Cumulative depressive burden, functional impairment, depressive symptomatology and treatment response in Major Depressive Disorder: results from the STAR∗D and GSRD studies

Background: Major Depressive Disorder (MDD) is a frequently recurrent condition that substantially impairs functioning; however, the contribution of illness course to functional impairment remains less well understood. This study investigated the association between Cumulative Depressive Burden-CDB (a composite measure incorporating lifetime disease duration, number of depressive episodes and duration of current episode) and functioning, depressive symptomatology and treatment response in MDD. Associations with the individual components of CDB were also examined. Materials and methods: Data were collected in the context of the “Group for the Study of Resistant Depression” (GSRD) and “Sequenced Treatment Alternatives to Relieve Depression” (STAR∗D) trials. Functioning was assessed using the Work and Social Adjustment Scale in STAR∗D and the Sheehan Disability Scale in GSRD. Depressive symptoms were assessed real-time in the STAR∗D (through the 30-item Inventory for Depressive Symptomatology) and retrospectively in the GSRD (through the retrospective Montgomery-Äsberg depression rating scale). Linear or logistic regression models were used to investigate the associations between CDB, depressive symptoms, functioning and treatment response. Results: The individual CDB components showed different patterns of association across the two cohorts, while higher CDB was consistently associated with worse functioning. Associations with depressive symptom dimensions were less consistent between datasets. Higher CDB was strongly associated with poorer treatment response in the GSRD sample. Conclusions: CDB may represent a clinically meaningful operational construct reflecting longitudinal illness load in MDD. Its association with functional impairment and treatment response supports a more comprehensive conceptualization of illness course in MDD.