Angharad N de Cates, Catherine J Harmer, Paul J Harrison, Philip J Cowen, Anton Emmanuel, Simon Travis, Susannah E Murphy, Maxime Taquet
{"title":"Association between a selective 5-HT<sub>4</sub> receptor agonist and incidence of major depressive disorder: emulated target trial.","authors":"Angharad N de Cates, Catherine J Harmer, Paul J Harrison, Philip J Cowen, Anton Emmanuel, Simon Travis, Susannah E Murphy, Maxime Taquet","doi":"10.1192/bjp.2024.97","DOIUrl":"10.1192/bjp.2024.97","url":null,"abstract":"<p><strong>Background: </strong>The serotonin 4 receptor (5-HT<sub>4</sub>R) is a promising target for the treatment of depression. Highly selective 5-HT<sub>4</sub>R agonists, such as prucalopride, have antidepressant-like and procognitive effects in preclinical models, but their clinical effects are not yet established.</p><p><strong>Aims: </strong>To determine whether prucalopride (a 5-HT<sub>4</sub>R agonist and licensed treatment for constipation) is associated with reduced incidence of depression in individuals with no past history of mental illness, compared with anti-constipation agents with no effect on the central nervous system.</p><p><strong>Method: </strong>Using anonymised routinely collected data from a large-scale USA electronic health records network, we conducted an emulated target trial comparing depression incidence over 1 year in individuals without prior diagnoses of major mental illness, who initiated treatment with prucalopride versus two alternative anti-constipation agents that act by different mechanisms (linaclotide and lubiprostone). Cohorts were matched for 121 covariates capturing sociodemographic factors, and historical and/or concurrent comorbidities and medications. The primary outcome was a first diagnosis of major depressive disorder (ICD-10 code F32) within 1 year of the index date. Robustness of the results to changes in model and population specification was tested. Secondary outcomes included a first diagnosis of six other neuropsychiatric disorders.</p><p><strong>Results: </strong>Treatment with prucalopride was associated with significantly lower incidence of depression in the following year compared with linaclotide (hazard ratio 0.87, 95% CI 0.76-0.99; <i>P</i> = 0.038; <i>n</i> = 8572 in each matched cohort) and lubiprostone (hazard ratio 0.79, 95% CI 0.69-0.91; <i>P</i> < 0.001; <i>n</i> = 8281). Significantly lower risks of all mood disorders and psychosis were also observed. Results were similar across robustness analyses.</p><p><strong>Conclusions: </strong>These findings support preclinical data and suggest a role for 5-HT<sub>4</sub>R agonists as novel agents in the prevention of major depression. These findings should stimulate randomised controlled trials to confirm if these agents can serve as a novel class of antidepressant within a clinical setting.</p>","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":" ","pages":"371-378"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emilio Fernandez-Egea, Robert J Flanagan, David Taylor, Fiona Gaughran, Stephen M Lawrie, Christopher Jenkins, Shubulade Smith, Oliver D Howes, James H MacCabe
{"title":"Mortality associated with clozapine: what is the evidence?","authors":"Emilio Fernandez-Egea, Robert J Flanagan, David Taylor, Fiona Gaughran, Stephen M Lawrie, Christopher Jenkins, Shubulade Smith, Oliver D Howes, James H MacCabe","doi":"10.1192/bjp.2024.88","DOIUrl":"10.1192/bjp.2024.88","url":null,"abstract":"<p><p>While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.</p>","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":" ","pages":"357-359"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The potential unintended consequences of Mental Health Act reforms in England and Wales on people with intellectual disability and/or autism: commentary, author response, Tromans et al.","authors":"Samuel Tromans, Indermeet Sawhney, Rohit Shankar","doi":"10.1192/bjp.2024.58","DOIUrl":"https://doi.org/10.1192/bjp.2024.58","url":null,"abstract":"","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":"225 3","pages":"414-415"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tessa Lomax, Joseph Butler, Andrea Cipriani, Ilina Singh
{"title":"Effect of nature on the mental health and well-being of children and adolescents: meta-review.","authors":"Tessa Lomax, Joseph Butler, Andrea Cipriani, Ilina Singh","doi":"10.1192/bjp.2024.109","DOIUrl":"10.1192/bjp.2024.109","url":null,"abstract":"<p><strong>Background: </strong>Urbanisation is taking place worldwide and rates of mental illness are rising. There has been increasing interest in 'nature' and how it may benefit mental health and well-being.</p><p><strong>Aims: </strong>To understand how the literature defines nature; what the characteristics of the nature intervention are; what mental health and well-being outcomes are being measured; and what the evidence shows, in regard to how nature affects the mental health and well-being of children and adolescents.</p><p><strong>Method: </strong>A meta-review was conducted, searching three databases for relevant primary and secondary studies, using key search terms including 'nature' and 'mental health' and 'mental well-being'. Inclusion criteria included published English-language studies on the child and adolescent population. Authors identified the highest quality evidence from studies meeting the inclusion criteria. Data were extracted and analysed using descriptive content analysis.</p><p><strong>Results: </strong>Sixteen systematic reviews, two scoping reviews and five good quality cohort studies were included. 'Nature' was conceptualised along a continuum (the 'nature research framework') into three categories: a human-designed environment with natural elements; a human-designed natural environment; and a natural environment. The nature 'intervention' falls into three areas (the 'nature intervention framework'): access, exposure and engagement with nature, with quantity and quality of nature relevant to all areas. Mental health and well-being outcomes fit along a continuum, with 'disorder' at one end and 'well-being' at the other. Nature appears to have a beneficial effect, but we cannot be certain of this.</p><p><strong>Conclusions: </strong>Nature appears to have a beneficial effect on mental health and well-being of children and adolescents. Evidence is lacking on clinical populations, ethnically diverse populations and populations in low- and middle-income countries. Our results should be interpreted considering the limitations of the included studies and confidence in findings.</p>","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":" ","pages":"401-409"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"British contributions to the therapeutic use of John Cade's lithium.","authors":"Gin S Malhi, Erica Bell","doi":"10.1192/bjp.2024.155","DOIUrl":"10.1192/bjp.2024.155","url":null,"abstract":"<p><p>Coinciding with the 75th anniversary of John Cade's seminal publication that first reported lithium's antimanic efficacy, we briefly recount the salient findings of the historic paper and draw attention to the important psychiatric research in Britain that reinforced its findings and the critical British opinions that likely impeded its clinical use.</p>","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":" ","pages":"353-356"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Equanimity in psychiatric medicine: the mind in the middle - Psychiatry in history.","authors":"Michael Uebel","doi":"10.1192/bjp.2024.63","DOIUrl":"https://doi.org/10.1192/bjp.2024.63","url":null,"abstract":"","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":"225 3","pages":"413"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study: commentary, Fazel.","authors":"Seena Fazel","doi":"10.1192/bjp.2024.59","DOIUrl":"https://doi.org/10.1192/bjp.2024.59","url":null,"abstract":"","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":"225 3","pages":"411"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sensitivity to light in bipolar disorder: implications for research and clinical practice: commentary, Terao.","authors":"Takeshi Terao","doi":"10.1192/bjp.2024.54","DOIUrl":"https://doi.org/10.1192/bjp.2024.54","url":null,"abstract":"","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":"225 3","pages":"410"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saeed Farooq, Miriam Hattle, Tom Kingstone, Olesya Ajnakina, Paola Dazzan, Arsime Demjaha, Robin M Murray, Marta Di Forti, Peter B Jones, Gillian A Doody, David Shiers, Gabrielle Andrews, Abbie Milner, Maria Antonietta Nettis, Andrew J Lawrence, Danielle A van der Windt, Richard D Riley
{"title":"Development and initial evaluation of a clinical prediction model for risk of treatment resistance in first-episode psychosis: Schizophrenia Prediction of Resistance to Treatment (SPIRIT).","authors":"Saeed Farooq, Miriam Hattle, Tom Kingstone, Olesya Ajnakina, Paola Dazzan, Arsime Demjaha, Robin M Murray, Marta Di Forti, Peter B Jones, Gillian A Doody, David Shiers, Gabrielle Andrews, Abbie Milner, Maria Antonietta Nettis, Andrew J Lawrence, Danielle A van der Windt, Richard D Riley","doi":"10.1192/bjp.2024.101","DOIUrl":"10.1192/bjp.2024.101","url":null,"abstract":"<p><strong>Background: </strong>A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication.</p><p><strong>Aims: </strong>To develop and evaluate a model that could predict the risk of TRS in routine clinical practice.</p><p><strong>Method: </strong>We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis. Using sociodemographic and clinical predictors, a model for predicting risk of TRS was developed based on penalised logistic regression, with missing data handled using multiple imputation. Internal validation was undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. Interviews and focus groups with clinicians were conducted to establish clinically relevant risk thresholds and understand the acceptability and perceived utility of the model.</p><p><strong>Results: </strong>We included seven factors in the prediction model that are predominantly assessed in clinical practice in patients with FEP. The model predicted treatment resistance among the 1081 patients with reasonable accuracy; the model's C-statistic was 0.727 (95% CI 0.723-0.732) prior to shrinkage and 0.687 after adjustment for optimism. Calibration was good (expected/observed ratio: 0.999; calibration-in-the-large: 0.000584) after adjustment for optimism.</p><p><strong>Conclusions: </strong>We developed and internally validated a prediction model with reasonably good predictive metrics. Clinicians, patients and carers were involved in the development process. External validation of the tool is needed followed by co-design methodology to support implementation in early intervention services.</p>","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":" ","pages":"379-388"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ann John, Olivier Y Rouquette, Sze Chim Lee, Jo Smith, Marcos Del Pozo Baños
{"title":"Trends in incidence of self-harm, neurodevelopmental and mental health conditions among university students compared with the general population: nationwide electronic data linkage study in Wales.","authors":"Ann John, Olivier Y Rouquette, Sze Chim Lee, Jo Smith, Marcos Del Pozo Baños","doi":"10.1192/bjp.2024.90","DOIUrl":"10.1192/bjp.2024.90","url":null,"abstract":"<p><strong>Background: </strong>Concern that self-harm and mental health conditions are increasing in university students may reflect widening access to higher education, existing population trends and/or stressors associated with this setting.</p><p><strong>Aims: </strong>To compare population-level data on self-harm, neurodevelopmental and mental health conditions between university students and non-students with similar characteristics before and during enrolment.</p><p><strong>Method: </strong>This cohort study linked electronic records from the Higher Education Statistics Agency for 2012-2018 to primary and secondary healthcare records. Students were undergraduates aged 18 to 24 years at university entry. Non-students were pseudo-randomly selected based on an equivalent age distribution. Logistic regressions were used to calculate odds ratios. Poisson regressions were used to calculate incidence rate ratios (IRR).</p><p><strong>Results: </strong>The study included 96 760 students and 151 795 non-students. Being male, self-harm and mental health conditions recorded before university entry, and higher deprivation levels, resulted in lower odds of becoming a student and higher odds of drop-out from university. IRRs for self-harm, depression, anxiety, autism spectrum disorder (ASD), drug use and schizophrenia were lower for students. IRRs for self-harm, depression, attention-deficit hyperactivity disorder, ASD, alcohol use and schizophrenia increased more in students than in non-students over time. Older students experienced greater risk of self-harm and mental health conditions, whereas younger students were more at risk of alcohol use than non-student counterparts.</p><p><strong>Conclusions: </strong>Mental health conditions in students are common and diverse. While at university, students require person-centred stepped care, integrated with local third-sector and healthcare services to address specific conditions.</p>","PeriodicalId":9259,"journal":{"name":"British Journal of Psychiatry","volume":" ","pages":"389-400"},"PeriodicalIF":8.7,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}