Antipsychotics: impact on prolactin levels

Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, galactorrhoea, sexual dysfunction, breast engorgement and osteoporosis. Since the mid-1970s, the impact of antipsychotics on human prolactin (hPrl) levels has been investigated. Baseline levels of hPrl were found to be similar in healthy controls and patients who were diagnosed as having schizophrenia. Short-term acute studies done after single parenteral or oral doses of phenothiazines found rapid two- to tenfold increases in hPrl. Similar increases were found in longer term studies that reported increases of three times in both men and women after 3 days that doubled again after several weeks of treatment. A study of longer term injectable fluphenazine enanthate found that elevation induced by a single injection lasted up to 28 days. The same results with significant increases have been reported with the butyrophenone, haloperidol. Substantial increases are found after single injections (up to nine times) and after weeks of treatment (up to three times sustained). Thus, early literature believed that there might be an association between these induced changes and response to therapy. However, prolactin is secreted by the anterior pituitary and is under inhibitory control of dopamine released from the tuberoinfundibular neurones. Thus, increases in prolactin are due to antipsychotic impact on tuberoinfundibular tract, one of four dopamine-related tracts. With the application of clozapine and other atypical antipsychotics, it was found that medications can successfully treat psychosis without increasing hPrl. In fact, early single-dose trails found clozapine to reduce hPrl by 16%. Later studies replicated this result and also found that up to 6 weeks of administration led to reductions in hPrl of up to 80%. Risperidone, however, has been found to persistently elevate hPrl in studies, despite its impact on other receptor sites. Olanzapine, quetiapine and ziprasidone have all been found to have little effect or produce decreases in hPrl. Most recently, aripiprazole, in early studies, appears to produce significant reductions in hPrl while maintaining therapeutic efficacy for psychosis.