All-cause and cause-specific mortality risk in individuals with eating disorders: systematic review and meta-analysis of relative risk and aggravating or attenuating factors

Previous meta-analyses estimating mortality risk in eating disorders (EDs) were restricted to specific disorders or causes of death, and were published before the release of the DSM-5, which introduced significant changes in ED classification. We conducted a PRISMA 2020-compliant systematic review and random-effects meta-analysis assessing all-cause (primary outcome) and cause-specific mortality risk ratio (RR) in cohort/case-control studies of individuals with EDs versus the general population or groups matched by physical and/or psychiatric comorbidities. Meta-regression/subgroup analyses assessed risk aggravating or attenuating factors. Study quality was evaluated using design-specific US National Institutes of Health tools. Altogether, 83 studies were meta-analyzed (patients with EDs: N=307,710, general population controls: N=15,719,076; mean follow-up: 11.96 years, females: 94.35%, mean age: 25.52 years). The quality was rated as “good” in 65.0%, “fair” in 21.7%, and “poor” in 13.3% of the studies. Any ED was associated with higher all-cause mortality vs. the general population (RR=4.92, 95% CI: 4.03-6.00, ranging from RR=5.52, 95% CI: 4.47-6.82 in anorexia nervosa (AN) to non-significant difference in binge eating disorder), as well as with higher suicide-related mortality (RR=8.45, 95% CI: 5.73-12.47, ranging from RR=9.86, 95% CI: 5.63-17.27 in AN to RR=6.15, 95% CI: 2.52-15.04 in bulimia nervosa). Mortality risk from both natural and non-natural causes was also increased in individuals with EDs vs. the general population (RR=3.47, 95% CI: 2.29-5.25, and RR=6.46, 95% CI: 4.62-9.04, respectively). All-cause mortality increased with lower body mass index and shorter follow-ups. Male sex, any psychiatric comorbidity, and comorbid substance use, alcohol use, mood or personality disorders were significantly associated with higher all-cause mortality risk in any ED. These data confirm that EDs are associated with a high all-cause, suicide-related and other cause-specific mortality risk, and indicate that monitoring of physical and psychiatric complications and suicide risk early after diagnosis, particularly in AN, males and individuals with low body mass index, is absolutely needed. Further research is warranted to identify actionable factors that can reduce ED-associated mortality risk.