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  • Title: Effect of clozapine on d-fenfluramine-evoked neuroendocrine responses in schizophrenia and its relationship to clinical improvement.
    Author: Curtis VA, Wright P, Reveley A, Kerwin R, Lucey JV.
    Journal: Br J Psychiatry; 1995 May; 166(5):642-6. PubMed ID: 7620750.
    Abstract:
    BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.
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