Abstract: The differential influence of sex on premature mortality in schizophrenia is unclear. This study assessed the differences in all-cause and specific cause mortality risks in people with schizophrenia compared to several control groups stratified by sex. We conducted a PRISMA 2020-compliant systematic review and random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) for people with schizophrenia, comparing by sex. We measured publication bias and conducted a quality assessment through the Newcastle-Ottawa scale. We meta-analyzed 43 studies reporting on 2,700,825 people with schizophrenia. Both males and females with schizophrenia had increased all-cause mortality vs. comparison groups (males, RR=2.62, 95%CI 2.35-2.92; females, RR=2.56, 95%CI 2.27-2.87), suicide (males, RR=9.02, 95%CI 5.96-13.67; females, RR=12.09, 95%CI 9.00-16.25), and natural cause mortality (males, RR=2.11, 95%CI 1.88-2.38; females, RR=2.14, 95%CI 1.93-2.38). No statistically significant differences in sex-dependent mortality risk emerged. There was an age-group-dependent increased mortality risk in females < 40 years vs. >/=40 years old (RR=4.23/2.17), and significantly higher risk of death due to neurological disorders (dementia) in males vs. females (RR=5.19/2.40). Increased mortality risks were often associated with specific modifiable risk factors. The increased mortality risk did not improve over time, calling for more studies to identify modifiable factors, and for better physical healthcare for males and females with schizophrenia.
Competing Interests: Declaration of competing interest Disclosures MS received honoraria/has been a consultant for AbbVie, Angelini, Lundbeck, Otsuka. IB received consulting fees from Gedeon Richter and Janssen/Janssen-Cilag; speaker's honoraria from Gedeon Richter, Hikma Pharmaceuticals, Janssen/Janssen-Cilag, KRKA, Lundbeck and Medichem Pharmaceuticals Inc. by Unilab; received research grant from Gedeon Richter; royalties from Oxford University Press. JT has participated in research projects funded by grants from Janssen-Cilag to his employing institution; he has been a consultant to HLS Therapeutics, Janssen, Orion, Teva, and WebMed Global and received lecture fees from Janssen, Lundbeck and Otsuka. PG received during the last 5 years fees for presentations at congresses or participation in scientific boards from Biogen, Janssen, Lundbeck, Merk, Otsuka, Richter and Viatris. R.E.N. has, within the past 3 years, been an investigator for Compass Pharmaceuticals, Janssen-Cilag, Sage and Boehringer-Ingelheim for clinical trials; has received speaking fees from Lundbeck, Teva Pharmaceuticals, Janssen-Cilag and Otsuka Pharmaceuticals; and has acted as advisor to Lundbeck and Janssen-Cilag. JF is supported by a UK Research and Innovation Future Leaders Fellowship (MR/T021780/1) and has received honoraria / consultancy fees from Atheneum, Informa, Gillian Kenny Associates, Bayer, Big Health, Hedonia, Strive Coaching, Wood For Trees, Nutritional Medicine Institute, Angelini, ParachuteBH, Richmond Foundation and Nirakara, independent of this work. RIGH has received fees for lecturing from Boehringer-Ingelheim, EASD, Eli Lilly, Encore, Liberum, Novo Nordisk, ROVI and funding for conference attendance from Novo Nordisk and Eli Lilly. HT has participated in research projects funded by grants from Janssen-Cilag to her employing institution; and she has received lecture fees from Gedeon Richter, Janssen, Lundbeck and Otsuka. MF received honoraria for his speaker activity from the American Society of Clinical Psychopharmacology (ASCP) and served as a consultant for Angelini, Otsuka, Lundbeck, Sanofi-Aventis, and Boehringer Ingelheim. BS is on the Editorial Board of Ageing Research Reviews, Mental Health and Physical Activity, The Journal of Evidence Based Medicine, and The Brazilian Journal of Psychiatry. Brendon has received honorarium from a co-edited book on exercise and mental illness (Elsevier), and unrelated advisory work from ASICS, in addition to honorarium and stock options at FitXR LTD. HL reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals and Evolan Pharma AB; all outside the submitted work. Henrik Larsson is editor-in-chief of JCPP Advances. CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Adock Ingram, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Bristol-Meyers Squibb, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Maplight, Mylan, Neumora Therapeutics, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Tolmar, Vertex, Viatris and Xenon Pharmaceuticals. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic. PL reports institutional grants from AstraZeneca, Biogen, Jansen, MSD and Novartis. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Beckley-Psytech, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris, outside the submitted work. MH has recieved honoraria for consultancy and/or speaking from Lundbeck and Otsuka.
(Copyright © 2024. Published by Elsevier B.V.)
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