Heterogeneity in major depression and its melancholic and atypical specifiers: a secondary analysis of STAR*D

The melancholic and atypical specifiers for a major depressive episode (MDE) are supposed to reduce heterogeneity in symptom presentation by requiring additional, specific features. Fried et al. (2020) recently showed that the melancholic specifier may increase the potential heterogeneity in presenting symptoms. In a large sample of outpatients with depression, our objective was to explore whether the melancholic and atypical specifiers reduced observed heterogeneity in symptoms.

We used baseline data from the Inventory of Depression Symptoms (IDS), which was available for 3,717 patients, from the Sequenced Alternatives to Relieve Depression (STAR*D) trial. A subsample met criteria for MDE on the IDS ("IDS-MDE"; N =2,496). For patients with IDS-MDE, we differentiated between those with melancholic, non-melancholic, non-melancholic, atypical, and non-atypical depression. We quantified the observed heterogeneity between groups by counting the number of unique symptom combinations pertaining to their given diagnostic group (e.g., counting the melancholic symptoms for melancholic and non-melancholic groups), as well as the profiles of DSM-MDE symptoms (i.e., ignoring the specifier symptoms).

When considering the specifier and depressive symptoms, there was more observed heterogeneity within the melancholic and atypical subgroups than in the IDS-MDE sample (i.e., ignoring the specifier subgroups). The differences in number of profiles between the melancholic and non-melancholic groups were not statistically significant, irrespective of whether focusing on the specifier symptoms or only the DSM-MDE symptoms. The differences between the atypical and non-atypical subgroups were smaller than what would be expected by chance. We found no evidence that the specifier groups reduce heterogeneity, as can be quantified by unique symptom profiles. Most symptom profiles, even in the specifier subgroups, had five or fewer individuals.

We found no evidence that the atypical and melancholic specifiers create more symptomatically homogeneous groups. Indeed, the melancholic and atypical specifiers introduce heterogeneity by adding symptoms to the DSM diagnosis of MDE.