The Effect of Antipsychotics on Prolactinoma Growth: A Radiological and Serological Analysis

Many antipsychotic (AP) medications work by reducing dopamine levels. As hyperdopaminergia is known to cause psychosis, antipsychotics work to relieve these symptoms by antagonizing dopamine receptors and lowering dopamine levels. Dopamine is also a known negative modulator of the prolactin pathway, which allows for drug agents like dopamine agonists (DAs) to be incredibly effective in managing tumors that secrete excess prolactin (prolactinomas). While the effects of DAs on prolactinoma size and growth have been studied for decades, the effects of APs on prolactinoma size remain to be seen. We hope to investigate the effects of APs on prolactinomas by conducting a thorough PubMed search, including patients with diagnosed prolactinoma on concurrent AP therapy. Our search led to 27 studies with a total of 32 patients. We identified themes regarding seven antipsychotics: risperidone, haloperidol, amisulpride, thioridazine, aripiprazole, olanzapine, and clozapine. Risperidone, haloperidol, amisulpride, and thioridazine caused a significant increase in prolactin in most cases where they were used, and prolactin decreased after their discontinuation. For example, risperidone discontinuation resulted in a decrease in prolactin levels by an average of 66%, while haloperidol, amisulpride, and thioridazine discontinuation lowered prolactin by an average of 82%, 72%, and 89.7%, respectively. However, there were some exceptions in regard to risperidone, haloperidol, and thioridazine, where prolactin levels were not as severely affected. Aripiprazole, olanzapine, and clozapine all had significant reductions in prolactin levels when patients were switched from another antipsychotic, such as risperidone or haloperidol. The average percent decrease in prolactin when switched to aripiprazole was 67.65%, while it was 54.16% and 68% for olanzapine and clozapine, respectively. The effect of individual antipsychotics on prolactinoma size was difficult to ascertain, as imaging was not obtained (or indicated) after every antipsychotic switch, and many patients were taking dopamine agonists concurrently. Therefore, it would be difficult to ascertain which factor affected size more. Also, some patients received surgery or radiotherapy, which completely negated our ability to make any assertions about the effects of certain pharmacological agents. Although it is difficult to ascertain the role that antipsychotic medications play in the formation of prolactinoma, we have found that the cessation of certain antipsychotic medications may lead to a reduction in prolactin levels and possibly the presence of a measurable prolactinoma.