Treatment-resistant depression and risk of all-cause mortality and suicidality in Danish patients with major depression

Objective: Treatment-resistant depression (TRD) has been associated with higher mortality and risk of suicide, but this has mainly been showed in few studies which did not include self-harm. The aim was to investigate the association of TRD with all-cause mortality, suicide and self-harm in a nationwide cohort of patients with major depression and explore any differences in relation to patient characteristics. Methods: First-time hospital contacts for major depression between January 1, 1996 and December 31, 2014 were identified in Danish patient registers (ICD-10: F32 and F33). TRD was defined as two shifts in antidepressant treatment, assessed from one year prior depression diagnosis until one year after. Information on mortality, suicide and self-harm was obtained from Danish registers and associations between TRD and the three prognostic outcomes were analyzed using Cox Proportional Hazard Regression. Results: TRD was not associated with all-cause mortality the first year of follow-up (adjusted HR (aHR) 1.04, 95% confidence interval (CI) [0.98–1.11]), and the HR for mortality was lower the following 1–5 years. However, TRD was associated with higher rates of suicide (0–1 year: aHR 2.20, 95% CI [1.77–2.74]; 1–5 years: aHR 1.70, 95% CI [1.42–2.03]) and self-harming behavior (0–1 year: aHR 1.51, 95% CI [1.36–1.66]; 1–5 years: aHR 1.59, 95% CI [1.48–1.70]). The above risk estimates varied only slightly across sociodemographic and clinical patient characteristics. Conclusions: Patients with TRD have higher rates of suicide and self-harm compared with non-TRD patients, whereas there seems to be no increase overall in all-cause mortality – in fact, there was a lower rate at follow-up after 1 year. We found only a few differences in HRs for mortality or suicidality across patient characteristics.