Neuroendocrine response to antipsychotics:: Effects of drug type and gender

Background: To study the influences of drug type and gender on the neuroendocrine response to neuroleptic treatment we compared the endocrine actions of two neuroleptics with different receptor affinity profiles-a substituted benzamide, amisulpride, a selective D-2-like dopamine antagonist; and a thioxanthene, flupenthixol, a mixed D-1/D-2-like antagonist also blocking serotonin, H-1, and D-1 receptors-on anterior pituitary hormone secretion in schizophrenic patients (DSM-III-R). Methods: Blood was withdrawn at 15-min intervals to assess basal secretion of prolactin, growth hormone (GH), and thyroid-stimulating hormone (TSH). Four hundred micrograms of thyrotropin-releasing hormone (TRH) was injected IV to investigate drug effects on TRH-stimulated secretion of prolactin TSH, and GH. Results: Prolactin plasma levels were markedly elevated in both treatment groups. In female, but not in male patients, this elevation was significantly more pronounced under amisulpride than under flupenthixol, The prolactin response to TRH was significantly blunted by amisulpride only in male subjects. While basal TSH secretion was significantly increased by both compounds, TRH-stimulated TSH secretion was elevated only in patients treated with amisulpride. Low basal prolactin levels predicted improvement of negative symptoms in patients treated with amisulpride. Conclusions: Amisulpride's more pronounced endocrine effects may be a reflection of its distinguished pharmacology and pharmacokinetics. Biol Psychiatry 1999;45: 89-97 (C) 1999 Society of Biological Psychiatry.