Cortisol and growth hormone responses to the 5-HT1A agonist gepirone in depressed patients.

The 5-HT1A agonist properties of gepirone were used to test for effects on serum cortisol levels in humans, 90 min after a 10 mg oral dose. Fourteen patients with major depression were tested in a single-blind, within-subjects, placebo design. Serum cortisol levels were significantly higher 90 min after gepirone compared to placebo (p less than 0.05). Baseline Hamilton depression ratings were correlated with the serum cortisol levels after acute administration of gepirone (r = 0.54, p less than 0.05), but not placebo. Cortisol levels after a 10 mg gepirone challenge were significantly (p less than 0.02) attenuated after 3-6 weeks chronic administration of gepirone. These preliminary findings suggest that relatively low doses of gepirone may stimulate human cortisol secretion in depressed patients, and cortisol levels after gepirone challenge may correlate with depression severity. Furthermore, a desensitization to gepirone's effects on cortisol may occur after chronic gepirone administration.