A mixed state core for melancholia: an exploration in history, art and clinical science

Objective: We argue for a mixed state core for melancholia comparing concepts of melancholia across centuries using examples from art, history and scientific literature. Method: Literature reviews focusing on studies from Kraepelin onward, DSM-IV classification and view-points from clinical experience highlighting phenomenologic and biologic features as predictors of bipolar outcome in prospective studies of depression. Results: Despite the implied chemical pathology in the term endogenous/melancholic depression, frequently reported glucocortical and sleep neurophysiologic abnormalities, there is little evidence that melancholia is inherited independently from more broadly defined depressions. Prospective follow-up of 'neurotic' depressions have shown melancholic outcomes in as many as a third; hypomania has also been observed in such follow-up. Conclusion: These findings and considerations overall do suggest that melancholia as defined today is more closely aligned with the depressive and/or mixed phase of bipolar disorder. Given the high suicidality from many of these patients the practice of treating them with antidepressant monotherapy needs re-evaluation.