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

Antagonist activity at the 5-HT(2) 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(2) 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(2) 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-HT(2) antagonism with the atypical antipsychotic clozapine. This study thus suggests that this activity may not contribute to the unique clinical efficacy of clozapine.