Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden

Abstract Background The impact of treatment resistant depression (TRD) on mortality is not established. Methods Using Swedish national registers, 118,774 patients between 18–69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). Results In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21–1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69–2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31–1.76), highest among patients 18–29 years old (EMRR 2.03; 1.31–1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63–2.43). Limitations Severity of depression and adherence to treatment were not available in the data. Conclusions Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.