Serum Quetiapine Concentration Changes with Concomitant Oxcarbazepine Therapy in a Boy with Autism Spectrum Disorder.

[Author Affiliation]Ian R. McGrane. 1 Department of Pharmacy, Shodair Children's Hospital, Helena, Montana.Joshua G. Loveland. 1 Department of Pharmacy, Shodair Children's Hospital, Helena, Montana.Heather J. Zaluski. 2 Department of Psychiatry, Shodair Children's Hospital, Helena, Montana.Keith D. Foster. 2 Department of Psychiatry, Shodair Children's Hospital, Helena, Montana.Address correspondence to: Ian R. McGrane, PharmD, Department of Pharmacy, Shodair Children's Hospital, 2755 Colonial Drive, Helena, MT 59601, E-mail: imcgrane@shodair.orgTo The Editor:Children and adolescents with autism spectrum disorder (ASD) may experience various behavioral disturbances that may not fully respond to nonpharmacologic treatments. Aripiprazole and risperidone are currently the only United States Food and Drug Administration (FDA) approved medications for significant irritability associated with ASD. Because of limited pharmacological treatments for irritability, the antiepileptic medication oxcarbazepine (OXC) has been suggested as a treatment option (Kapetanovic 2007; Douglas et al 2013). OXC is a cytochrome P450 (CYP) 3A4 inducing agent that has potential for drug-drug interactions. We present a case of a young boy with ASD who experienced a drug-drug interaction related to OXC use. To our knowledge, this is the first report demonstrating serum quetiapine (QTP) concentration changes in accordance with OXC dosing changes.Case ReportOur patient was an 8-year-old Caucasian male with ASD, intermittent explosive disorder and a full-scale intelligence quotient (IQ) of 46. He presented for his 13th acute psychiatric admission because of increased aggressive behaviors at home and school. Medications at the time of admission included OXC 450 mg twice daily; clonidine 0.1 mg twice daily; and QTP 200 mg every morning, 200 mg at noon, and 300 mg at bedtime. The patient's history of impulsive and aggressive behaviors resulted in many past psychotropic medication trials that were discontinued for various reasons: Risperidone (weight gain), aripiprazole (lack of efficacy), guanfacine (lack of efficacy), lamotrigine (lack of evidence and efficacy), and bupropion (lack of evidence and possible activation). At the time of admission, drug-drug interactions were noted between OXC and QTP. QTP was initially increased to 300 mg three times daily because of the known drug-drug interaction. Upon reviewing available efficacy data for OXC in treating symptoms of aggression, it was decided to discontinue OXC. In order to avoid cholinergic system rebound effects, OXC was tapered over a two week period. The patient continued to struggle with agitation in the evenings, requiring nearly daily restraint procedures during the 1st week of the OXC taper. These behaviors were largely improved during week 2 of the OXC taper. The patient was discharged two weeks following the discontinuation of OXC with prescriptions for QTP 300 mg three times daily, clonidine 0.1 mg twice daily, and polyethylene glycol 17 g twice daily. Two months following discharge, the patient continued on the same medication regimen with no new or worsened adverse events, no physical aggression, and good attendance at school and medical appointments.Therapeutic drug monitoring of serum QTP trough concentrations was conducted several times throughout the OXC taper and previously in 2013 in the absence of CYP3A4 inducing or inhibiting medications (Fig. 1). All serum QTP troughs were drawn after QTP had reached concentration steady-state (Css) and were quantified at ARUP Laboratories (Salt Lake City, UT). …