Prolactin hyperresponsiveness to D-fenfluramine in drug-free schizophrenic patients: a placebo-controlled study.
BACKGROUND
Functional alterations in the central serotonergic system have been reported in schizophrenia but no conclusive data have been provided. In the present study, we investigated the prolactin (PRL) response to the selective serotonin (5-HT) releasing agent D-fenfluramine in both patients with schizophrenia and matched healthy subjects.


METHODS
Sixteen drug-free schizophrenics and 16 healthy subjects were randomized in a double-blind neuroendocrine test to D-fenfluramine (30 mg p.o.) or placebo. Blood PRL and cortisol concentrations were determined by radioimmunoassay, while plasma levels of D-fenfluramine were measured by mass spectrometry.


RESULTS
In schizophrenic patients, baseline plasma PRL levels were not different from controls, whereas plasma cortisol concentrations were significantly increased (p < .03). The PRL response to D-fenfluramine was significantly enhanced in patients as compared to matched control subjects (p < .005). Schizophrenics meeting Kane's criteria for previous nonresponse to typical neuroleptics exhibited a PRL response to D-fenfluramine significantly higher than non-drug-resistant patients (p < .04). No significant difference in plasma D-fenfluramine concentrations was observed between schizophrenic and healthy subjects.


CONCLUSIONS
These findings suggest a serotonergic hypersensitivity in chronic schizophrenia. This alteration seems to be peculiar to those patients refractory to typical neuroleptics.
Monteleone
P
P
Institute of Psychiatry, University of Naples SUN, Italy.
Tortorella
A
A
Borriello
R
R
Cassandro
P
P
Maj
M
M
D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D011388:Prolactin / Q000097:blood* / Q000378:metabolism*; D012559:Schizophrenia / Q000097:blood*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D005277:Fenfluramine; D006854:Hydrocortisone; D011388:Prolactin; D017367:Selective Serotonin Reuptake Inhibitors