The effects of intravenous clomipramine on neurohormones in normal subjects

The neuroendocrine effects of iv administration of clomipramine (CMI), a serotonin reuptake inhibitor, were studied in normal subjects. Under double blind, placebo-controlled conditions, single 10- and 20-mg doses of CMI were administered. Ten milligrams of CMI led to significant increases in plasma PRL and cortisol concentrations; plasma ACTH increased slightly but not significantly. In contrast, plasma GH, melatonin, and norepinephrine concentrations did not increase. Plasma PRL, ACTH, and cortisol levels increased significantly after 20 mg CMI; again, there were no significant changes in plasma GH, melatonin, or norepinephrine concentrations. All subjects tolerated the 10-mg dose well, but the 20-mg dose caused nausea in three of six subjects. Desmethylclomipramine, a metabolite that inhibits reuptake of norepinephrine, was not detectable in plasma after either CMI dose. These results support the hypothesis that serotonin is involved in the regulation of PRL, cortisol, and ACTH in humans.