Proactive and integrated consultation-liaison psychiatry for older medical inpatients: A mixed methods description of training, care provided and clinician experience in the HOME study.

OBJECTIVES: To describe the practical experience of delivering a proactive and integrated consultation-liaison (C-L) psychiatry service model (PICLP). PICLP is designed for older medical inpatients and is explicitly biopsychosocial and discharge-focused. In this paper we report: (a) observations on the training of 15 clinicians (seven senior C-L psychiatrists and eight assisting clinicians) to deliver PICLP; (b) the care they provided to 1359 patients; (c) their experiences of working in this new way. METHOD: A mixed methods observational study using quantitative and qualitative data, collected prospectively over two years as part of The HOME Study (a randomized trial comparing PICLP with usual care). RESULTS: The clinicians were successfully trained to deliver PICLP according to the service manual. They proactively assessed all patients and found that most had multiple biopsychosocial problems impeding their timely discharge from hospital. They integrated with ward teams to provide a range of interventions aimed at addressing these problems. Delivering PICLP took a modest amount of clinical time, and the clinicians experienced it as both clinically valuable and professionally rewarding. CONCLUSION: The experience of delivering PICLP highlights the special role that C-L psychiatry clinicians, working in a proactive and integrated way, can play in medical care.

Depression interventions for individuals with coronary artery disease - Cost-effectiveness calculations from an Irish perspective.

BACKGROUND: A substantial proportion of individuals with coronary artery disease experience moderate or severe acute depression that requires treatment. We assessed the cost-effectiveness of four interventions for depression in individuals with coronary artery disease. METHODS: We assessed effectiveness of pharmacotherapy, psychotherapy, collaborative care and exercise as remission rate after 8 and 26 weeks using estimates from a recent network meta-analysis. The cost assessment included standard doses of antidepressants, contact frequency, and staff time per contact. Unit costs were calculated as health services' purchase price for pharmaceuticals and mid-point staff salaries obtained from the Irish Health Service Executive and validated by clinical staff. Incremental cost-effectiveness ratios were calculated as the incremental costs over incremental remissions compared to usual care. High- and low-cost scenarios and sensitivity analysis were performed with changed contact frequencies, and assuming individual vs. group psychotherapy or exercise. RESULTS: After 8 weeks, the estimated incremental cost-effectiveness ratio was lowest for group exercise (€526 per remission), followed by pharmacotherapy (€589), individual psychotherapy (€3117) and collaborative care (€4964). After 26 weeks, pharmacotherapy was more cost-effective (€591) than collaborative care (€7203) and individual psychotherapy (€9387); no 26-week assessment for exercise was possible. Sensitivity analysis showed that group psychotherapy could be most cost-effective after 8 weeks (€519) and cost-effective after 26 weeks (€1565); however no group psychotherapy trials were available investigating its effectiveness. DISCUSSION: Large variation in incremental cost-effectiveness ratios was seen. With the current assumptions, the most cost-effective depression intervention for individuals with coronary artery disease after 8 weeks was group exercise.

Hybrid Systematic Review and Network Meta-Analysis of Randomized Controlled Trials of Interventions for Depressive Symptoms in Patients With Coronary Artery Disease.

OBJECTIVE: Depression is common in patients with coronary artery disease (CAD) and is associated with poor outcomes. Although different treatments are available, it is unclear which are best or most acceptable to patients, so we conducted a network meta-analysis of evidence from randomized controlled trials (RCTs) of different depression treatments to ascertain relative efficacy. METHODS: We searched for systematic reviews of RCTs of depression treatments in CAD and updated these with a comprehensive search for recent individual RCTs. RCTs comparing depression treatments (pharmacological, psychotherapeutic, combined pharmacological/psychotherapeutic, exercise, collaborative care) were included. Primary outcomes were acceptability (dropout rate) and change in depressive symptoms 8 week after treatment commencement. Change in 26-week depression and mortality were secondary outcomes. Frequentist, random-effects network meta-analysis was used to synthesize the evidence, and evidence quality was evaluated following Grading of Recommendations, Assessment, Development and Evaluations recommendations. RESULTS: Thirty-three RCTs (7240 participants) provided analyzable data. All treatments were equally acceptable. At 8 weeks, combination therapy (1 study), exercise (1 study), and antidepressants (10 studies) yielded the strongest effects versus comparators. At 26 weeks, antidepressants were consistently effective, but psychotherapy was only effective versus usual care. There were no differences in treatment groups for mortality. Grading of Recommendations, Assessment, Development and Evaluations ratings ranged from very low to low. CONCLUSIONS: Overall, the evidence was limited and biased. Although all treatments for post-CAD depression were equally acceptable, antidepressants have the most robust evidence base and should be the first-line treatment. Combinations of antidepressants and psychotherapy, along with exercise, could be more effective than antidepressants alone but require further rigorous, multiarm intervention trials.Systematic Review Registration: CRD42018108293 (International Prospective Register of Systematic Reviews).

Capacity challenges in water quality monitoring: understanding the role of human development.

Monitoring the qualitative status of freshwaters is an important goal of the international community, as stated in the Sustainable Development Goal (SDGs) indicator 6.3.2 on good ambient water quality. Monitoring data are, however, lacking in many countries, allegedly because of capacity challenges of less-developed countries. So far, however, the relationship between human development and capacity challenges for water quality monitoring have not been analysed systematically. This hinders the implementation of fine-tuned capacity development programmes for water quality monitoring. Against this background, this study takes a global perspective in analysing the link between human development and the capacity challenges countries face in their national water quality monitoring programmes. The analysis is based on the latest data on the human development index and an international online survey amongst experts from science and practice. Results provide evidence of a negative relationship between human development and the capacity challenges to meet SDG 6.3.2 monitoring requirements. This negative relationship increases along the course of the monitoring process, from defining the enabling environment, choosing parameters for the collection of field data, to the analytics and analysis of five commonly used parameters (DO, EC, pH, TP and TN). Our assessment can be used to help practitioners improve technical capacity development activities and to identify and target investment in capacity development for monitoring.

Mental health in UK Biobank - development, implementation and results from an online questionnaire completed by 157 366 participants: a reanalysis.

BACKGROUND: UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential. AIMS: Describe the development, implementation and results of this questionnaire. METHOD: An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use. RESULTS: A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45-82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation. CONCLUSIONS: The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.

Patients' experiences of seeking help for emotional concerns in primary care: doctor as drug, detective and collaborator.

BACKGROUND: NICE guidelines for the management of emotional concerns in primary care emphasise the importance of communication and a trusting relationship, which is difficult to operationalise in practice. Current pressures in the NHS mean that it is important to understand care from a patient perspective. This study aimed to explore patients' experiences of primary care consultations for emotional concerns and what patients valued when seeking care from their GP. METHODS: Eighteen adults with experience of consulting a GP for emotional concerns participated in 4 focus groups. Data were analysed thematically. RESULTS: (1) Doctor as Drug: Patients' relationship with their GP was considered therapeutic with continuity particularly valued. (2) Doctor as Detective and Validator: Patients were often puzzled by their symptoms, not recognising their emotional concerns. GPs needed to play the role of detective by exploring not just symptoms, but the person and their life circumstances. GPs were crucial in helping patients understand and validate their emotional concerns. (3) Doctor as Collaborator: Patients prefer a collaborative partnership, but often need to relinquish involvement because they are too unwell, or take a more active role because they feel GPs are ill-equipped or under too much pressure to help. Patients valued: GPs booking their follow up appointments; acknowledgement of stressful life circumstances; not relying solely on medication. CONCLUSIONS: Seeking help for emotional concerns is challenging due to stigma and unfamiliar symptoms. GPs can support disclosure and understanding of emotional concerns by fully exploring and validating patients' concerns, taking into account patients' life contexts. This process of exploration and validation forms the foundation of a curative, trusting GP-patient relationship. A trusting relationship, with an emphasis on empathy and understanding, can make patients more able to share involvement in their care with GPs. This process is cyclical, as patients feel that their GP is caring, interested, and treating them as a person, further strengthening their relationship. NICE guidance should acknowledge the importance of empathy and validation when building an effective GP-patient partnership, and the role this has in supporting patients' involvement in their care.

Barriers and facilitators to GP-patient communication about emotional concerns in UK primary care: a systematic review.

BACKGROUND: In the UK, general practitioners (GPs) are the most commonly used providers of care for emotional concerns. OBJECTIVE: To update and synthesize literature on barriers and facilitators to GP-patient communication about emotional concerns in UK primary care. DESIGN: Systematic review and qualitative synthesis. METHOD: We conducted a systematic search on MEDLINE (OvidSP), PsycInfo and EMBASE, supplemented by citation chasing. Eligible papers focused on how GPs and adult patients in the UK communicated about emotional concerns. Results were synthesized using thematic analysis. RESULTS: Across 30 studies involving 342 GPs and 720 patients, four themes relating to barriers were: (i) emotional concerns are difficult to disclose; (ii) tension between understanding emotional concerns as a medical condition or arising from social stressors; (iii) unspoken assumptions about agency resulting in too little or too much involvement in decisions and (iv) providing limited care driven by little time. Three facilitative themes were: (v) a human connection improves identification of emotional concerns and is therapeutic; (vi) exploring, explaining and negotiating a shared understanding or guiding patients towards new understandings and (vii) upfront information provision and involvement manages expectations about recovery and improves engagement in treatment. CONCLUSION: The findings suggest that treatment guidelines should acknowledge: the therapeutic value of a positive GP-patient relationship; that diagnosis is a two-way negotiated process rather than an activity strictly in the doctor's domain of expertise; and the value of exploring and shaping new understandings about patients' emotional concerns and their management.

"Every structure we're taught goes out the window": General practitioners' experiences of providing help for patients with emotional concerns'.

Up to 40% of general practitioners (GP) consultations contain an emotional component. General practitioners (GPs) have to provide care with limited time and resources. This qualitative study aimed to explore how GPs care for patients experiencing emotional concerns within the constraints of busy clinical practice. Seven GPs participated in three focus groups. Groups were recorded, transcribed and analysed thematically. Three themes were identified. (a) Collaboratively negotiated diagnosis: How patients' emotional concerns are understood and managed is the result of a negotiation between patient and GP belief models and the availability of treatments including talking therapy. (b) Doctor as drug: Not only is a continuous relationship between GPs and patients therapeutic in its own right, it is also necessary to effectively diagnose and engage patients in treatment as patients may experience stigma regarding emotional concerns. (c) Personal responsibility and institutional pressure: GPs feel personally responsible for supporting patients through their care journey, however, they face barriers due to lack of time and pressure from guidelines. GPs are forced to prioritise high-risk patients and experience an emotional toll. In conclusion, guidelines focus on diagnosis and a stepped-care model, however, this assumes diagnosis is relatively straightforward. GPs and patients have different models of psychological distress. This and the experience of stigma mean that establishing rapport is an important step before the GP and patient negotiate openly and develop a shared understanding of the problem. This takes time and emotional resources to do well. Longer consultations, continuity of care and formal supervision for GPs could enable them to better support patients.

The role of relapse prevention for depression in collaborative care: A systematic review.

BACKGROUND: Relapse (the re-emergence of depression symptoms before full recovery) is common in depression and relapse prevention strategies are not well researched in primary care settings. Collaborative care is effective for treating acute phase depression but little is known about the use of relapse prevention strategies in collaborative care. We undertook a systematic review to identify and characterise relapse prevention strategies in the context of collaborative care. METHODS: We searched for Randomised Controlled Trials (RCTs) of collaborative care for depression. In addition to published material, we obtained provider and patient manuals from authors to provide more detail on intervention content. We reported the extent to which collaborative care interventions addressed four relapse prevention components. RESULTS: 93 RCTs were identified. 31 included a formal relapse prevention plan; 42 had proactive monitoring and follow-up after the acute phase; 39 reported strategies for optimising sustained medication adherence; and 20 of the trials reported psychological or psycho-educational treatments persisting beyond the acute phase or focussing on long-term health/relapse prevention. 30 (32.3%) did not report relapse prevention approaches. LIMITATIONS: We did not receive trial materials for approximately half of the trials, which limited our ability to identify relevant features of intervention content. CONCLUSION: Relapse is a significant risk amongst people treated for depression and interventions are needed that specifically address and minimise this risk. Given the advantages of collaborative care as a delivery system for depression care, there is scope for more consistency and increased effort to implement and evaluate relapse prevention strategies.

Understanding rivers and their social relations: A critical step to advance environmental water management.

River flows connect people, places, and other forms of life, inspiring and sustaining diverse cultural beliefs, values, and ways of life. The concept of environmental flows provides a framework for improving understanding of relationships between river flows and people, and for supporting those that are mutually beneficial. Nevertheless, most approaches to determining environmental flows remain grounded in the biophysical sciences. The newly revised Brisbane Declaration and Global Action Agenda on Environmental Flows (2018) represents a new phase in environmental flow science and an opportunity to better consider the co-constitution of river flows, ecosystems, and society, and to more explicitly incorporate these relationships into river management. We synthesize understanding of relationships between people and rivers as conceived under the renewed definition of environmental flows. We present case studies from Honduras, India, Canada, New Zealand, and Australia that illustrate multidisciplinary, collaborative efforts where recognizing and meeting diverse flow needs of human populations was central to establishing environmental flow recommendations. We also review a small body of literature to highlight examples of the diversity and interdependencies of human-flow relationships-such as the linkages between river flow and human well-being, spiritual needs, cultural identity, and sense of place-that are typically overlooked when environmental flows are assessed and negotiated. Finally, we call for scientists and water managers to recognize the diversity of ways of knowing, relating to, and utilizing rivers, and to place this recognition at the center of future environmental flow assessments. This article is categorized under: Water and Life > Conservation, Management, and Awareness Human Water > Water Governance Human Water > Water as Imagined and Represented.

Perseverative negative thinking predicts depression in people with acute coronary syndrome.

OBJECTIVE: Depression is common in people who have experienced recent Acute Coronary Syndrome (ACS), and predicts worse medical outcomes. Mechanisms underpinning the development of depression and its association with poor medical outcomes are unclear however. The aim of this study was to investigate the role of perseverative negative thinking (e.g. worry and rumination) in predicting depression in people with recent ACS. METHODS: Adults attending specialist inpatient and outpatient cardiology services who had recently experienced ACS were invited to participate in this observational prospective cohort study. Questionnaire assessments were completed within 6months of index ACS (baseline), then 2months and 6months later. RESULTS: 169 participants (131 male (78%), median age 68 (±16) years) completed baseline questionnaires, and 111 completed follow-ups. After controlling for the effects of key covariates, baseline rumination was a significant predictor of depression at 6months, accounting for 2% of the variance in depression. This association was partially mediated by poor problem-solving ability and lack of social support. Neither worry nor rumination at baseline were significant predictors of quality of life at 6months. CONCLUSIONS: Rumination is a significant independent predictor of depression, and this association may be partially explained by deficits in problem-solving ability and reduced social support. Both rumination and problem solving may provide useful targets for the development of evidence-based interventions to reduce depression among people with coronary heart disease.

Factors associated with depression in people with inflammatory bowel disease: The relationship between active disease and biases in neurocognitive processing.

BACKGROUND: Depression is common among people with inflammatory bowel disease (IBD), though the causes remain unclear. We conducted a cross-sectional study to investigate the role of emotional processing biases in contributing to depression among people with IBD. MATERIALS AND METHODS: One hundred and twenty outpatients with IBD were recruited and: (a) completed questionnaires to record: age, sex, social support, socioeconomic status, anxiety and depression (n = 104), (b) underwent assessments of biases in emotional recognition (n = 112), emotional memory and reinforcement learning (c) had recorded from clinical records: type of IBD, duration of IBD, IBD activity and (d) provided blood for high-sensitivity C-reactive protein levels (n = 99). KEY RESULTS: Sixty-eight participants had Crohn's disease and 49 had ulcerative colitis. Of these, 35 had active disease and 26 had depression. Those with depression were more likely to be female, lack social support, have active disease, be taking corticosteroids but not TNF-alpha inhibitors and exhibit less positive emotional recognition bias. On multivariable regression analysis, depression was associated independently with lack of social support (unstandardized regression coefficient (B) = -1.40, P = 0.02) and increased disease activity (B = 1.29, P = 0.03). Causal steps analysis was consistent with less positive emotional recognition bias partially mediating the effects of disease activity on depression. CONCLUSIONS AND INFERENCES: This is the first study to demonstrate links between disease activity and less positive biases in emotional recognition that could explain higher rates of depression among people with active IBD. Future prospective studies are required to confirm the effects of emotional processing biases in depression and allow stronger causal inferences to be drawn.

Impact of telephone delivered case-management on the effectiveness of collaborative care for depression and anti-depressant use: A systematic review and meta-regression.

BACKGROUND: The health service delivery framework collaborative care is an effective intervention for depression. However, uncertainties remain about how to optimise its delivery at scale. Structured case management is a core component of collaborative care; its delivery via the telephone may improve access. AIMS: To examine using meta-regression if telephone delivered case management diminishes the clinical effectiveness of collaborative care on depressive symptoms and anti-depressant use relative to face-to-face delivery methods. METHODS: Randomised controlled trials were eligible if they included collaborative care interventions for adults with depression identified using self-report measures or diagnostic interviews and reported depression outcomes. Sociodemographics, intervention characteristics, depressive symptoms, and anti-depressant use were extracted. Random effects univariable and multivariable meta-regression analyses were used to examine the moderating effect of telephone delivered case-management on outcomes. RESULTS: Ninety-four trials were identified comprising of 103 comparisons across 24, 132 participants with depression outcomes and 67 comparisons from 15,367 participants with anti-depressant use outcomes. Telephone delivered case management did not diminish the effects of collaborative care on depressive symptoms (ß = -0.01, 95% CI -0.12 to 0.10; p = 0.86). Telephone delivered case management decreased anti-depressant medication use (relative risk 0.76, 95% CI 0.63 to 0.92; p = 0.005); this effect remained when assessed simultaneously alongside other study-level moderators of collaborative care. CONCLUSION: Using remote platforms such as the telephone to deliver case management may be a feasible way to implement collaborative care with no loss of effectiveness on depressive symptoms. However, adherence to anti-depressant medication may decrease when telephone case management is used.

Interventions to improve the mental health of children and young people with long-term physical conditions: linked evidence syntheses.

BACKGROUND: Although mental health difficulties can severely complicate the lives of children and young people (CYP) with long-term physical conditions (LTCs), there is a lack of evidence about the effectiveness of interventions to treat them. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of interventions aiming to improve the mental health of CYP with LTCs (review 1) and explore the factors that may enhance or limit their delivery (review 2). DATA SOURCES: For review 1, 13 electronic databases were searched, including MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Science Citation Index. For review 2, MEDLINE, PsycINFO and CINAHL were searched. Supplementary searches, author contact and grey literature searches were also conducted. REVIEW METHODS: The first systematic review sought randomised controlled trials (RCTs) and economic evaluations of interventions to improve elevated symptoms of mental ill health in CYP with LTCs. Effect sizes for each outcome were calculated post intervention (Cohen's d). When appropriate, random-effects meta-analyses produced pooled effect sizes (d). Review 2 located primary qualitative studies exploring experiences of CYP with LTCs, their families and/or practitioners, regarding interventions aiming to improve the mental health and well-being of CYP with LTCs. Synthesis followed the principles of metaethnography. An overarching synthesis integrated the findings from review 1 and review 2 using a deductive approach. End-user involvement, including topic experts and CYP with LTCs and their parents, was a feature throughout the project. RESULTS: Review 1 synthesised 25 RCTs evaluating 11 types of intervention, sampling 12 different LTCs. Tentative evidence from seven studies suggests that cognitive-behavioural therapy interventions could improve the mental health of CYP with certain LTCs. Intervention-LTC dyads were diverse, with few opportunities to meta-analyse. No economic evaluations were located. Review 2 synthesised 57 studies evaluating 21 types of intervention. Most studies were of individuals with cancer, a human immunodeficiency virus (HIV) infection or mixed LTCs. Interventions often aimed to improve broader mental health and well-being, rather than symptoms of mental health disorder. The metaethnography identified five main constructs, described in an explanatory line of argument model of the experience of interventions. Nine overarching synthesis categories emerged from the integrated evidence, raising implications for future research. LIMITATIONS: Review 1 conclusions were limited by the lack of evidence about intervention effectiveness. No relevant economic evaluations were located. There were no UK studies included in review 1, limiting the applicability of findings. The mental health status of participants in review 2 was usually unknown, limiting comparability with review 1. The different evidence identified by the two systematic reviews challenged the overarching synthesis. CONCLUSIONS: There is a relatively small amount of comparable evidence for the effectiveness of interventions for the mental health of CYP with LTCs. Qualitative evidence provided insight into the experiences that intervention deliverers and recipients valued. Future research should evaluate potentially effective intervention components in high-quality RCTs integrating process evaluations. End-user involvement enriched the project. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001716. FUNDING: The National Institute for Health Research (NIHR) Health Technology Assessment programme and the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula.

Many children and young people with a long-term physical health condition also experience feelings of depression, anxiety and other mental health issues that affect their day-to-day life, their family and others around them. This review investigates whether or not interventions (treatments, strategies and resources) can help children and young people with their mental health. The study also reviewed studies that explored the attitudes and experiences of those involved in receiving or delivering similar interventions. The study found 25 publications that evaluated 11 different types of interventions, including cognitive­behavioural therapy (seven studies) and music therapy (one study). There were some positive effects for the strategies tested on both mental health and other outcomes, but, because the studies were often small, exact effects were uncertain. Many of the studies were not very well designed or carried out and differences between research designs meant that it was hard to compare different studies. The study found 57 publications that explored experiences of interventions. Analysis suggested that it is important that strategies involve building good relationships and are delivered in what feels like a safe space. Participants in studies tended to like interventions that provided social support and helped them feel better about living with a long-term physical condition. Successful interventions were viewed as accessible and engaging. These studies were often conducted well, but they focused on the range of interventions rather than the review evaluating how well interventions work. There are many gaps in the research carried out so far. Some long-term conditions affecting children and young people have not been the subject of studies of mental health interventions, and some important outcomes, such as school attendance and self-care, have not been assessed. More carefully designed UK research consulting children and young people, parents and practitioners is needed before it can be clear what works for children with particular physical conditions to help their mental health, and why.

Network meta-analysis of randomised trials of pharmacological, psychotherapeutic, exercise and collaborative care interventions for depressive symptoms in patients with coronary artery disease: hybrid systematic review of systematic reviews protocol.

BACKGROUND: Depression is common in patients with coronary artery disease (CAD) and is associated with poorer outcomes and higher costs. Several randomised controlled trials (RCTs) targeting depression, of various modalities (including pharmacological, psychotherapeutic and other approaches), have been conducted and summarised in pairwise meta-analytic reviews. However, no study has considered the cumulative evidence within a network, which can provide valuable indirect comparisons and information about the relative efficacy of interventions. Therefore, we will adopt a review of review methodology to develop a network meta-analysis (NMA) of depression interventions for depression in CAD. METHODS: We will search relevant databases from inception for systematic reviews of RCTs of depression treatments for people with CAD, supplementing this with comprehensive searches for recent or ongoing studies. We will extract data from and summarise characteristics of individual RCTs, including participants, study characteristics, outcome measures and adverse events. Cochrane risk of bias ratings will also be extracted or if not present will be conducted by the authors. RCTs that compare depression treatments (grouped as pharmacological, psychotherapeutic, combined pharmacological/psychotherapeutic, exercise, collaborative care) to placebo, usual care, waitlist control or attention controls, or directly in head-to-head comparisons, will be included. Primary outcomes will be the change in depressive symptoms (summarised with a standardised mean difference) and treatment acceptability (treatment discontinuation: % of people who withdrew). Secondary outcomes will include change in 6-month depression outcomes, health-related quality of life (HRQoL), mortality, cardiovascular morbidity, health services use and adverse events. Secondary analyses will form further networks with individual anti-depressants and psychotherapies. We will use frequentist, random effects multivariate network meta-analysis to synthesise the evidence for depression intervention and to achieve a ranking of treatments, using Stata. Rankograms and surface under the cumulative ranking curves will be used for treatment ranking. Local and global methods will evaluate consistency. GRADE will be used to assess evidence quality for primary outcomes. DISCUSSION: The present review will address uncertainties about the evidence in terms of depression management in CAD and may allow for a ranking of treatments, including providing important information for future research efforts. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018108293.

Structured lifestyle education for people with schizophrenia, schizoaffective disorder and first-episode psychosis (STEPWISE): randomised controlled trial.

BACKGROUND: Obesity is a major challenge for people with schizophrenia.AimsWe assessed whether STEPWISE, a theory-based, group structured lifestyle education programme could support weight reduction in people with schizophrenia. METHOD: In this randomised controlled trial (study registration: ISRCTN19447796), we recruited adults with schizophrenia, schizoaffective disorder or first-episode psychosis from ten mental health organisations in England. Participants were randomly allocated to the STEPWISE intervention or treatment as usual. The 12-month intervention comprised four 2.5 h weekly group sessions, followed by 2-weekly maintenance contact and group sessions at 4, 7 and 10 months. The primary outcome was weight change after 12 months. Key secondary outcomes included diet, physical activity, biomedical measures and patient-related outcome measures. Cost-effectiveness was assessed and a mixed-methods process evaluation was included. RESULTS: Between 10 March 2015 and 31 March 2016, we recruited 414 people (intervention 208, usual care 206) with 341 (84.4%) participants completing the trial. At 12 months, weight reduction did not differ between groups (mean difference 0.0 kg, 95% CI -1.6 to 1.7, P = 0.963); physical activity, dietary intake and biochemical measures were unchanged. STEPWISE was well-received by participants and facilitators. The healthcare perspective incremental cost-effectiveness ratio was £246 921 per quality-adjusted life-year gained. CONCLUSIONS: Participants were successfully recruited and retained, indicating a strong interest in weight interventions; however, the STEPWISE intervention was neither clinically nor cost-effective. Further research is needed to determine how to manage overweight and obesity in people with schizophrenia.Declaration of interestR.I.G.H. received fees for lecturing, consultancy work and attendance at conferences from the following: Boehringer Ingelheim, Eli Lilly, Janssen, Lundbeck, Novo Nordisk, Novartis, Otsuka, Sanofi, Sunovion, Takeda, MSD. M.J.D. reports personal fees from Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceuticals International Inc.; and, grants from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Janssen. K.K. has received fees for consultancy and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Servier and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. K.K. has received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme and Novo Nordisk. D.Sh. is expert advisor to the NICE Centre for guidelines; board member of the National Collaborating Centre for Mental Health (NCCMH); clinical advisor (paid consultancy basis) to National Clinical Audit of Psychosis (NCAP); views are personal and not those of NICE, NCCMH or NCAP. J.P. received personal fees for involvement in the study from a National Institute for Health Research (NIHR) grant. M.E.C. and Y.D. report grants from NIHR Health Technology Assessment, during the conduct of the study; and The Leicester Diabetes Centre, an organisation (employer) jointly hosted by an NHS Hospital Trust and the University of Leicester and who is holder (through the University of Leicester) of the copyright of the STEPWISE programme and of the DESMOND suite of programmes, training and intervention fidelity framework that were used in this study. S.R. has received honorarium from Lundbeck for lecturing. F.G. reports personal fees from Otsuka and Lundbeck, personal fees and non-financial support from Sunovion, outside the submitted work; and has a family member with professional links to Lilly and GSK, including shares. F.G. is in part funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research & Care Funding scheme, by the Maudsley Charity and by the Stanley Medical Research Institute and is supported by the by the Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Combining mirtazapine with SSRIs or SNRIs for treatment-resistant depression: the MIR RCT.

BACKGROUND: Depression is usually managed in primary care and antidepressants are often the first-line treatment, but only half of those treated respond to a single antidepressant. OBJECTIVES: To investigate whether or not combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants results in better patient outcomes and more efficient NHS care than SNRI or SSRI therapy alone in treatment-resistant depression (TRD). DESIGN: The MIR trial was a two-parallel-group, multicentre, pragmatic, placebo-controlled randomised trial with allocation at the level of the individual. SETTING: Participants were recruited from primary care in Bristol, Exeter, Hull/York and Manchester/Keele. PARTICIPANTS: Eligible participants were aged ≥ 18 years; were taking a SSRI or a SNRI antidepressant for at least 6 weeks at an adequate dose; scored ≥ 14 points on the Beck Depression Inventory-II (BDI-II); were adherent to medication; and met the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, criteria for depression. INTERVENTIONS: Participants were randomised using a computer-generated code to either oral mirtazapine or a matched placebo, starting at a dose of 15 mg daily for 2 weeks and increasing to 30 mg daily for up to 12 months, in addition to their usual antidepressant. Participants, their general practitioners (GPs) and the research team were blind to the allocation. MAIN OUTCOME MEASURES: The primary outcome was depression symptoms at 12 weeks post randomisation compared with baseline, measured as a continuous variable using the BDI-II. Secondary outcomes (at 12, 24 and 52 weeks) included response, remission of depression, change in anxiety symptoms, adverse events (AEs), quality of life, adherence to medication, health and social care use and cost-effectiveness. Outcomes were analysed on an intention-to-treat basis. A qualitative study explored patients' views and experiences of managing depression and GPs' views on prescribing a second antidepressant. RESULTS: There were 480 patients randomised to the trial (mirtazapine and usual care, n = 241; placebo and usual care, n = 239), of whom 431 patients (89.8%) were followed up at 12 weeks. BDI-II scores at 12 weeks were lower in the mirtazapine group than the placebo group after adjustment for baseline BDI-II score and minimisation and stratification variables [difference -1.83 points, 95% confidence interval (CI) -3.92 to 0.27 points; p = 0.087]. This was smaller than the minimum clinically important difference and the CI included the null. The difference became smaller at subsequent time points (24 weeks: -0.85 points, 95% CI -3.12 to 1.43 points; 12 months: 0.17 points, 95% CI -2.13 to 2.46 points). More participants in the mirtazapine group withdrew from the trial medication, citing mild AEs (46 vs. 9 participants). CONCLUSIONS: This study did not find convincing evidence of a clinically important benefit for mirtazapine in addition to a SSRI or a SNRI antidepressant over placebo in primary care patients with TRD. There was no evidence that the addition of mirtazapine was a cost-effective use of NHS resources. GPs and patients were concerned about adding an additional antidepressant. LIMITATIONS: Voluntary unblinding for participants after the primary outcome at 12 weeks made interpretation of longer-term outcomes more difficult. FUTURE WORK: Treatment-resistant depression remains an area of important, unmet need, with limited evidence of effective treatments. Promising interventions include augmentation with atypical antipsychotics and treatment using transcranial magnetic stimulation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN06653773; EudraCT number 2012-000090-23. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 63. See the NIHR Journals Library website for further project information.

Mirtazapine added to SSRIs or SNRIs for treatment resistant depression in primary care: phase III randomised placebo controlled trial (MIR).

OBJECTIVE: To investigate the effectiveness of combining mirtazapine with serotonin-noradrenaline reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI) antidepressants for treatment resistant depression in primary care. DESIGN: Two parallel group multicentre phase III randomised placebo controlled trial. SETTING: 106 general practices in four UK sites; Bristol, Exeter, Hull, and Keele/North Staffs, August 2013 to October 2015. PARTICIPANTS: 480 adults aged 18 or more years who scored 14 or more on the Beck depression inventory, second revision, fulfilled ICD-10 (international classification of diseases, 10th revision) criteria for depression, and had used an SSRI or SNRI for at least six weeks but were still depressed. 241 were randomised to mirtazapine and 239 to placebo, both given in addition to usual SSRI or SNRI treatment. Participants were stratified by centre and minimised by baseline Beck depression inventory score, sex, and current psychological therapy. They were followed up at 12, 24, and 52 weeks. 431 (89.8%) were included in the (primary) 12 week follow-up. MAIN OUTCOME MEASURES: Depressive symptoms at 12 weeks after randomisation, measured using the Beck depression inventory II score as a continuous variable. Secondary outcomes included measures of anxiety, quality of life, and adverse effects at 12, 24, and 52 weeks. RESULTS: Beck depression inventory II scores at 12 weeks were lower in the mirtazapine group after adjustment for baseline scores and minimisation or stratification variables, although the confidence interval included the null (mean (SD) scores at 12 weeks: 18.0 (12.3) in the mirtazapine group, 19.7 (12.4) in the placebo group; adjusted difference between means -1.83 (95% confidence interval -3.92 to 0.27); P=0.09). Adverse effects were more common in the mirtazapine group and were associated with the participants stopping the trial drug. CONCLUSION: This study did not find evidence of a clinically important benefit for mirtazapine in addition to an SSRI or SNRI over placebo in a treatment resistant group of primary care patients with depression. This remains an area of important unmet need where evidence of effective treatment options is limited. TRIAL REGISTRATION: Current Controlled Trials ISRCTN06653773.

Erratum: Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants - CORRIGENDUM.

[This corrects the article DOI: 10.1192/bjo.2018.12.].