Possible inhibitory effects of terbinafine on aripiprazole metabolism: Two case reports.

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.

Successful bilateral electroconvulsive therapy in a patient with a seizure disorder taking levetiracetam, lorazepam, and zonisamide: A case report.

Electroconvulsive therapy (ECT) may be considered for treatment of severe, treatment-resistant, and emergent depression associated with MDD or bipolar disorder. Patients with epilepsy usually take medications that raise the seizure threshold, which poses challenges during ECT. We report a 66-year-old male with epilepsy taking levetiracetam extended-release (XR), lorazepam, and zonisamide requiring ECT for severe MDD. After literature review, the XR form of levetiracetam was changed to higher doses of the immediate-release (IR) formulation, and zonisamide was discontinued 2 days prior to ECT in the hospital and was resumed when the patient underwent outpatient continuation ECT. The patient was treated to remission after receiving 8 acute bilateral ECT treatments before being transitioned to continuation ECT. We provide a brief review of medication management of antiepileptic drugs and other medications that increase the seizure threshold during ECT. To our knowledge, this is the first reported case describing the management of levetiracetam, lorazepam, and zonisamide concomitantly during ECT. Our case suggests that utilizing the IR formulation of levetiracetam, administering the evening dose early the day prior to the procedure, and temporarily discontinuing zonisamide prior to bilateral ECT is effective for the treatment of severe MDD while maintaining seizure prophylaxis.

Roux-en-Y Gastric Bypass and Antipsychotic Therapeutic Drug Monitoring: Two Cases.

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.

Worsening Choreoathetosis in Huntington's Disease with Fluoxetine, Lisdexamfetamine, and Melatonin: A Case Report.

Cognitive, affective, and sleep disturbances can be found in patients with Huntington's disease (HD), and medications used to treat these HD-related sequela can also impact HD-related movement disorders. We present the case of a 52-year-old Caucasian man with previously undiagnosed HD who exhibited significant choreoathetoid movements that improved with discontinuation of fluoxetine and lisdexamfetamine upon hospital admission. Following diagnosis of HD through genetic testing, he was administered 5mg of oral melatonin on two consecutive evenings, which resulted in worsening choreoathetosis. We calculated Naranjo adverse event scores of 5, 5, and 2 for fluoxetine, lisdexamfetamine, and melatonin, respectively, based on our assessment, review of outpatient medical records, and available literature. We review the literature surrounding these possible adverse drug events and their mechanisms regarding dopaminergic modulation in early-middle stages of HD. Our report indicates that caution should be exercised when initiating psychostimulants, fluoxetine, and melatonin in patients with early-middle stage HD. Screening for HD might be warranted for patients who develop choreoathetosis after initiation of the aforementioned medications. We recommend ascertaining baseline level of chorea before initiating these medications in patients with known HD and closely monitoring for exacerbation during therapy.