Excess mortality and life-years lost in people diagnosed with depression: A 20-year population-based cohort study of 126,573 depressed individuals followed for 1,139,073 persons-years

Depression is associated with premature mortality, but evidence is mainly derived from Western countries. Very limited research has evaluated shortened lifespan in depression using life-years-lost (LYLs), a recently developed mortality metric taking into account the illness onset for life expectancy estimation. Temporal trends of differential mortality gap are understudied. This population-based cohort study, which utilized a territory-wide medical-record database of public inpatient and outpatient healthcare services in Hong Kong, evaluated the extent of premature mortality in 126,573 individuals with depression (persons-years=1,139,073) between January 2002 and December 2021 regarding the standardized mortality ratio (SMR) and excess LYLs. Trends in annual SMRs over 20 years were assessed by joinpoint analyses. The results showed that individuals with depression exhibited significantly higher all-cause (SMR=1.84 [95% CI=1.82-1.88]), natural-cause (1.69 [1.66-1.72]), and unnatural-cause (5.24 [4.97-5.51]) mortality rates than the general population. Suicidespecific SMR was markedly elevated (7.92 [7.47-8.38]), particularly in the 15-34 year-olds (12.75 [10.87-14.79]). Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Excess LYLs extended to men (5.67 years, 95% CI = 5.45-5.90) and women (4.06 years, 95% CI = 3.89-4.23). Overall and natural-cause mortality rates improved over time, but unnatural-cause and suicide-related mortality gaps persisted. Taken together, this study indicates that depression is associated with increased premature mortality and reduced lifespan in a predominantly Chinese population, mainly attributed to natural causes. Relative suicide-specific mortality is substantially elevated, especially among young people. The pronounced mortality gap underscores an urgent need for effective interventions targeting improved physical health and suicide risk reduction in individuals with depression.