Paradoxical Cortisol Responses to Dextroamphetamine in Endogenous Depression

Dextroamphetamine hydrochloride was administered intravenously (IV) in the morning and evening to 22 unmedicated patients with severe endogenous depressions and 18 normal control subjects. While the normal subjects generally had a sharp increase in plasma cortisol level by 30 minutes after drug administration, two thirds of the depressed patients showed instead a paradoxical suppression of cortisol levels by 60 minutes. Discrimination between normal subjects and depressives was greatest in the evening. These results are consistent with other reports of abnormal cortisol responses in depressed patients to smaller IV doses of dextroamphetamine and larger doses of methamphetamine hydrochloride. A defect in activation of noradrenergic α receptors may account, in part, for the abnormal cortisol responses. The dextroamphetamine cortisol test in other patient populations requires study before its diagnostic use in endogenous depression can be established.