TY - JOUR

T1 - Regional differences in mortality risk and in attenuating or aggravating factors in schizophrenia

T2 - A systematic review and meta-analysis

AU - Solmi, Marco

AU - Croatto, Giovanni

AU - Fornaro, Michele

AU - Schneider, Lynne Kolton

AU - Rohani-Montez, S. Christy

AU - Fairley, Leanne

AU - Smith, Nathalie

AU - Bitter, István

AU - Gorwood, Philip

AU - Taipale, Heidi

AU - Tiihonen, Jari

AU - Cortese, Samuele

AU - Dragioti, Elena

AU - Rietz, Ebba Du

AU - Nielsen, Rene Ernst

AU - Firth, Joseph

AU - Fusar-Poli, Paolo

AU - Hartman, Catharina

AU - Holt, Richard I.G.

AU - Høye, Anne

AU - Koyanagi, Ai

AU - Larsson, Henrik

AU - Lehto, Kelli

AU - Lindgren, Peter

AU - Manchia, Mirko

AU - Nordentoft, Merete

AU - Skonieczna-Żydecka, Karolina

AU - Stubbs, Brendon

AU - Vancampfort, Davy

AU - Boyer, Laurent

AU - De Prisco, Michele

AU - Vieta, Eduard

AU - Correll, Christoph U.

AU - ECNP Physical And meNtal Health Thematic Working Group (PAN-Health)

N1 - Publisher Copyright: © 2023

PY - 2024

Y1 - 2024

N2 - People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09–8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92–2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08–18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07–4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.

AB - People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09–8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92–2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08–18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07–4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.

KW - Antipsychotic

KW - Geographical regions

KW - Meta-analysis

KW - Mortality

KW - Schizophrenia

KW - Systematic review

U2 - 10.1016/j.euroneuro.2023.12.010

DO - 10.1016/j.euroneuro.2023.12.010

M3 - Review

C2 - 38368796

AN - SCOPUS:85185587037

VL - 80

SP - 55

EP - 69

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -