Neuroendocrine (HPA axis) and clinical correlates during fluvoxamine and amitriptyline treatment

The effect of amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) axis activity was compared with that of fluvoxamine in 38 patients suffering from DMS-IV major depressive disorder. Basal plasma adrenocorticotropic hormone and cortisol levels were determined in the so-called "observation window" of an hour (08:00-09:00 h), and cortisol levels were determined again at 20:00 h. Clinical and biochemical assessments were performed before therapy (T₀), at day 14 (T₁₄), and at day 42 (T ₄₂) of the course of antidepressant treatment. At T₀, neuroendocrine parameters did not differ in patients from those in controls, except for the ratio between cortisol levels at 20:00 h and the mean level of the "window" (ratio F₂₀/F₈), which was significantly higher, suggesting a dysregulation of the circadian pattern of cortisol. Although a decrease in the ratio F₂₀/F₈ was already apparent at T₁₄ of both treatments, the repeated measures analysis of variance failed to demonstrate a significant variation with time (T₀, T₁₄, and T₄₂) and with treatment (amitriptyline and fluvoxamine) for any hormonal measure. At T₄₂, both treated groups showed a similar level of clinical improvement. Our results did not demonstrate any effect of antidepressant therapy on the cortisol circadian rhythm abnormality.