative findings but important clinical implications. The data suggest that the antidepressants tested, given with normal care, are not clinically effective (compared with placebo) for clinically significant depression in AD. This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD. From the data generated we formulated the following recommendations for future work. (1) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia. (2) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm. (3) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life, but also the time they spend care-giving. (4) There is a need for research into alternative biological and psychological therapies for depression in dementia. These could include evaluations of new classes of antidepressants (such as venlafaxine) or antidementia medication (e.g. cholinesterase inhibitors). (5) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services. (6) Further work is needed to investigate the cost modelling results in this rich data set, investigating carer burden and possible moderators to the treatment effects. (7) There is scope for reanalysis of the primary outcome in terms of carer and participant CSDD results.

A preliminary study of the effects of early intervention with people with dementia and their families in a memory clinic

A brief individualized intervention comprising of information about diagnosis and prognosis, reinforcement of coping strategies, crisis prevention advice and memory management programmes was offered to newly diagnosed people with dementia and their families, prior to referral to the services of their local psychogeriatric community support team. The control group received diagnosis and written advice and were referred directly to their local psychogeriatric community support team. At 18-month follow-up, improvements were found in the memory scores of the experimental group. Carer wellbeing was worse in the control group and this was associated with an increased likelihood of the breakdown of home care. We suggest that psychosocial variables may be important at the time of diagnosis and note an interesting relationship between memory ability in people with dementia and carer strain. Our results can only be fully understood in the context of methodological improvements. These are outlined, for the purpose o...

Improving quality of life for people with dementia in care homes: making psychosocial interventions work.

BACKGROUND Psychosocial interventions can improve behaviour and mood in people with dementia, but it is unclear how to maximise their effectiveness or acceptability in residential settings. AIMS To understand what underlies the successful implementation of psychosocial interventions in care homes. METHOD Systematic review and meta-synthesis of qualitative research. RESULTS The synthesis of 39 qualitative papers revealed that beneficial psychosocial interventions met the needs of people with dementia to connect with others, make a meaningful contribution and reminisce. Successful implementation rested on the active engagement of staff and family and the continuing provision of tailored interventions and support. This necessitated staff time, and raised issues around priorities and risk, but ultimately helped redefine staff attitudes towards residents and the caregiving role. CONCLUSIONS The findings from the meta-synthesis can help to inform the development and evaluation of psychosocial interventions in care homes and support their widespread implementation in clinical settings.

Psychosocial interventions in dementia care research: the INTERDEM manifesto.

Dementia is a biomedical, psychological and societal disability, which poses complex challenges that are different to those of many other disabilities. As a global health problem, it takes a heavy toll on people, society and the economy. Alzheimer’s Disease International, using detailed population-based studies of the prevalence of dementia in different world regions (http://www.alz.co.uk/adi/pdf/prevalence.pdf), estimates that there are currently 30 million people with dementia worldwide, with 4.6 million new cases annually and projections for over 100 million affected people by 2050. As the population ages, the full costs will also escalate, thus making dementia an international priority. In 2008, during his term of EU presidency, French President Nicolas Sarkozy called for prioritising dementia and the development of a European-wide Alzheimer’s plan and the EU Council of Ministers has also called for collaborative action on Alzheimer’s disease research. As a follow-up to the October 2008 conference ‘The fight against Alzheimer’s disease’ organised by the French EU Presidency, and in line with the 2009 Communication from the European Commission on ‘A European initiative on Alzheimer’s disease and other dementias’, the Belgian Presidency of the EU has, from July 2010, initiated a forum to exchange best practices on societal responses to dementia. However, despite two decades of intensive research in Alzheimer’s disease and an active strategy for the recognition and monitoring of the pre-dementia stages (see Knopman et al., 2001, for the American Association of Neurology practice parameter), we are still some way away from a cure or a treatment which can prevent the disorder from worsening or significantly influence its course. Even if curative drug treatments were available, it is likely that the costs of these would be prohibitive, particularly for many developing countries at a time when the prevalence of dementia itself is set to increase in line with the escalating numbers of older people. There is a growing interest in psychosocial interventions in dementia care, but few have reached the stage of rigorous evaluation and even fewer have been widely implemented. In Europe, the diversity of languages and cultures act as an obstacle for developing, testing and implementing evidence-based psychosocial interventions. However, if psychosocial interventions have positive and costeffective outcomes on cognition and quality of life and on rates of institutionalisation, there is potential for dissemination and wider implementation through written materials or manuals detailing intervention protocols. This is particularly relevant for developing countries, where staff can be trained to deliver interventions in settings where access to the anti-dementia drugs is poor or non-existent. The need for a rapid and substantial increase in the quantity and quality of psychosocial research in dementia care has therefore never been more urgent.

Can staff training reduce behavioural problems in residential care for the elderly mentally ill

The effect of a brief in‐service training programme on the psychosocial management of behavioural disturbance in residential care is described. Although the incidence of problematic behaviour did not change 3 months after training, staff in the experimental homes reported a significant improvement in their management of problematic behaviour, as compared to the control home. However, these effects were not maintained a year later. The importance of post‐training supervision and the sociocultural context of the home in the maintenance of psychosocial intervention in residential settings is discussed.

Receiving a diagnosis of dementia: The experience over time

There are strong opinions about the advantages and disadvantages of a disclosure of dementia to the individual affected, but little is known about how they and their families understand and respond to this information. This article reports and examines the impact of receiving a diagnosis of dementia, by comparing descriptions of its impact at two weeks, with descriptions explored at 12 weeks. Interviews were undertaken on two occasions with 18 couples, one of whom had received a diagnosis of dementia, the other being a family member. The interviews revealed a gradual process of realization of what the diagnosis meant, resulting in important subtle changes in understandings of dementia and personal relationships. Disclosure of dementia occurs at one point in time, but its impact should be seen as a process. Suggestions are made on how the process of diagnosis and its sharing may enhance family partnerships and social relationships through support of both individuals with dementia and families.

Remaining hopeful in early-stage dementia: A qualitative study

Objectives: Improving the quality of life for people living with dementia is widely accepted as an important outcome in dementia care services. Positive psychology, the systematic study of strengths, capacities, and personal resources, is one framework for understanding how a person with dementia might achieve this. This study investigated the subjective experience of hope–a construct from the discipline of positive psychology in older people with early-stage dementia. Method: Ten volunteer participants over the age of 65 years were recruited from a memory clinic in England. Semi-structured interviews were used to explore participants’ hopes, in terms of their personal meaning, their resources, and the potential barriers and facilitators of hope in dementia. Interviews were analyzed using interpretative phenomenological analysis (IPA). Results: Eight themes were extracted, subsumed under two higher-order themes: ‘live in hope or die in despair’ and ‘keep living and keep living well’. Participants described how their internalized hope-fostering beliefs that were often learned during childhood were challenged by the reality of hope-hindering experiences associated with old age and dementia. A balancing process of re-appraisal enhanced resolution and this sense of stability then allowed them to develop positive attitudes towards common age-related constraints in their health and social circumstances. Conclusion: The findings offer insight into the existence, nature, and relevance of hope in the lives of people with early-stage dementia. They provide a useful framework for developing hope-fostering strategies in early interventions that aim to assist individuals with dementia to maintain their quality of life.

Systematic review of services providing information and/or advice to people with dementia and/or their caregivers

Information is a key part of service provision to people with dementia and their carers, but there is no systematic review of the evidence. This study aimed to determine whether information services confer significant benefit for quality of life, neuropsychiatric symptoms and carer burden.