No abstract

Many patients with psychiatric conditions undergo bariatric surgery. The Roux-en-Y gastric bypass (RYGB) procedure alters medication pharmacokinetic properties and may have significant impact on drug response. Our report is the first to describe atypical antipsychotic therapeutic drug monitoring in patients who have undergone RYGB. The first patient is a 53-year-old female with a stable psychiatric condition undergoing a laparoscopic RYGB. Her medications prior and following the procedure include bupropion, fluvoxamine, lurasidone, methylphenidate, oxcarbazepine, and verapamil. A concentration steady-state lurasidone concentration obtained prior to the procedure was 20 ng/mL and returned at 8.1 ng/mL, 29 days after surgery. The second patient is a 42-year-old female psychiatric inpatient who had previously undergone an RYGB procedure. Medications on admission included phenytoin, oxcarbazepine, risperidone, and venlafaxine. The patient was believed to be a good candidate for a long-acting antipsychotic and paliperidone was chosen. After concentration-steady-state on 6 mg oral paliperidone, a 23.5-hour trough level was drawn. The patient was noted to be improved on the oral paliperidone, the paliperidone long-acting injection was given, and the patient was discharged. After discharge, the paliperidone concentration returned very low at 1.1 ng/mL. We describe the contributions of drug–drug interactions, medication release mechanisms, and food coadministration that may have affected our therapeutic drug monitoring. Our therapeutic drug monitoring results need to be replicated prior to use in the general population but suggest that oral extended-release drug formulations are particularly poor choices and that nonoral antipsychotic formulations may be preferred in some patients who have undergone RYBG.

No abstract

Aripiprazole, an atypical antipsychotic, is a metabolic substrate for cytochrome P450 (CYP)3A4 and 2D6. Terbinafine, an antifungal agent used for onychomycosis, is a CYP2D6 inhibitor and could theoretically reduce the metabolism of aripiprazole. However, there are no published reports describing this interaction. We present 2 female patients hospitalized in a psychiatric unit who were both taking aripiprazole 15 mg daily and terbinafine 250 mg daily prior to admission. The first patient was a 58-year-old female who was prescribed aripiprazole and terbinafine concomitantly for approximately 5 months prior to admission. A commercial pharmacogenetic testing platform classified this patient as a normal metabolizer for CYP3A4 and 2D6. The first patient's serum trough aripiprazole concentration at steady-state concentration (Css) was 207.5 ng/mL. The second patient was a 43-year-old female who was taking aripiprazole and terbinafine concomitantly for approximately 2 weeks prior to admission who had a Css aripiprazole concentration of 278.9 ng/mL. Aripiprazole has a wide therapeutic range (100 to 350 ng/mL) and a reference dose-related drug concentration of 11.7 (mean) ± 5.6 (SD) ng/mL/mg/d. Our patients had Css aripiprazole concentrations 18% and 59% higher than guideline-supported dose-related drug concentrations. Through the use of therapeutic drug monitoring, pharmacogenetic data, electronic pharmaceutical claims data, and the Drug Interaction Probability Scale, we suggest terbinafine possibly increases aripiprazole concentrations 18% to 59%. Further reports are needed to confirm these findings prior to using this information in clinical practice.