Mixed depression: Toward a conceptual framework

Mixed depression remains nosologically fractured and clinically underrecognized, particularly in the context of major depressive disorder (MDD). As a result, a substantial subgroup of patients is overlooked despite high clinical stakes and possibly a severe illness phenotype. Emerging perspectives increasingly recognize a nuanced and complex psychopathology of mixed depression, though significant gaps persist in empirical guidance for treatment. The DSM-5 mixed specifier represents progress but is undermined by paradoxical exclusion of the crucial symptoms commonly observed in mixed depression. ICD-11 is more inclusive of mixed episodes but lacks recognition of subthreshold mixed features or specifiers. This paper discusses the conceptual underpinnings of mixed depression by critically examining how it is currently defined (nosology), how it presents clinically (phenomenology), and what evidence (empirical data) supports or challenges the current framework. To move forward, it is essential ADDIN ZOTERO_TEMP {Citation}to build evidence towards a conceptually coherent, clinically useful foundation to guide clinical care and treatment approach for MDD with mixed symptoms