Cause-specific mortality due to physical illness in severe mental disorders in Europe: a population-based multi-country cohort study

Background: How specific physical illnesses differentially contribute to the persistent mortality gap in severe mental illness (including schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder) remains poorly understood. Using a harmonised multi-country design, we aimed to analyse excess mortality across diagnoses and causes of death to identify high-burden and high-inequity mortality patterns to inform public health prioritisation and organisation of care. Methods: In this population-based multi-country cohort study using national health registers, we identified people diagnosed with severe mental illness at age 15-65 years in five European countries (Denmark, Finland, France, Poland, and Sweden) during 2004-23 to establish excess mortality before age 75 years in relation to country-specific general population mortality. We defined cause-specific mortality using ICD-10. Random effects meta-analysis was used to pool mortality estimates representing country-specific relative mortality inequities (sex-standardised and age-standardised mortality ratios), absolute excess burden (sex-standardised and age-standardised death rates per 10 000 person-years), and the severity of premature mortality (potential years-of-life-lost before age 75 years). Subgroup analyses were conducted to test for potential effect modification. Findings: Between Jan 1, 2004, and Dec 31, 2023, there were 4 861 795 people with severe mental illness, and 561 903 deaths from any cause. All-cause mortality was 2·6-fold higher in people with severe mental illness compared with the general population (pooled standardised mortality ratio [SMR] 2·64, 95% CI 2·25-3·11). Absolute excess mortality was highest in cardiovascular disease (schizophrenia spectrum disorders: standardised excess death rate 22·08 per 10 000 person-years, 95% CI 8·77-35·39; bipolar disorder: 8·36 per 10 000 person-years, 2·96-13·75; and major depressive disorder: 9·82 per 10 000 person-years, 3·18-16·45). Relative excess mortality was highest in respiratory diseases (schizophrenia spectrum disorders: SMR 6·49; 95% CI 5·52-7·64; bipolar disorder: 2·72, 2·04-3·63; and major depressive disorder: 3·48, 2·63-4·62), followed by endocrine and metabolic diseases (schizophrenia spectrum disorders: 5·09, 4·29-6·04; bipolar disorder: 2·60, 2·26-2·98; and major depressive disorder: 3·07, 1·84-5·12), and in gastrointestinal diseases (schizophrenia spectrum disorders: 3·47, 2·58-4·67; bipolar disorder: 2·34, 2·00-2·74; and major depressive disorder: 3·48, 2·63-4·62). Interpretation: The mortality gap was characterised by distinct patterns of absolute excess mortality and relative inequality across causes of death and severe mental illness diagnoses. Considering both dimensions of excess mortality can inform public health priorities that are not apparent from either measure alone or from focusing on cause-specific numbers of deaths. Reducing premature mortality will therefore require an integrated public health approach that combines universal strategies with targeted interventions to address both high-burden causes of death and those characterised by the greatest relative inequalities. Funding: 2024 European Partnership on Transforming Health and Care Systems.