Summary 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 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 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 Alzheimer's disease should be reconsidered. Funding UK National Institute of Health Research HTA Programme.
Family members remain the main care providers for the increasing numbers of people with dementia, and often become depressed or anxious. In an implementation research project, we aimed to widen ...access to Strategies for RelaTives (START), a clinically and cost-effective intervention for the mental health of family carers, by laying the foundations for its implementation in the third sector. We used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to guide implementation of START, a manual-based, individually-delivered, multicomponent eight-session coping strategy intervention. We interviewed a maximum variation sample of twenty-seven stakeholders from the English Alzheimer's Society (AS), about possible difficulties in management, training, and delivery of START. We trained and supervised three AS dementia support workers in different locations, to each deliver START to three family carers. Two researchers independently coded pre-intervention interviews for themes. We assessed intervention feasibility through monitoring delivery fidelity, rating audio-recordings from 1-5 (5 being high) and interviewing facilitators, family carers and AS managers about their experiences. We assessed effectiveness on family carers' mental health using the Hospital Anxiety and Depression Scale (HADS) before and after receiving START (scores 0-42). We changed START's format by reflecting carer diversity more and increasing carer stories prominence, but core content or delivery processes were unchanged. All carers received START and attended every session. The mean fidelity score was 4.2. Mean HADS-total score reduced from baseline 18.4 (standard deviation 7.4) to follow-up 15.8 (9.7). Six (67%) carers scored as clinically depressed on baseline HADS and 2 (22%) at follow-up. Facilitators and carers rated START positively. Appropriately experienced third sector workers can be trained and supervised to deliver START and it remains effective. This has the potential for widened access at scale.
Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes.
To ...evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia.
A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods.
There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively.
In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.
Background
An unplanned hospital admission of a nursing home resident distresses the person, their family and nursing home staff, and is costly to the NHS. Improving health care in care homes, ...including early detection of residents’ health changes, may reduce hospital admissions. Previously, we identified four conditions associated with avoidable hospital admissions. We noted promising ‘within-home’ complex interventions including care pathways, knowledge and skills enhancement, and implementation support.
Objectives
Develop a complex intervention with implementation support the Better Health in Residents in Care Homes with Nursing (BHiRCH-NH) to improve early detection, assessment and treatment for the four conditions. Determine its impact on hospital admissions, test study procedures and acceptability of the intervention and implementation support, and indicate if a definitive trial was warranted.
Design
A Carer Reference Panel advised on the intervention, implementation support and study documentation, and engaged in data analysis and interpretation. In workstream 1, we developed a complex intervention to reduce rates of hospitalisation from nursing homes using mixed methods, including a rapid research review, semistructured interviews and consensus workshops. The complex intervention comprised care pathways, approaches to enhance staff knowledge and skills, implementation support and clarity regarding the role of family carers. In workstream 2, we tested the complex intervention and implementation support via two work packages. In work package 1, we conducted a feasibility study of the intervention, implementation support and study procedures in two nursing homes and refined the complex intervention to comprise the Stop and Watch Early Warning Tool (S&W), condition-specific care pathways and a structured framework for nurses to communicate with primary care. The final implementation support included identifying two Practice Development Champions (PDCs) in each intervention home, and supporting them with a training workshop, practice development support group, monthly coaching calls, handbooks and web-based resources. In work package 2, we undertook a cluster randomised controlled trial to pilot test the complex intervention for acceptability and a preliminary estimate of effect.
Setting
Fourteen nursing homes allocated to intervention and implementation support (
n
= 7) or treatment as usual (
n
= 7).
Participants
We recruited sufficient numbers of nursing homes (
n
= 14), staff (
n
= 148), family carers (
n
= 95) and residents (
n
= 245). Two nursing homes withdrew prior to the intervention starting.
Intervention
This ran from February to July 2018.
Data sources
Individual-level data on nursing home residents, their family carers and staff; system-level data using nursing home records; and process-level data comprising how the intervention was implemented. Data were collected on recruitment rates, consent and the numbers of family carers who wished to be involved in the residents’ care. Completeness of outcome measures and data collection and the return rate of questionnaires were assessed.
Results
The pilot trial showed no effects on hospitalisations or secondary outcomes. No home implemented the intervention tools as expected. Most staff endorsed the importance of early detection, assessment and treatment. Many reported that they ‘were already doing it’, using an early-warning tool; a detailed nursing assessment; or the situation, background, assessment, recommendation communication protocol. Three homes never used the S&W and four never used care pathways. Only 16 S&W forms and eight care pathways were completed. Care records revealed little use of the intervention principles. PDCs from five of six intervention homes attended the training workshop, following which they had variable engagement with implementation support. Progression criteria regarding recruitment and data collection were met: 70% of homes were retained, the proportion of missing data was < 20% and 80% of individual-level data were collected. Necessary rates of data collection, documentation completion and return over the 6-month study period were achieved. However, intervention tools were not fully adopted, suggesting they would not be sustainable outside the trial. Few hospitalisations for the four conditions suggest it an unsuitable primary outcome measure. Key cost components were estimated.
Limitations
The study homes may already have had effective approaches to early detection, assessment and treatment for acute health changes; consistent with government policy emphasising the need for enhanced health care in homes. Alternatively, the implementation support may not have been sufficiently potent.
Conclusion
A definitive trial is feasible, but the intervention is unlikely to be effective. Participant recruitment, retention, data collection and engagement with family carers can guide subsequent studies, including service evaluation and quality improvement methodologies.
Future work
Intervention research should be conducted in homes which need to enhance early detection, assessment and treatment. Interventions to reduce avoidable hospital admissions may be beneficial in residential care homes, as they are not required to employ nurses.
Trial registration
Current Controlled Trials ISRCTN74109734 and ISRCTN86811077.
Funding
This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in
Programme Grants for Applied Research
; Vol. 9, No. 2. See the NIHR Journals Library website for further project information.
Abstract Recent approvals of amyloid immunotherapy drugs for early Alzheimer's disease (AD) have been highly controversial. In this piece, we consider challenges from the clinical, population health, ...and health systems perspectives to the role that the new AD drugs might be expected to play, now and in the future, in alleviating the morbidity caused by AD in the population. Clinically, short‐term effects are small, adverse events are frequent, treatment regimens are burdensome, and, crucially, long‐term effects are unknown. At a population level, there is always likely to be a trade‐off between breadth of access and magnitude of benefit for any given individual. At a health system level, roll out of treatment even for only narrowly‐defined patient groups will involve considerable resources to identify and treat eligible patients, with profound opportunity costs. Our considered view on current evidence is that there are challenges from each perspective to imagining a foreseeable future in which amyloid immunotherapy significantly alleviates AD morbidity at scale. Highlights Recent approvals of Alzheimer's drugs have met with excitement but also controversy. Trial effects are small, adverse effects concerning, and long‐term effects unknown. Results from trial cohorts may not generalize to broader, more complex patients. Significant resource requirements of eligibility assessment and drug administration. Use in “presymptomatic” populations is not supported by current evidence.
Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is ...a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia.
This parallel-group, double-blind, placebo-controlled trial—the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)—was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897.
Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference –1·74, 95% CI –7·17 to 3·69; p=0·53). The number of controls with adverse events (65 64% of 102 controls) was similar to that in the mirtazapine group (67 66% of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065).
This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia.
UK National Institute for Health Research Health Technology Assessment Programme.
Family members remain the main care providers for the increasing numbers of people with dementia, and often become depressed or anxious. In an implementation research project, we aimed to widen ...access to Strategies for RelaTives (START), a clinically and cost-effective intervention for the mental health of family carers, by laying the foundations for its implementation in the third sector. We used the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to guide implementation of START, a manual-based, individually-delivered, multicomponent eight-session coping strategy intervention. We interviewed a maximum variation sample of twenty-seven stakeholders from the English Alzheimer's Society (AS), about possible difficulties in management, training, and delivery of START. We trained and supervised three AS dementia support workers in different locations, to each deliver START to three family carers. Two researchers independently coded pre-intervention interviews for themes. We assessed intervention feasibility through monitoring delivery fidelity, rating audio-recordings from 1-5 (5 being high) and interviewing facilitators, family carers and AS managers about their experiences. We assessed effectiveness on family carers' mental health using the Hospital Anxiety and Depression Scale (HADS) before and after receiving START (scores 0-42). We changed START's format by reflecting carer diversity more and increasing carer stories prominence, but core content or delivery processes were unchanged. All carers received START and attended every session. The mean fidelity score was 4.2. Mean HADS-total score reduced from baseline 18.4 (standard deviation 7.4) to follow-up 15.8 (9.7). Six (67%) carers scored as clinically depressed on baseline HADS and 2 (22%) at follow-up. Facilitators and carers rated START positively. Appropriately experienced third sector workers can be trained and supervised to deliver START and it remains effective. This has the potential for widened access at scale.
Background:
Despite media and academic interest on assisted dying in dementia, little is known of the views of those directly affected.
Aim:
This study explored the views of former carers on assisted ...dying in dementia.
Design:
This was a qualitative study using thematic analysis.
Setting/participants:
A total of 16 former carers of people with dementia were recruited through national dementia charities and participated in semi-structured interviews.
Results:
While many supported the individual’s right to die, the complexity of assisted dying in dementia was emphasized. Existential, physical, psychological and psychosocial aspects of suffering were identified as potential reasons to desire an assisted death. Most believed it would help to talk with a trained health professional if contemplating an assisted death.
Conclusion:
Health workers should be mindful of the holistic experience of dementia at the end of life. The psychological and existential aspects of suffering should be addressed, as well as relief of physical pain. Further research is required.
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