Effect of clozapine on d-fenfluramine-evoked neuroendocrine responses in schizophrenia and its relationship to clinical improvement.

Abstract

Clozapine is an effective antipsychotic that has high affinity for serotonin type 2 (5-HT2) receptors. The importance of 5-HT antagonism in the overall clinical efficacy of clozapine is unclear. Using a neuroendocrine strategy we tested the hypothesis that clinical response to clozapine is related to alteration in 5-HT function. Ten treatment-resistant schizophrenic subjects were treated with clozapine for a mean of 10.3 (s.e. 0.9) weeks; d-fenfluramine (DFEN) challenge tests were performed before and after treatment with concurrent clinical ratings (BPRS, SAPS, SANS) made at the time of testing. All patients showed clinical improvement following treatment with clozapine. In addition, clozapine produced a significant attenuation of prolactin (PRL) and cortisol (CRT) response to DFEN challenge. Change in symptom ratings correlated significantly with reduction in PRL response to DFEN challenge. These data show that functional alterations occur in the 5-HT system following response to clozapine and lend support to studies suggesting that 5-HT is an important component to the spectrum of action of clozapine.