Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study

IMPORTANCE The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of many observational studies on TRD is limited. OBJECTIVE To estimate the burden of TRD in a large population-wide cohort in an area with universal health care by including data from both health care types (psychiatric and nonpsychiatric) and, further, to develop a prognostic model for clinical use. DESIGN, SETTING, AND PARTICIPANTS This cohort study, a population-based observational study, assessed data from the Stockholm MDD Cohort for episodes of major depressive disorder (MDD) between 2010 and 2017 that fulfilled predefined criteria for TRD (>_3 consecutive antidepressant treatments). Data analysis was performed from August 2020 to May 2022. MAIN OUTCOMES AND MEASURES Outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality, and intentional self-harm and, in the prognostic model, TRD. RESULTS A total of 158169 unipolar MDD episodes (in 145 577 patients) were identified between January 1, 2012, and December 31, 2017 (64.7% women; median [IQR] age, 42 years [30-56]). Of these, 12 793 episodes (11%) fulfilled criteria for TRD. The median (IQR) time from the start of MDD episode to TRD was 552 days (294-932). Selective serotonin reuptake inhibitor was the most common class of antidepressant treatment in all treatment steps, and 5907 patients (46.2%) received psychotherapy at some point before initiation of the third pharmacological antidepressant treatment. Compared with matched non-TRD episodes, TRD episodes had more inpatient bed-days (mean, 3.9 days; 95% CI, 3.6-4.1, vs 1.3 days; 95% CI, 1.2-1.4) and more lost workdays (mean, 132.3 days; 95% CI, 129.5-135.1, vs 58.7 days; 95% CI, 56.8-60.6) 12 months after the index date. Anxiety, stress, sleep disorder, and substance use disorder were all more common comorbid conditions in TRD ...