Neuroendocrine evidence that clozapine's serotonergic antagonism is relevant to its efficacy in treating hallucinations and other positive schizophrenic symptoms.
OBJECTIVE
The authors examined the effect of prolonged clozapine treatment on central serotonergic (5-HT) function in schizophrenia.


METHODS
Prolactin responses to the 5-HT releasing agent d-fenfluramine were measured in two groups of 10 schizophrenic subjects. The first group was tested twice, before and after a mean of 10 weeks of clozapine treatment. The second group was tested after a mean of 20 months of clozapine treatment.


RESULTS
The prolactin response was significantly blunted in these 20 patients treated with clozapine. There was a significant positive correlation between d-fenfluramine-evoked prolactin release and the overall positive symptom score and the hallucination and delusion subscores of the Scale for the Assessment of Positive Symptoms.


CONCLUSIONS
Blunted 5-HT-mediated prolactin responses in schizophrenic patients receiving clozapine monotherapy for up to 20 months were correlated with reductions in positive symptoms. This suggests that 5-HT antagonism is relevant to clozapine's efficacy in alleviating hallucinations and other positive schizophrenic symptoms.
Jones
H
H
Division of Psychiatry, Homerton Hospital, London.
Curtis
V A
VA
Wright
P
P
Lucey
J V
JV
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D006212:Hallucinations / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008297:Male; D011388:Prolactin / Q000097:blood*; D011569:Psychiatric Status Rating Scales; D011985:Receptors, Serotonin / Q000187:drug effects; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005277:Fenfluramine; D011388:Prolactin; D003024:Clozapine