Treatment-Resistant Depression Associated With Increased Risk for Mortality

sad boy sitting in corner
sad boy sitting in corner
Investigators examined mortality in patients with treatment-resistant depression compared with non-treatment resistant depression.

A study recently published in the Journal of Affective Disorders has found that patients with treatment-resistant depression had a higher risk for mortality due to external causes than those with non-treatment-resistant depression. Individuals who are relatively young and healthy are at the highest risk. 

This study included 118,774 individuals diagnosed with depression and prescribed antidepressants. Of the total participants, were 15,013 patients diagnosed with treatment-resistant depression.  Patients with treatment-resistant depression had a 35% higher all-cause mortality (hazard ratio [HR] 1.35; 95% CI, 1.21-1.50) compared with the non-treatment-resistant depression group.  Those with treatment-resistant depression experienced higher rates of mortality from external causes (HR 1.97; 95% CI, 1.69-2.29), such as accidents and suicides — but there was no significant difference in mortality by non-external causes. The excess mortality rate ratio (EMRR) was 1.52 (95% CI, 1.31-1.76) after adjustments, with the highest risk found in individuals without somatic comorbidity (EMRR 1.99; 95% CI, 1.63-2.43) and between the ages of 18 and 29 (EMRR 2.20; 95% CI, 1.62-2.99). 

Data for this study was collected from Swedish national registers. Treatment-resistant depression was classified as two additional trials of treatment in one episode of depression. Data on sex, history of depression, disorders with use of substances, somatic and psychiatric comorbidities, age, and self-harm was also gathered. Researchers used hazard ratios with 95% confidence intervals to calculate relative risks between patients with treatment-resistant depression and others for mortality due to external and non-external causes.

Related Articles

The study found that patients with treatment-resistant depression may have an increased mortality when compared with those who have non-treatment-resistant depression in specialized psychiatric care, mainly attributed to deaths from external causes. Further research can identify underlying risk factors, treatment, and preventive measures. They found the highest relative mortality among subjects who were young and healthy.


Reutfors J, Andersson TM, Brenner P, et al. Mortality in treatment-resistant unipolar depression: A register-based cohort study in Sweden. J Affect Disord. 2018;238:674-679.