Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia: A subanalysis of a systematic review and meta-analysis with meta-regression of moderators.

Lynne Kolton Schneider, Richard I G Holt, Henrik Larsson, Davy Vancampfort, Eduard Vieta, Christoph U Correll, Karolina Skonieczna-Żydecka, Brendon Stubbs, István Bitter, Laurent Boyer, S Christy Rohani-Montez, Leanne Fairley, Nathalie Smith, Heidi Taipale, Ebba Du Rietz, Rene Ernst Nielsen, Anne Høye, Kelli Lehto, Paolo Fusar-Poli, Catharina Hartman, Jari Tiihonen, Peter Lindgren, Merete Nordentoft, Arnav Gupta, Elena Dragioti, Stanley Wong, Nicholas Fabiano, Michele De Prisco, Samuele Cortese, Giovanni Croatto, Philip Gorwood, Michele Fornaro, Joseph Firth, Ai Koyanagi, Marco Solmi, Mirko Manchia

Journal: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 2024;88():6-20

PMID: 39121717

Free Full Text on Elsevier Science View on PubMed

Abstract

To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29-3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20-2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.

Address: Department of Psychiatry, University of Ottawa, 501 Smyth Road, Ottawa, ON, Canada; Department of Mental Health, The Ottawa Hospital, Ottawa, Canada; Ottawa Hospital Research Institute: Clinical Epidemiology Program, University of Ottawa, Ottawa, Canada; School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; SCIENCES Lab, Department of Psychiatry, University of Ottawa, Ottawa, Canada. Electronic address: [email protected].; Mental Health Department, AULSS 3 Serenissima, Mestre, Venice, Italy.; Department of Medicine, University of Calgary, Calgary, Canada; College of Public Health, Kent State University, Kent, United States.; Department of Psychiatry, University of Ottawa, 501 Smyth Road, Ottawa, ON, Canada; SCIENCES Lab, Department of Psychiatry, University of Ottawa, Ottawa, Canada.; SCIENCES Lab, Department of Psychiatry, University of Ottawa, Ottawa, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.; Section of Psychiatry, Department of Neuroscience, Reproductive Science, and Dentistry, Federico II University of Naples, Naples, Italy.; WebMD Global LLC, London, United Kingdom.; Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.; Université Paris Cité, INSERM U1266, Institute of Psychiatry and Neurosciences of Paris (IPNP), Paris, France; GHU Paris Psychiatrie et Neurosciences (CMME, Sainte-Anne Hospital), Paris, France.; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; School of Pharmacy, University of Eastern Finland, Kuopio, Finland.; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland.; Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom; Solent NHS Trust, Southampton, United Kingdom; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York, NY, United States; DiMePRe-J-Department of Precision and Regenerative Medicine-Jonic Area, University of Bari "Aldo Moro", Bari, Italy.; Pain and Rehabilitation Centre, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Research Laboratory Psychology of Patients, Families, and Health Professionals, Department of Nursing, School of Health Sciences, University of Ioannina, Ioannina, Greece.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark.; Division of Psychology and Mental Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom.; Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Outreach and Support in South-London (OASIS) service, South London and Maudlsey (SLaM) NHS Foundation Trust, United Kingdom; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilian-University (LMU), Munich, Germany.; Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.; Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.; Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, ISCIII, Dr. Antoni Pujadas, 42, Sant Boi de Llobregat, Barcelona 08830, Spain; ICREA, Pg. Lluis Companys 23, Barcelona 08010, Spain.; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.; Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden; The Swedish Institute for Health Economics, Lund, Sweden.; Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; Unit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, Italy; Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.; Mental Health Centre Copenhagen, Department of Clinical Medicine, Copenhagen University Hospital, Denmark.; Department of Biochemical Science, Pomeranian Medical University in Szczecin, Szczecin 71-460, Poland.; Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom.; Department of Rehabilitation Sciences, KU Leuven, Leuven, Belgium; University Psychiatric Centre KU Leuven, Kortenberg, Leuven, Belgium.; Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.; AP-HM, Aix-Marseille University, School of medicine - La Timone Medical Campus, UR3279: Health Service Research and Quality of Life Center (CEReSS), Marseille, France.; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, United States; Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.

DOI: 10.1016/j.euroneuro.2024.07.009