The rationale for subtyping depression into atypical and melancholic in research and clinical settings: A narrative review.

Background: Given the well-known heterogeneity of depression, subtyping into atypical and melancholic depression according to clinical manifestations has gained increasing interest in research, to define more homogenous groups. This narrative review focuses on studies investigating indicators of the validity of the subtyping of depression into atypical vs. melancholic, including familial aggregation patterns and course of illness as well as differences between these subtypes regarding sociodemographic, psychological and biological characteristics.

Results: There is some limited evidence for the specific familial aggregation and longitudinal stability of the atypical depression subtype, but weaker evidence for the validity of the melancholic subtype. In contrast, there is good evidence, based on multiple mostly cross-sectional studies with partially large samples, to support differences between the atypical and the melancholic subtypes in sex distribution, metabolic and inflammatory marker levels and HPA-axis functioning. There is also some evidence for a differential lifetime prevalence between subtypes for comorbid anxiety and substance use disorders as well as for dietary habits.

Limitations: Heterogeneity of subtype definitions and data on familial aggregation and the longitudinal stability of these subtypes is scarce.

Conclusions: Although the reviewed literature provides support for subtyping into atypical and melancholic depression, the current DSM definitions of these subtypes are not optimal. In the future, an enhanced understanding of the biological pathways underlying depression should help to define subtypes or dimensions that are more closely related to their underlying biological mechanisms, thereby promoting the identification of patient subgroups that are more likely to respond to specific types of treatment.