Neuroendocrine responsivities of the pituitary dopamine system in male schizophrenic patients during treatment with clozapine, olanzapine, risperidone, sulpiride, or haloperidol
Background Atypical antipsychotic drugs, in clinical doses, occupy 5-HT2 receptors near saturation, while D2 dopamine receptors, assessed usually in striatum by SPECT or PET methods, are occupied to different degrees. We hypothesized that these differences in D2 receptor occupancies may also be evaluated by a neuroendocrine approach, namely by measuring the plasma prolactin responses to i. m. administered haloperidol, since the expected elevations depend mainly on the free remaining D2 receptors in the tuberoinfundibular tract. Methods We measured the plasma prolactin levels at 0, 30, 60, 90, and 120 minutes after administration of 5 mg haloperidol i. m. in six groups of male patients with schizophrenia: a) 33 patients in a drug-free state, b) 15 patients on treatment with clozapine (range 200–600 mg/day), c) 15 patients on olanzapine (10–30 mg/day), d) 14 patients on risperidone (8–16 mg/day), e) 23 patients on haloperidol (10–40 mg/day), f) 14 patients on sulpiride (600–1600 mg/day). Data were also obtained from a group of 14 healthy male control subjects. The differences in baseline prolactin levels and in the responses to acute haloperidol of the seven groups were compared. Results The baseline prolactin levels did not differ significantly in the groups of controls (8.3±3.8 ng/ml), drug-free patients (8.0±3.6) and patients treated with clozapine (7.7±3.8), they were moderately elevated in patients treated with olanzapine (16.8±8.9), elevated in patients on haloperidol (34.4±17.3), and they were even higher in the groups of patients treated with risperidone (54.9±22.4) or sulpiride (58.8±27.0). All groups of patients gave attenuated prolactin responses to i. m. haloperidol compared to healthy controls. During treatment with haloperidol, risperidone, or sulpiride, no significant prolactin increases after i. m. haloperidol were observed. The group treated with olanzapine gave significant prolactin increases, which were lower than those obtained in the group of patients treated with clozapine, who gave responses similar to that of the drug-free patients. Conclusions Plasma prolactin levels and responses to i. m. haloperidol of patients on treatment with antipsychotic drugs, reflect the prolactin release potencies of the drugs, which are related, but not restricted, to their affinities to D2 dopamine receptors. According to the prolactin baseline levels and responses to i. m. haloperidol, the drugs of this study can be categorized for their potency to the pituitary dopamine system that controls prolactin release, as follows: sulpiride > risperidone > haloperidol > olanzapine > clozapine. This categorization is similar to that obtained by binding studies in striatal D2 dopamine receptors using brain imaging techniques.