NIHRDataInsights/HRCSData huggingface dataset:
Title: A practical randomised controlled double-blind trial of antipsychotic treatment of very late-onset schizophrenia-like psychosis: The ATLAS Trial
Funder: Department of Health (England)

Abstract: Very late-onset schizophrenia-like psychosis is a common condition which affects an estimated 34000 of the UK population aged over 60 and with 2800 new service contacts each year. After dementia and depression these patients represent the largest diagnostic group presenting to Old Age Psychiatry services. Impairments in quality of life associated with psychosis are severe and comparable to those seen in younger schizophrenia patients and elderly people with dementia. Patients often suffer the effects of their delusional beliefs for 10 or 20 years and this has a negative impact upon their families neighbours and local social and housing services. Antipsychotic drugs are widely used to treat late-onset schizophrenia-like psychosis patients but the balance of benefits and risks of this approach have not been properly evaluated. A Cochrane review concludes that there is no reliable clinical trial evidence upon which to base treatment guidelines. Antipsychotic drugs may increase the risk of stroke and death. This risk needs to be balanced against potential benefits of such treatment which cannot currently be quantified without clinical trial evaluation. A large randomised trial is urgently needed to assess reliably the value of antipsychotic drugs in late-onset schizophrenia-like psychosis. ATLAS is a double-blind placebo-controlled trial in patients with very late-onset schizophrenia-like psychosis to evaluate whether giving 12 weeks treatment with a low dose of the antipsychotic drug amisulpride produces sufficient benefit to outweigh the potential risks. ATLAS also evaluates whether prolonging treatment for a further 24 weeks among patients who have already been treated with amisulpride for 12 weeks confers additional benefit. The primary outcome measures are change in the Brief Psychiatric Rating Scale (BPRS) score and the proportions who discontinue treatment because of a perceived lack of efficacy. ATLAS will also assess side-effects safety the effects of treatment on quality of life and the cost-effectiveness of amisulpride treatment. As well as evaluating therapeutic approaches ATLAS provides a unique opportunity to obtain a better understanding of the risk factors and natural history of late-onset schizophrenia-like psychosis and to identify patient characteristics predictive of response to antipsychotic therapy.ATLAS aims to randomise 300 patients in a 2:1 ratio between 12 weeks of amisulpride and matching placebo. Patients allocated placebo will then switch to amisulpride whereas those receiving amisulpride will be randomised to continuing with either amisulpride or placebo. Thus all patients receive some active treatment. To make widespread participation feasible trial procedures and documentation are kept to a minimum.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Obsessive Compulsive Treatment Efficacy Trial (OCTET)
Funder: Department of Health (England)

Abstract: Obsessive compulsive disorder (OCD) is a common problem affecting 13% of the population. OCD makes people anxious and unhappy interferes with everyday activities such as working or looking after relatives and it costs patients their families and the country a lot of money. OCD rarely improves without treatment. New treatment guidelines were developed by experts in 2005. These guidelines recommend that people with OCD receive a form of psychological help or talking treatment called cognitive behavioural therapy (CBT). The guidelines suggest that this CBT might be delivered as a self help approach. In self helpCBT is delivered through a book or computer programme with some guidance from a mental health professional. Guidance can be delivered over the telephone by email or facetoface. However we still do not know which method of self helpis most useful or how useful they are compared to those on a waiting list for CBT. Our proposed study will test 2 different self help treatments for OCD. These are 1) computerised CBT (cCBT) using an internet delivered OCD treatment package called OCFighter with email or telephone support from a mental health professional; and 2) a self help book which helps people to use CBT combined with facetoface telephone or email support from a mental health professional. This treatment is called guided self help. Both treatments will be delivered over a 12 week period. We want to see if the new treatments (cCBT and guided self help) are effective in the short and longer term. Our study will also find out how satisfied people are with the treatments and which they prefer. Finally we will calculate the costs of each treatment to OCD sufferers their families and the NHS.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: Focusing On Clozapine Unresponsive Symptoms (FOCUS): a randomised controlled trial
Funder: Department of Health (England)

Abstract: We will test the hypotheses that:1. In people with a diagnosis of a schizophrenia spectrum disorder who have an inadequate response to or are unable to tolerate clozapine Cognitive Behavioural Therapy (CBT) plus Treatment As Usual (TAU) will lead to improvement in psychotic symptoms measured using a psychiatric interview (PANSS) over a 21-month follow-up period compared with TAU alone2. CBT plus TAU will lead to improved quality of life and user-defined recovery compared to TAU alone3. CBT plus TAU will lead to a reduction in affective symptoms and negative symptoms compared to TAU alone 4. CBT plus TAU will be cost effective compared to TAU alone5. It will be possible to develop a risk model that identifies baseline factors that predict good outcome to CBTBackground and aim: Clozapine is the only antipsychotic with convincing evidence for efficacy in strictly defined treatment resistant schizophrenia. But even in this category clozapine has limited efficacy with 30-40% showing an inadequate response to the drug. There is some evidence that cognitive behavioural therapy (CBT) can sometimes produce more improvement however the evidence is limited. This study plans to evaluate the possible benefits of CBT added to clozapine for 9 months with people with psychosis whose symptoms are considered treatment resistant to clozapine.Method: A parallel group randomised outcome blind evaluation (PROBE) trial comparing the addition of standardised CBT intervention to treatment as usual for people with psychosis who are unable to tolerate or have an inadequate response to clozapine. A total of 485 participants aged between 16 and 65 with a diagnosis on the schizophrenia spectrum or who meet criteria for early intervention in psychosis and who experience persistent symptoms despite an adequate trial of clozapine monotherapy will be recruited from five sites in the UK (Southampton Manchester Newcastle Edinburgh and Glasgow).Analysis: The main analyses will be based on the Intention-to-Treat principle. The primary outcome measure the Positive and Negative Syndrome Scale (PANSS) will be analysed using a linear model that adjusts for pre-specified baseline covariates strongly associated with outcome. Secondary outcomes will be analysed with general linear models and the development of treatment effects over time will be analysed using repeated measures models. The influence of compliance will be addressed via causal or mediation models.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: The clinical and cost effectiveness of lamotrigine for people with borderline personality disorder: Randomised controlled trial
Funder: Department of Health (England)

Abstract: Background:People with Borderline Personality Disorder (BPD) experience affective instability recurrent suicidal behaviour and poor interpersonal functioning. No drugs are currently licensed for the treatment of BPD but small-scale studies of mood stabilisers such as lamotrigine suggest that they may have a role in improving the mental health of people with this disorder.Aims:To examine the clinical and cost-effectiveness of adding lamotrigine to usual care for people with borderline personality disorder. To achieve this aim we will:i. Test whether adding lamotrigine improves mental health over a 52 week period in comparison to a placebo control. ii. Examine whether the addition of lamotrigine to usual care for adults with BPD improves social functioning and health-related quality of life reduces the incidence of suicidal behaviour and lowers the amount of antipsychotic and other psychotropic medication that people are prescribed.iii. Compare the incidence of side effects among those prescribed lamotrigine in addition to usual care in comparison to a placebo control. iv. Examine the cost cost-utility and cost-effectiveness of adding lamotrigine to usual in comparison to a placebo control. Methods:A multi-centre two-arm parallel group double-blind placebo-controlled randomised trial. Equal numbers of eligible patients will be randomised to receive lamotrigine or placebo in addition to their usual care. We aim to recruit 252 people aged 18 or over and follow up 85% one year later. Our primary outcome measure is symptoms of borderline personality disorder measured at 52 weeks. Our secondary outcomes are depression incidence and severity of suicidal behaviour social functioning health-related quality of life assessed side effects of study treatments and resource use.Primary statistical analysis will be performed on an intention to treat basis.


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS;6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults
Funder: Department of Health (England)

Abstract: BackgroundAlthough several treatment options (psychological or pharmacological) are available for obsessive compulsive disorder it is largely unknown whether clinically important differences exist between them ObjectivesWe will aim to determine the clinical effectiveness acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of Obsessive Compulsive Disorder using both direct and indirect evidence in a Bayesian framework.Search MethodsWe will review the Cochrane collaboration depression anxiety and neurosis review group controlled trials registers. References to trials for inclusion in the Group’s registers are collated from routine generic searches of all major databases. All electronic searches will be supplemented by hand-searchSelection CriteriaWe will include double-blind randomized controlled trials comparing at least one active antidepressant with another active antidepressant or placebo as oral monotherapy in the treatment of OCD. We will also include randomized controlled trials comparing a behavioural or cognitive behavioural intervention to a matched control treatment or to each other (BT vs CBT). Studies that used non-blinded outcome raters will not be excluded but we will carry out a sensitivity analysis. Data Collection and AnalysisTwo reviewers will conduct study selection data extraction and methodological quality assessment independently. We will perform a multiple treatments meta-analysis (MTM). We will perform MTM with a Bayesian framework in order to estimate the probability for each intervention to be the best for each positive outcome given the results of the MTM. The analysis will be performed using WinBUGS. For the economic synthesis we will develop a probabilistic model of alternative treatments in order to evaluate the relative cost-effectiveness of these treatments DiscussionThe results could help inform national evidence-based guidelines to determine the most appropriate treatment for OCD. Through NICE these guidelines will be disseminated extensively through the NHS.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: COBRA (Cost and Outcome of BehaviouRal Activation): a Randomised Controlled Trial of Behavioural Activation versus Cognitive Behaviour Therapy for Depression
Funder: Department of Health (England)

Abstract: Background: clinical depression is one of the most common and debilitating of the psychiatric disorders a major health problem which causes substantial disability and set to become the second largest cause of global disability by 2020. Cognitive Behaviour Therapy (CBT) is the psychological treatment with most evidence of effectiveness recommended by NICE but its complexity and cost may limit its dissemination to applied NHS settings. Behavioural Activation (BA) a psychological treatment alleviating depression by focusing directly on changing behaviour may provide all the clinical benefits of CBT with fewer limitations.Question: What are the clinical effects and costs of BA compared to CBT for depressed adults at 12 and 18 monthsMethod: Non-inferiority patient level randomised controlled trial including clinical economic and process evaluationsSample: 440 people aged 18 and older with DSM Major Depressive DisorderInterventions: 20 sessions over 16 weeks with the option of four additional booster sessions of either: (a) Behavioural Activation (BA) delivered by mental health workers trained and competent in BA but with no prior specialist training in psychological interventions (b) Cognitive Behaviour Therapy (CBT) delivered by senior metal health workers with specialist training in the delivery of CBT.Outcomes: depression severity (PHQ9) at 12 & 18 months; direct and indirect costs of treatment and disease burden; health-state utility (EQ5D); DSM depression status and depression free days; Health Related Quality of Life (SF-36); the joint distribution of incremental mean costs and effects in terms of QALYs using the EQ-5D measure of health-related quality of life.Conclusions: if CBT and BA are equally effective and COBRA shows a cost benefit in terms of BA then then BA may be preferable because its simplicity in delivery and mechanism of change allows for more cost effective delivery by less specialised NHS mental health workers.


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH
Title: A double blind placebo-controlled randomised trial of the addition of the antidepressant mirtazapine for patients with depression in primary care who have not responded to at least 6 weeks of antidepressant treatment
Funder: Department of Health (England)

Abstract: Design: A two parallel group multi-centre pragmatic placebo controlled randomised trial with allocation at the level of the individual. The primary outcome will be at 12 weeks with further follow up at 6 and 12 months. Setting: Primary Care in Bristol Exeter Manchester and YorkTarget population: Adult primary care patients who meet criteria for depression after at least 6 weeks treatment with either an SSRI or an SNRI antidepressant taken at an adequate dose.Health technologies being assessed: The addition of mirtazapine to an SSRI or SNRI for the treatment of resistant depression. There is the potential for a synergistic action between SSRI/SNRI antidepressants and mirtazapine. There is evidence from previous studies that this could enhance clinical response compared to those patients receiving only an SSRI or SNRI. Mirtazapine is now off patent and inexpensive. Measurement of cost and outcomes: Primary outcome: Score on the Beck Depression Inventory (BDI) 12 weeks after randomisation measured as a continuous variable. Secondary outcomes: BDI score at 24 weeks and 12 months (continuous and binary) and at all three time points quality of life (EQ-5D) anxiety (GAD7) and adverse effects (ADEC). Adherence to medication will be measured using a brief questionnaire. We will conduct a cost-effectiveness analysis relating the costs of each strategy to the change in BDI scores at 12 weeks and 12 months; a cost-utility analysis relating the costs of each strategy to QALYs gained using the EQ-5D-5L at 12 months; and a cost consequences study at 12 months.Sample size: We estimate that a clinically important difference corresponds to about 3-4 points (0.35 standard deviations) on the BDI. With 200 participants in each group we will have 91% power to detect a difference of 0.33 standard deviations at the 5% level. Allowing for 15% loss to follow-up at 12 weeks we will need to recruit 472 patients. To detect a 50% reduction in symptoms 200 patients in each group would yield 90% power to detect a difference between 30% and 46% response or an odds ratio of 2 at a 2-sided 5% significance levelProject timetable (including recruitment rate): We have recently completed the COBALT study a trial of CBT for treatment resistant depression randomising 469 patients over 18 months at 8.4 patients per centre per month. The population to be sampled is identical. We plan to recruit 470 patients over 18 months from 96 practices in 4 centres a target of 7 patients randomised per month Year 1: Study set up. Months 7-12: recruitment begins for both trial and qualitative study. Follow up for primary outcome beginsYear 2: recruitment continues for 12 months. Follow up for outcomes at all three time points throughout the year. Recruitment ends Years 3 &4: complete follow up: analysis writing up and dissemination


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: MeASURe: Measurement in autism spectrum disorder under review.
Funder: Department of Health (England)

Abstract: Increased awareness of the prevalence of autism spectrum disorder (ASD) and evidence that early intervention is effective have led to an emphasis on early diagnosis. Thus it is important that NHS education and social services provide evidence-based interventions and early support for individuals with ASD and for their families in order to improve outcomes. A continuing problem for the interpretation of early intervention research findings is the multitude of tools used in measuring outcomes. Furthermore children’s developmental pathways are very variable as found in longitudinal studies. The literature thus presents numbers of tools with varying measurement properties inconsistently used and of varying relevance to parents and professionals priorities. A review of the quality and appropriateness of tools used to monitor children’s developmental progress and assess outcomes is needed.A team of experts in ASD and in systematic reviewing will first identify the main constructs of interest through an overview of qualitative literature on parents’ priorities; survey of measurement issues of importance for clinicians and educators; consultation with individuals with ASD and with parents to consider priority outcomes for children. We will identify the tools used to measure these constructs. A systematic search of epidemiological longitudinal and intervention studies will be conducted. We will use filters to help focus on key topics and on the measures which focus on the issues raised by parents and professionals. We will then conduct a series of specific systematic reviews of studies of measurement properties within the identified outcome domains using the COSMIN methodology. Finally through discussion and consensus with parents professionals researchers in ASD and method experts in the team we will propose a battery of tools for future use in intervention studies and monitoring of progress.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MENTAL HEALTH
Title: Risks and benefits of psychotropic medication in pregnancy
Funder: Department of Health (England)

Abstract: Longitudinal observational study of women with psychoses who are in receipt of psychotropic medication using data from The Health Improvement Network (THIN) and General Practice Research Database (GPRD). These databases include longitudinal clinical and prescribing records for more than 10% of the UK population. SETTING: United Kingdom General PracticeTARGET GROUP: Women with psychosis (bipolar disorder schizophrenia or overlap syndromes) who are in receipt of antipsychotics lithium and anticonvulsant mood stabilisers and who become pregnant.HEALTH TECHNOLOGIES: Prescriptions of: a) lithium b) AEDs c) typical and atypical antipsychotics.OUTCOMES: Quantity of prescribed psychotropic medication before during pregnancy and after delivery. Time to discontinuation and restarting of medication. Markers for change of severity of illness including psychiatric hospitalisation psychosis suicide and suicide attempts.Foetal losses neonatal death preeclampsia major congenital anomalies preterm birth low birth weight low weight for gestation low Apgar scores maternal and child renal problems


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH
Title: Alcohol refusal skills videos - refinement and feasibility
Funder: Medical Research Council

Abstract: We are developing educational materials designed to teach 16-18 year olds skills to manage temptation and/or pressure to drink excessively. The theorised mechanism of action is that developing drink Refusal Self-Efficacy and enhancing personal resilience will better enable young people to make healthy choices about alcohol use. Our recent research employed mixed methods to develop and evaluate video resources to teach young people strategies and skills to resist alcohol. Evaluation of these materials by teachers, pupils, and alcohol service workers provided “proof of concept”, and indicated that they would make a novel contribution to school-based alcohol education. However, it was evident that aspects should be revised before assessing their impact in an intervention evaluation study. There is currently a lack of evidence as to the potential impact of video resources for alcohol education. The proposed research will involve revising the videos, finalising lesson plans, and conducting a feasibility study. It will address several aspects outlined in the call for proposals: estimating recruitment and retention rates and influences; testing acceptability and compliance; developing procedures and protocols; and identifying intervention comparators. It will also continue our use of novel approaches to intervention development.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: MENTAL HEALTH
Title: Bipolar JLA
Funder: MQ: Transforming Mental Health

Abstract: A James Lind Alliance priority setting partnership to discover from patients, carers and clinicians their research priorities about Bipolar Disorder. This project is being set up to identify unanswered questions about bipolar- its causes, diagnosis, treatment, care and prognosis. New technologies and approaches to understanding bipolar are becoming increasingly available. These advances expand the scope of research making it more important than ever that future research is guided by people with personal or professional experience of bipolar. The direction of research is often set by researchers or by the drug industry. We want to enable patients, carers, family members and the health and social care professionals who look after those with bipolar to have their say, so that future research is aligned with what matters to everyone whose life is affected by bipolar. What questions do you think researchers should be working on?


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: MENTAL HEALTH
Title: Depression: Asking the Right Questions
Funder: MQ: Transforming Mental Health

Abstract: We aim to uncover the most important issues for people directly affected by depression. These will be turned into ‘top 10’ research priorities. We will share the top 10 researchers and research funders to help guide future research into depression.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: MENTAL HEALTH