Investigation of early and lifetime clinical features and comorbidities for the risk of developing treatment-resistance depression in a 13-year nationwide cohort study

Abstract

Background To investigate the risk of developing treatment-resistant depression among depressive patients by examining clinical features, early prescription patterns, and early and lifetime comorbidities. Methods A total of 31,422 depressive inpatients were followed from diagnostic onset to more than ten-years. treatment-resistant depression was defined by altered antidepressant treatment regimens more than twice or being admitted after received at least two antidepressant treatments. Multiple regression and Cox regression models were used to examine the effects of physical and psychiatric comorbidities, psychosis, and early prescription patterns on the risk of developing treatment-resistant depression. Results Female depressive patients (21.24%) were more likely to become treatment-resistant depression than males (14.02%). Early anxiety disorder was commonly observed in the treatment-resistant depression comparing with non-treatment-resistant depression groups (81.48 vs. 58.96%, p < 0.0001). Lifetime anxiety disorder exhibited the highest population attributable fraction (43.1%). 70% of patients with multiple psychiatric comorbidities developed treatment-resistant depression during follow-up. Results in Cox regression further identified that functional gastrointestinal disorders significantly increased the risk of treatment-resistant depression (aHR = 1.18). A higher dose of antidepressants in early disease course exhibited increased risk for treatment-resistant depression (p < 0.0001). Conclusion Our findings indicate the need to monitor early comorbidities and polypharmacy patterns in patients with major depressive disorder that are associated with an elevated risk for treatment-resistant depression.