title: Potential bias in testing for hyperprolactinemia and pituitary tumors in risperidone-treated patients: a claims-based study.
abstract: BACKGROUND
  A reporting association of risperidone with pituitary tumors has been observed. Because such tumors are highly prevalent, there may be other reasons why they were revealed in association with risperidone treatment. We assessed two potential explanations: disproportionately more prolactin assessment and head/brain imaging in risperidone-treated patients vs patients treated with other antipsychotics.
  
  
  METHODS
  Treatment episodes with risperidone, clozapine, olanzapine, quetiapine, ziprasidone, aripiprazole, haloperidol, perphenazine and 'other typical' antipsychotics were identified in two databases (large commercial, Medicaid). Comparisons used proportional hazards regression to determine whether prolactin testing was disproportionate with risperidone, regardless of prior potentially prolactin-related adverse events (PPAEs). Logistic regression determined whether magnetic resonance imaging (MRI)/computed tomography (CT) were disproportionate in risperidone-treated patients vs other patients, regardless of hyperprolactinemia or PPAEs. In each regression, the 'other typical' antipsychotic category served as the comparator. Regression models controlled for age, gender, and other factors.
  
  
  RESULTS
  Altogether, 197,926 treatment episodes were analyzed (63,878 risperidone). Among patients with or without preceding PPAEs, risperidone treatment was associated with a significantly greater likelihood of prolactin assessment (hazard ratio (HR) 1.34, 95% confidence interval (CI) = 1.09 to 1.66, p = 0.007). Among patients with hyperprolactinemia or PPAEs, those treated with risperidone (odds ratio (OR) 1.66, 95% CI 1.23 to 2.23, p = 0.001) or ziprasidone (OR 1.66, 95% CI 1.06 to 2.62, p = 0.028) had a higher likelihood of MRI/CT.
  
  
  CONCLUSIONS
  Risperidone-treated patients are more likely to undergo prolactin assessment regardless of prior PPAEs, and more likely to undergo MRI/CT in association with hyperprolactinemia or PPAEs. Thus, a predisposition for more evaluations in risperidone-treated patients may contribute to disproportionate identification and reporting of prevalent pituitary adenoma.
authors.affiliation: HECON Associates Inc,, 9833 Whetstone Drive, Montgomery Village, MD 20886, USA. frank_gianfrancesco@heconassoc.com
authors.forename: Frank D
authors.initials: FD
authors.lastname: Gianfrancesco
authors.forename: Gahan
authors.initials: G
authors.lastname: Pandina
authors.forename: Ramy
authors.initials: R
authors.lastname: Mahmoud
authors.forename: Jasmanda
authors.initials: J
authors.lastname: Wu
authors.forename: Ruey H
authors.initials: RH
authors.lastname: Wang