title: Neuroendocrine evidence that clozapine's serotonergic antagonism is relevant to its efficacy in treating hallucinations and other positive schizophrenic symptoms.
abstract: 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.
authors.affiliation: Division of Psychiatry, Homerton Hospital, London.
authors.forename: H
authors.initials: H
authors.lastname: Jones
authors.forename: V A
authors.initials: VA
authors.lastname: Curtis
authors.forename: P
authors.initials: P
authors.lastname: Wright
authors.forename: J V
authors.initials: JV
authors.lastname: Lucey
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005277:Fenfluramine; D011388:Prolactin; D003024:Clozapine