The impact of depression on functioning: Relation to medication response and other predictors

Depression is a leading cause of disability worldwide, profoundly impairing occupational, social, and family functioning. We aimed to identify socio-demographic and clinical variables associated with functional impairment across these domains in patients suffering from major depressive disorder (MDD), with a particular focus on treatment-resistant depression (TRD). 755 patients with MDD and treated with antidepressants for at least four weeks were included from the multicentric study of "Group for the Study of Resistant Depression". Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (retrospective and current), while functional impairment was measured with the Sheehan Disability Scale (SDS). Univariate and multivariate models adjusted for age, sex, and depression severity were used. Across all domains, higher depression severity, particularly marked by suicide risk, anhedonia, and inpatient status, was strongly linked to higher disability. In non-TRD patients, somatic comorbidities, including diabetes, were significant predictors of social and family functioning impairment, whereas in TRD patients, family-related factors such as a higher number of children and living alone were associated with impaired functioning. These findings underscore the heterogeneous determinants of disability in depression and suggest that tailored treatment approaches addressing both clinical severity and specific socio-demographic factors may improve functional outcomes.