Brenner P, et al. - Researchers examined how substance use disorders (SUD) is associated with treatment-resistant depression (TRD). They conducted nested case-control study. They established a prospectively followed cohort of antidepressant initiators with depression (n = 121,669) from 2006 to 2014 utilizing data on prescribed drugs and diagnoses from specialized healthcare. Of these, TRD cases comprised 15,631 patients (13%), with at least three treatment trials within a single depressive episode. They matched each case with TRD with five controls with depression on sociodemographic data. Outcomes revealed a positive association of recent or current substance use disorders with treatment resistance among patients initiating treatment for depression. They observed almost double risk for TRD in correlation to having any SUD during, or ≤ 180 days before the start of, antidepressant treatment.