
The DSM-5 mixed features specifier excludes irritability, psychomotor agitation, and distractibility from the diagnostic criteria for mixed depression, deeming them non-specific symptoms that overlap with pure major depressive episodes. This exclusionary decision has created significant diagnostic and therapeutic challenges. Empirical evidence demonstrates that DSM-5 criteria identify only 0–12% of depressed patients with mixed features, compared with 33–47% when broader criteria inclusive of agitation and irritability are applied. These excluded symptoms are not incidental; they are the most prevalent features of clinically observed mixed depression. The exclusion of these core symptoms sits in tension with both clinical observation and Kraepelinian tradition, yielding what has been aptly described as "a clinical construct nowhere to be found." This critical review argues that irritability and psychomotor agitation should be reconsidered as central diagnostic features of mixed depression. The current specifier's failure to capture diagnostically relevant mixed states has significant implications for patient safety and treatment outcomes and warrants nosological revision. This manuscript is a narrative critical review and does not present original clinical data.
