Follow-Up Study of a Pharmacovigilance Signal

Abstract

Pharmacovigilance studies of spontaneous adverse event report databases are used to raise hypotheses about potential safety events. Such studies have found a disproportionately higher number of pituitary tumor reports for risperidone. Because there is a high prevalence of clinically "silent" pituitary adenomas, any increased workup in risperidone users, for example, secondary to hyperprolactinemia, might account for the increased reports. We undertook a detailed study of medical record-confirmed newly diagnosed pituitary tumors with mass effect in patients prescribed antipsychotics to evaluate the effect of risperidone. We conducted retrospective studies in 2 large administrative health care databases with access to medical records. Patients were classified into risperidone or other atypical antipsychotic exposure groups. Records with administrative codes indicative of possible cases in the follow-up period were reviewed to confirm the diagnosis of new pituitary tumor and presence of mass effects. The hazard ratio of confirmed pituitary tumors with mass effect was 1.0 (95% confidence interval, 0.5-1.9). Whereas the precision of the hazard ratio was limited by low event rates, despite examination of 409,823 patients' records, ancillary analyses supported the interpretation of no elevated risk. Evidence was found for detection bias that may explain previous pharmacovigilance findings. There was no evidence of increased risk of pituitary tumor with mass effect with risperidone in either cohort or case-control analyses. We cannot rule out a small risk (<2-fold), or a risk that may develop with additional years of exposure or follow-up, or a risk of microadenomas or prolactinomas.