Objective: Depression is associated with excess mortality, but it is not yet known how treatment-resistance influences life expectancy. This study estimates all-cause and cause-specific mortality rate ratios (MRR) and excess Life Years Lost (LYL) in individuals with treatment-resistant depression (TRD) first identified in primary care.
Methods: All individuals born and living in Denmark who filled their first prescription for an antidepressant drug at age 18-69 years between 1996 and 2012 were identified in the Danish National Prescription Registry (N=562,648). Individuals with at least two additional different treatment trials within three years were classified as TRD. MRRs were estimated with Cox Proportional Hazards regression adjusted for age at first prescription, calendar year and comorbidity, and LYL by the Life Years Lost method.
Results: Of the population, 27,920 (5%) individuals were identified with TRD. The study cohort was observed over 5,863,165 person-years (TRD: 278,002), in which there were 71,374 deaths (TRD: 2,901).
Individuals with TRD had a significant excess mortality compared to individuals who respond to treatment.
Adjusted MRRs between individuals with and without TRD was highest for suicide and accidents in both men (aMRR: 3.13, 95% CI 2.67; 3.66 and aMRR: 1.30, 95% CI 1.03; 1.65) and women (aMRR: 6.06, 95% CI 5.08; 7.23 and aMRR: 1.67, 95% CI 1.26; 1.65). Correspondingly, for men, diseases of the circulatory system, suicide, alcohol misuse and accidents accounted for the major shares of life-years lost in individuals with TRD, while for women, it was suicide, respiratory diseases and accidents.
Conclusions: This is the first study to investigate excess mortality in individuals with TRD first identified in primary care and our findings emphasize the need for prevention of suicide in individuals with depression when they do not respond adequately to treatment.