The effect of treatment with ketoconazole on central CRH systems of depressed patients

Objectives: Steroid-synthesis inhibitors are reported to reduce psychopathology in treatment-resistant depressed patients. Methods We studied the effect of a 3-week treatment with ketoconazole on the evening plasma concentrations of cortisol, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S) and adrenocorticotrope hormone (ACTH) as well as morning cerebrospinal fluid (CSF) concentrations of cortisol, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) in six elderly treatment-resistant depressed patients. Results: While we found plasma cortisol concentrations to be unchanged, a decline in plasma DHEA-S concentrations indicated effective steroid-synthesis inhibition. In morning CSF we found CRH concentrations that did not change. Conclusions: Our preliminary observations indicate that the treatment of depressed patients with the steroid-synthesis inhibitor ketoconazole does not lead to a major increase in CSF CRH secretion.