Risperidone Induced Hyperprolactinemia Levels-Never Seen Before

Introduction : A common side effect of Risperidone is hyperprolactinemia in both genders, occurring in approximately 30-80% of female patients. Risperidone typically raises serum prolactin to about 45-80 ng/mL even with prolonged use. In drug-induced hyperprolactinemia, the prolactin levels rarely exceed 100 ng/mL. Here, we present a case in which the prolactin level was elevated to over 700ng/mL on risperidone without a pituitary adenoma.

Case Description : The patient is a 45-year-old female on SC risperidone for one year due to schizoaffective disorder bipolar type under psychiatric care. She presented with secondary amenorrhea of one year and milk discharge from the breast of six years despite not being pregnant/breastfeeding. She had been on IM paliperidone injections for four years before risperidone. The patient’s physical exam was grossly normal. Labs were significant for prolactin elevation at 730 ng/mL. The rest of her hormonal panel was essentially normal, including FSH, LH, Estradiol, Testosterone, Cortisol, and IGF-1, with a negative pregnancy test. MRI pituitary was reported normal, with no mass/hyperplasia. After requesting the psychiatrist, she was switched from SC risperidone to IM Aripiprazole. Three weeks after switching medications, her prolactin level decreased to 127.7 ng/mL and eventually normalized in 7-8 months to 22.6 ng/mL. After 1-2months, her menstrual cycle returned to normal, and her nipple discharge ceased 3 months after the risperidone was stopped.

Discussion : The mechanism of risperidone-induced hyperprolactinemia is through central signaling processes, but the exact signaling pathway is currently under investigation. Risperidone may mediate the transcriptional regulation of arcuate hypothalamic nucleus (Arc) neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the paraventricular hypothalamic nucleus (PVN). Furthermore, risperidone-induced decreased dopamine synthesis in the PVN leads to hyperprolactinemia by reducing the dopamine-induced inhibition of prolactin release. The usual prolactin level for patients taking risperidone is elevated only to the 60-80ng/mL level, but in some patients, it can go as high as 200ng/dL. As the serum level of risperidone increases, prolactin levels typically increase to a plateau level of 80-100 ng/mL. Levels above 200 ng/mL often indicate a lactotrophic adenoma. Our patient did not have any detectable pituitary adenoma on MRI. After discontinuing the risperidone, her prolactin levels gradually normalized, confirming the etiology of risperidone-induced hyperprolactinemia.