Prolactin responses to acute clomipramine and haloperidol of male schizophrenic patients in a drug-free state and after treatment with clozapine or with olanzapine

Abstract

Atypical neuroleptics share a common feature, showing higher affinity for 5-HT2 receptors than for D2 dopamine receptors, but show considerable differences in their clinical and pharmacological properties. In clinical doses, they occupy serotonergic receptors near saturation, but show considerable differences regarding the D2 receptor occupancies, with clozapine showing the lowest degree of occupation. We assessed serotonergic and dopaminergic receptor responsiveness in two groups of male schizophrenic patients, one treated with the atypical neuroleptic clozapine (14 patients, doses 200-600 mg/d) and the other treated with olanzapine (11 patients, doses 10-30 mg/d). We measured the prolactin responses to the acute administration of a serotonergic drug, clomipramine, and a dopaminergic one, haloperidol. Tests were first performed in the drug-free state, and were repeated after the patients had been treated with stable doses of either drug for six weeks. Clomipramine administration induced significant increases of prolactin in the drug-free state. These responses were eliminated after treatment of the patients with either drug, thereby indicating a high 5-HT receptor occupancy by both clozapine and olanzapine. The prolactin responses to haloperidol were not altered after treatment with clozapine, but were significantly reduced after the olanzapine treatment. The baseline prolactin levels were not influenced by clozapine treatment, and were moderately but significantly increased after treatment with olanzapine. The results indicate that there is a difference between the two drugs in their capacity to block dopamine receptors at the hypothalamus-pituitary level, and match the results obtained by SPECT receptor binding studies for striatal dopamine receptors.