Objectives: Depression is the second most prevalent mental illness among the elderly. Nonetheless, treatment- resistant depression (TRD) is prevalent among the elderly; one-third of elderly patients with major depressive disorder (MDD) who received antidepressant treatment failed to achieve remission. Although there have been several studies regarding the associations between MDD and increased mortality and suicidal risk, studies between TRD and mortality/suicidal risk in the elderly still remains limited. In this national cohort study, we examined the association between TRD, non-TRD MDD, and non-depression with all-cause mortality, accident mortality, and suicide mortality.

Methods: For this retrospective longitudinal analysis on the entire population, the National Health Insurance Research Database of Taiwan, which comprises claims data from a lifetime insurance program and provided comprehensive medical inpatient and outpatient information categorized by ICD-9-CM and ICD-10. The National Mortality Registry offered information regarding mortality resulting from all causes, natural causes, suicide, and accidents. A cohort of ≥60-year-old patients, including both those with and without MDD, was observed between January 2003 and December 2017. Individuals were classified as TRD if they had undergone aminimum of two distinct antidepressant trials within the current episode’s two-year duration and dose, as documented in the prescribing records. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated for mortality risk utilizing Cox regression models.

Results: Among those >60 years old, after adjusting with sex and comorbidities, TRD was associated with increased risk of suicide (aHR 7.4, 95% CI [5.6-9.8]; MDD without TRD 4.4 [4.1- 4.6], compared with non-MDD group). Simliar risk of accident mortality was observed among three groups (TRD aHR 1.3 [0.9-1.9]; MDD without TRD 0.9 [0.9-1.0], compared with non-MDD group). Surprisely, TRD might presented lower mortality risk of natural mortality than the non- MDD group (TRD aHR 0.8 [0.7-0.8]; MDD without TRD 0.9 [0.8-0.9], compared with non- MDD group).

Conclusions: The suicide mortality among elderly patients with TRD is higher in comparison to non-MDD patients; nevertheless, accident mortality does not appear to have increased and the natural mortality rate is reduced. The lower mortality may reflect patient selection, and the contributing factors need further evaluation.