BACKGROUND: Mental disorders are associated with excess risk of death from unnatural and natural causes, but few studies have differentiated causes of death among patients with major depression. We examined cumulative and relative risks of all-cause and cause-specific mortality in individuals with major depression up to 50 years after diagnosis according to sex, age, and time since depression diagnosis. METHODS: In this nationwide matched-cohort study, we included individuals diagnosed with major depression in Danish National Patient registries from 1970 through 2021 and a 1:5 matched sample of the general population (reference population). Individuals were followed for their underlying cause of death in the Danish Cause of Death Registry up to 2022, and we estimated cumulative risk and hazard ratios for all-cause and 10 specific causes of death. RESULTS: The study included 330,577 adults diagnosed with major depression in Denmark (median age at first diagnosis, 45 years
63.4%women) and 1,652,885 members of the matched reference population (median age, 45 years
63.4%women). During the study period, 116,628 (35.2%) individuals with depression and 389,135 (23.5%) matches from the reference population died. Individuals with depression had considerably higher mortality risk at all time periods and ages compared to the reference population, and the increased risk was most pronounced in the first year after diagnosis. The lifetime risk of suicide was 11.2% in individuals with depression compared with 1% in the reference population, and before age 65 years, suicide was the leading cause of death in patients with depression. When compared with the reference population, individuals with depression also exhibited a higher risk of various specific natural causes of death before the age of 85 years. CONCLUSIONS: The risk of death from suicide and medical disorders is elevated in individuals with depression, especially the first year after diagnosis. Because a large number of deaths can be attributed to depression shortly after onset, clinicians should be aware of this risk.