EFFECT OF CLOZAPINE ON D-FENFLURAMINE-EVOKED NEUROENDOCRINE RESPONSESIN SCHIZOPHRENIA AND ITS RELATIONSHIP TO CLINICAL IMPROVEMENT

Background. Clozapine is an effective antipsychotic that has high affi nity for serotonin type 2 (5-HT2) receptors. The importance of 5-HT an tagonism in the overall clinical efficacy of clozapine is unclear. Usi ng a neuroendocrine strategy we tested the hypothesis that clinical re sponse to clozapine is related to alteration in 5-HT function. Method. Ten treatment-resistant schizophrenic subjects were treated with cloz apine for a mean of 10.3 (s.e. 0.9) weeks; d-fenfluramine (DFEN) chall enge tests were performed before and after treatment with concurrent c linical ratings (BPRS, SAPS, SANS) made at the time of testing. Result s. All patients showed clinical improvement following treatment with c lozapine. 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 res ponse to DFEN challenge. Conclusions, These data show that functional alterations occur in the 5-HT system following response to clozapine a nd lend support to studies suggesting that 5-HT is an important compon ent to the spectrum of action of clozapine.