Neuroendocrine Evidence That Clozapine's Serotonergic Antagonism Is Relevant to Its Efficacy in Treating Hallucinations and Other Positive Schizophrenic Symptoms

• Published in: The American journal of psychiatry Vol. 155; no. 6; pp. 838 - 840
• Main Authors: Jones, Hugh, Curtis, Vivienne A., Wright, Padraig, Lucey, James V.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01-06-1998; American Psychiatric Association
• Subjects: Adult; Antipsychotic Agents - pharmacology; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Clozapine - pharmacology; Clozapine - therapeutic use; Drug therapy; Female; Fenfluramine - pharmacology; Hallucinations - drug therapy; Hallucinations - psychology; Humans; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Prolactin - blood; Psychiatric Status Rating Scales; Psychiatry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Serotonin - drug effects; Schizophrenia; Schizophrenia - blood; Schizophrenia - drug therapy; Schizophrenic Psychology; Serotonin Antagonists - pharmacology; Serotonin Antagonists - therapeutic use; Treatment Outcome; Human; Serotonin; Neuroleptic; Psychotropic; Schizophrenia; Clozapine; Serotonine receptor; Psychosis; Protein hormone; Chemotherapy; Treatment; Adenohypophyseal hormone; Prolactin; Neurotransmitter; Atypical; Antagonist; Mechanism of action; Release
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/ajp.155.6.838

OBJECTIVE: The authors examined the effect of prolonged clozapine treatment on central serotonergic (5-HT) function in schizophrenia. METHOD: 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.