THE CORTISOL RESPONSE TO CLONIDINE IN ACUTE AND REMITTED DEPRESSED MEN

To assess the relationship between the hypothalamo-pituitary-adrenal ( HPA) axis and the noradrenergic system in patients with major depressi on, 26 normal controls, 32 acutely depressed patients, and 21 patients with remitted depression, all men, were administered intravenous clon idine (2 mug/kg) or placebo. Acute, but not remitted, depressed patien ts had a greater plasma cortisol baseline than did normal controls (t = 2.0, p < 0.03). Only acutely depressed patients had a greater decrea se in plasma cortisol in response to clonidine than to placebo (t = 2. 5, p < 0.02). Statistically controlling for both diurnal variation and baseline cortisol, acute, but not remitted, depressed patients had a greater decrease in plasma cortisol in response to clonidine than did the controls (analysis of covariance: F[1,35] = 4.26, p < 0.05). These results support a state-dependent noradrenergic-HPA axis regulatory d isturbance in depressed patients, suggesting that clonidine inhibits t he elevated plasma cortisol in acute depression but not the normal con centrations observed in remitted depression or healthy controls.