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Background: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. Methods: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Findings: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94–1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ 2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. Interpretation: We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. Funding: Lundbeck and Otsuka.

Made available in DSpace on 2022-04-28T19:40:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 Background: The COVID-19 pandemic is having profound mental health consequences for many people. Concerns have been expressed that, at their most extreme, these consequences could manifest as increased suicide rates. We aimed to assess the early effect of the COVID-19 pandemic on suicide rates around the world. Methods: We sourced real-time suicide data from countries or areas within countries through a systematic internet search and recourse to our networks and the published literature. Between Sept 1 and Nov 1, 2020, we searched the official websites of these countries’ ministries of health, police agencies, and government-run statistics agencies or equivalents, using the translated search terms “suicide” and “cause of death”, before broadening the search in an attempt to identify data through other public sources. Data were included from a given country or area if they came from an official government source and were available at a monthly level from at least Jan 1, 2019, to July 31, 2020. Our internet searches were restricted to countries with more than 3 million residents for pragmatic reasons, but we relaxed this rule for countries identified through the literature and our networks. Areas within countries could also be included with populations of less than 3 million. We used an interrupted time-series analysis to model the trend in monthly suicides before COVID-19 (from at least Jan 1, 2019, to March 31, 2020) in each country or area within a country, comparing the expected number of suicides derived from the model with the observed number of suicides in the early months of the pandemic (from April 1 to July 31, 2020, in the primary analysis). Findings: We sourced data from 21 countries (16 high-income and five upper-middle-income countries), including whole-country data in ten countries and data for various areas in 11 countries). Rate ratios (RRs) and 95% CIs based on the observed versus expected numbers of suicides showed no evidence of a significant increase in risk of suicide since the pandemic began in any country or area. There was statistical evidence of a decrease in suicide compared with the expected number in 12 countries or areas: New South Wales, Australia (RR 0·81 [95% CI 0·72–0·91]); Alberta, Canada (0·80 [0·68–0·93]); British Columbia, Canada (0·76 [0·66–0·87]); Chile (0·85 [0·78–0·94]); Leipzig, Germany (0·49 [0·32–0·74]); Japan (0·94 [0·91–0·96]); New Zealand (0·79 [0·68–0·91]); South Korea (0·94 [0·92–0·97]); California, USA (0·90 [0·85–0·95]); Illinois (Cook County), USA (0·79 [0·67–0·93]); Texas (four counties), USA (0·82 [0·68–0·98]); and Ecuador (0·74 [0·67–0·82]). Interpretation: This is the first study to examine suicides occurring in the context of the COVID-19 pandemic in multiple countries. In high-income and upper-middle-income countries, suicide numbers have remained largely unchanged or declined in the early months of the pandemic compared with the expected levels based on the pre-pandemic period. We need to remain vigilant and be poised to respond if the situation changes as the longer-term mental health and economic effects of the pandemic unfold. Funding: None. Centre for Mental Health Melbourne School of Population and Global Health University of Melbourne Swansea University Medical School Translational Health Research Institute Western Sydney University Ministry of Public Health Department of Health Promotion National Confidential Inquiry into Suicide and Safety in Mental Health University of Manchester Centre for Mental Health and Safety and National Institute for Health Research Patient Safety Translational Research Centre University of Manchester School of Public Health National Suicide Research Foundation University College Cork Australian Institute for Suicide Research and Prevention School of Applied Psychology Griffith University Institute for Life Course Health Research Department of Global Health Stellenbosch University Working Group on Prevention of Suicide and Depression at Public Health Council Department of Psychiatry Blekinge Hospital Botucatu Medical School Universidade Estadual Paulista Instituto Nacional de Psiquiatría Ramon de la Fuente Muñiz University of Rochester Medical Center Region Friuli Venezia Giulia Central Health Directorate Outpatient and Inpatient Care Service Department of Medicine University of Udine Institute of Health Behaviors and Community Sciences College of Public Health National Taiwan University Thames Valley Local Criminal Justice Board Department of Psychiatry Psychotherapy and Psychosomatics Medical University of Innsbruck Center for Outcomes Research and Evaluation Yale School of Medicine Coroners Court of Victoria Danish Research Institute for Suicide Prevention Department of Mental Health Johns Hopkins School of Public Health Centre for Mental Health Research Australian National University Brigham and Women's Hospital Department of Emergency Medicine School of Population Health University of Auckland Magistrates Court of Tasmania (Coronial Division) Bureau of Vital Records and Statistics Louisiana Office of Public Health Ministry of Public Health Undersecretary of Health Services Research Department, 113 Suicide Prevention Departments of Psychiatry and Epidemiology Columbia University Medical Center/New York State Psychiatric Institute Centre for Suicide Research University of Oxford Louisiana Department of Health Greater Manchester Mental Health NHS Foundation Trust Department of Psychiatry Aga Khan University KU Leuven Center for Contextual Psychiatry Population Health Sciences Bristol Medical School University of Bristol South Asian Clinical Toxicology Research Collaboration Faculty of Medicine University of Peradeniya World Health Organization Country Office for Nepal Karolinska Institutet Bekhterev National Medical Research Center of Psychiatry and Neurology Pavlov First Saint Petersburg State Medical University Unit Suicide Research and Mental Health Promotion Department of Social and Preventive Medicine Center for Public Health Medical University of Vienna Department of Child and Adolescent Psychiatry Medical University of Vienna School of Psychology University of Nottingham Self-Harm Research Group School of Psychology University of Nottingham Mental Health Centre Copenhagen Department of Psychiatry and Psychotherapy Klinikum Klagenfurt am Wörthersee Suicidal Behaviour Research Lab University of Glasgow Preventing Deaths from Poisoning Research Group University of Edinburgh Usher Institute University of Edinburgh Suicide Research and Prevention Center Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Departments of Psychiatry and Epidemiology Columbia University Department of Child and Adolescent Psychiatry and Psychotherapy University of Ulm Psychosocial Services in Vienna National Centre for Suicide Research and Prevention Institute of Clinical Medicine University of Oslo Department of Child and Adolescent Psychiatry Psychotherapy and Psychosomatics University Hospital Leipzig Department of Psychiatry and Psychotherapeutic Medicine Landeskrankenhaus Villach Department of Psychiatry Psychosomatic Medicine and Psychotherapy University Hospital Frankfurt Department of Borderline Disorders and Psychotherapy Bekhterev National Medical Research Center of Psychiatry and Neurology Saint Petersburg State University Department of Psychiatry Health Authority Frankfurt am Main Department of Addictive Disorders Psychiatry and Psychotherapy LVR-Klinik Köln Department of Psychiatry Psychosomatic Medicine and Psychotherapy Goethe-University Organizational-Scientific Department Bekhterev National Medical Research Center of Psychiatry and Neurology Department of Psychiatry University of Toronto Department of Psychiatry Sunnybrook Health Sciences Centre Waseda University Faculty of Political Science and Economics Sneha—Suicide Prevention Centre Voluntary Health Services Department of Community Medicine Faculty of Medicine and Allied Sciences Rajarata University of Sri Lanka Department of Psychiatry Sackler School of Medicine Tel Aviv University and Geha Mental Health Center Division of Molecular Imaging and Neuropathology New York State Psychiatric Institute and Department of Psychiatry Columbia University National Institute of Health Research Biomedical Research Centre University Hospitals Bristol and Weston NHS Foundation Trust University of Bristol Department for Psychiatry University Psychiatric Hospital Vrapče School of Medicine University of Zagreb Botucatu Medical School Universidade Estadual Paulista