Sex-stratified mortality estimates in people with schizophrenia: A systematic review and meta-analysis of cohort studies of 2,700,825 people with schizophrenia

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. Weconducted a PRISMA 2020-compliant systematic review and random-effects metaanalysis 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. There were minimal statistically significant differences in sex-dependent mortality risks in people with schizophrenia. However, it revealed areas of targeted intervention efforts.