Low-dose dexamethasone challenge in women with atypical major depression: pilot study

Objective: To examine if atypical depression may be associated with hypersuppression of the hypothalamic-pituitary-ad renal (HPA) axis. Method: Eight women with atypical major depression and 11 controls with no history of psychiatric illness, matched on age and body mass index, were challenged with low-dose dexamethasone (0.25 mg and 0.50 mg in random order and 1 week apart). Dexamethasone was self administered at 11 pm, and plasma cortisol samples were drawn at 8 am and 3 pm on the following day. Results: After the 0.50-mg dexamethasone challenge, mean suppression of morning cortisol was significantly greater in patients with atypical depression (91.9%, standard deviation [SD] 6.8%) than in the controls (78.3%, SD 10.7%; p < 0.01). Conclusion: These preliminary data add to the growing body of literature that suggests atypical depression, in contrast to classic melancholia, may be associated with exaggerated negative feedback regulation of the HPA axis.