Abnormal neuroendocrine responsivity to clomipramine in depression.

We used a pharmacologic probe that measures the neuroendocrine response to acute, intravenous "challenge" with the serotonin re-uptake inhibitor, clomipramine, in our studies of the biochemical bases of depressive illness. In two studies conducted at different sites, depressed patients consistently demonstrated blunted prolactin responses to clomipramine, compared with healthy control subjects. In order to clarify the mechanisms that might account for this abnormal neuroendocrine response to clomipramine in depression, we administered a thyrotropin-releasing hormone (TRH) stimulation test to 7 depressed patients who had also received a clomipramine challenge test. Although these patients demonstrated blunted prolactin responses to clomipramine, their prolactin responses to TRH were robust. These observations suggest that the blunted prolactin response to clomipramine in depression is not attributable to diminished hormonal secretory capacity in anterior pituitary lactotrophs and may be a reflection of dysregulation in central serotonergic systems.