Relationship between prolactin response and antipsychotic effect of thioridazine in psychiatric patients

Summary

Neuroleptic drugs may exert their antipsychotic effect by interference with central dopaminergic mechanisms. Tuberoinfundibular dopaminergic neurons may also be affected, which will increase prolactin secretion from the pituitary. Accordingly, a study has been made in 23 patients with acute paranoid psychosis, treated with thioridazine, of repeated ratings of psychiatric symptoms (CPRS) and of serum prolactin concentration. There was a close correlation between the serum concentration of prolactin and low doses of thioridazine, but at higher doses the increase in prolactin level gradually levelled off. At a given dose the prolactin response to thioridazine showed large interindividual variation and female patients had higher serum prolactin concentrations than males. The prolactin response to thioridazine was unaffected by time of treatment, age or body weight. In individual patients a correlation was found between serum prolactin level and amelioration of psychiatric symptoms, as reflected by the psychiatric rating score (p<0.001). After normalization of the data, the same relationship was also found for the entire group of patients. The dose-response relationship of prolactin to thioridazine showed saturation kinetics and linear transformation by a Woolfe-plot was done. Therefore, it appears possible to predict the thioridazine dose that would give the maximal prolactin response (and maximal clinical effect) and thereby optimize the regimen of antipsychotic medication in the individual patient.