NEUROENDOCRINE EVIDENCE THAT CLOZAPINES SEROTONERGIC ANTAGONISM IS RELEVANT TO ITS EFFICACY IN TREATING HALLUCINATIONS AND OTHER POSITIVE SCHIZOPHRENIC SYMPTOMS

Objective: The authors examined the effect of prolonged clozapine trea tment on central serotonergic (5-HT) function in schizophrenia. Method : Prolactin responses to the S-PIT 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 tre atment. The second group was tested after a mean of 20 months of cloza pine treatment. Results: The prolactin response was significantly blun ted in these 20 patients treated with clozapine. There was a significa nt positive correlation between d-fenfluramine-evoked prolactin releas e and the overall positive symptom score and the hallucination and del usion subscores of the Scale for the Assessment of Positive Symptoms. Conclusions: Blunted S-HT-mediated prolactin responses in schizophreni c patients receiving clozapine monotherapy for up to 20 months were co rrelated with reductions in positive symptoms. This suggests that S-HT antagonism is relevant to clozapine's efficacy in alleviating halluci nations and other positive schizophrenic symptoms.