Prolonged Serotonergic Symptoms in a Pediatric Patient: Suspected Interaction Between Prescription Medications and Kava Supplement

Abstract

Kava (Piper methysticum) is consumed for a variety of medical and cultural purposes. It is reported to have anxiolytic, muscle relaxant, local anesthetic, and sedative properties. The unregulated use of kava has grown more popular in the United States for a variety of indications and often in combination with traditional pharmaceuticals. A review of existing literature revealed no prior reports of adverse effects from concurrent use of kava and serotonergic agents. We present a pediatric patient who developed prolonged serotonin syndrome after daily use of kava while transitioning from duloxetine to venlafaxine. A 16-year-old female patient presented to the emergency department with complaints of facial twitching, palpitations, increased anxiety, restlessness, and diaphoresis. Her vital signs were remarkable for tachycardia. Physical examination revealed hyperreflexia and involuntary muscle movements. Her home medications included duloxetine, venlafaxine, aripiprazole, and zolpidem. Over the prior month, the patient had begun taking two different kava preparations for her anxiety. Symptoms were refractory to typical escalating doses of cyproheptadine (18 mg within the first 24 hours) and benzodiazepines (6 mg within the first 24 hours), despite the patient being benzodiazepine naïve. The patient required treatment for 72 hours following discontinuation of serotonergic agents. This case highlights the importance of pharmacovigilance for significant interactions between herbal products and psychotropics. Several kavalactones have demonstrated significant CYP2D6 and monoamine oxidase inhibition, which in this case may have led to higher neuronal cleft serotonin-norepinephrine reuptake inhibitor drug and active metabolite concentrations. Clinicians should advise patients to limit the use of kava supplements while taking certain prescribed serotonergic medications.

Keywords: cyproheptadine; drug-drug interaction; duloxetine; kava kava; p450 2d6; piper methysticum; serotonin syndrome; venlafaxine.