D-fenfluramine-evoked serotonergic responses in olanzapine-treated schizophrenic patients

Antagonist activity at the 5-HT2 receptor may contribute to the therapeutic efficacy of atypical antipsychotics in schizophrenia. This neuroendocrine study examined the in vivo functional serotonergic (5-HT) activity of the atypical antipsychotic olanzapine. We examined central 5-HT, responses by measuring the serum prolactin (PRL) over 5 h in response to 30 mg Of D-fenfluramine (DFEN) in two groups of male schizophrenic patients. Blunted PRL responses to DFEN indicate functional 5-HT, receptor antagonism. Seven patients treated with olanzapine at a mean (S.D.) dose of 13.1 (4.6) for a mean of 28 weeks were compared with a matched group of eight patients who had received no antipsychotic treatment for at least 2 weeks. Baseline PRL levels did not differ significantly in the two patient groups and were within the normal range. The olanzapine-treated patients showed a significantly lower maximal DFEN-evoked PRL response and a significantly lower group X time overall PRL release compared with the untreated patient group. We have previously demonstrated a similar degree of functional in vivo 5-HT2 antagonism with the atypical antipsychotic clozapine. This study thus suggests that this activity may not contribute to the unique clinical efficacy of clozapine. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.