Antipsychotic Prescribing Practices Following Withdrawal of Concomitant Carbamazepine

Abstract

The goal of this study was to examine provider prescribing habits following carbamazepine discontinuation and to assess for the presence of antipsychotic-related adverse drug reactions due to the loss of car-bamazepine-related induction of the cytochrome P450 enzyme (CYP) 3A4 and p-glycoprotein. A retrospective chart review of patient records from January 2006 through December 2007 at the Veterans Affairs (VA) San Diego Healthcare System was done, which focused on the co-prescription of carbamazepine and a second-generation (atypical) antipsychotic (aripiprazole, quetiapine, risperidone) that is significantly affected by CYP3A4/p-glycoprotein induction. The cases in which carbamazepine was discontinued while the antipsychotic was continued during the 2-year time frame were then analyzed further. Data were collected concerning documentation of antipsychotic-related adverse drug reactions that occurred after carbamazepine was discontinued and prescribers' responses to carbamazepine discontinuation. Nine patients were identified who had concomitant prescriptions for carbamazepine and a second-generation antipsychotic and who then discontinued carbamazepine. In only one case did the provider initially decrease the dose of the antipsychotic when carbamazepine was discontinued. Two patients experienced akathisia 3 weeks after carbamazepine was discontinued. Many providers are not adjusting the dose of second-generation antipsychotics after discontinuation of a CYP3A4/p-glycoprotein inducer, placing patients at risk for adverse drug reactions. In addition to provider education, mechanisms need to be integrated into the current prescription processing software to alert providers of kinetic changes related to medication discontinuation. In addition, when discontinuing carbamazepine in patients who are being concomitantly treated with a second-generation antipsychotic that is a CYP3A4/p-glycoprotein substrate, providers should arrange for patient follow-up 2-4 weeks after carbamazepine discontinuation to evaluate patients for antipsychotic-related adverse drug reactions.