A 13-year-old boy with autism and LGS with a history of 2 prior epilepsy surgeries and vagus nerve stimulator (VNS) placement presented to our comprehensive epilepsy clinic to transfer care. Epilepsy onset was at 18 months, and he had a history of atonic seizures and generalized tonic-clonic seizures, along with focal seizures with loss of awareness. The etiology of his phenotype was unknown. He underwent a full corpus callosotomy at age 4, left frontal lobe resection at age 7, and VNS placement at age 11 (all at an outside institution). His parents described a semiology of staring and behavioral arrest for 2-3 minutes with oral and/or manual automatisms. These seizures were occurring several times per week. Prior antiseizure medication trials included rufinamide, valproic acid, levetiracetam, topiramate, oxcarbazepine, lamotrigine and lacosamide. At the time of presentation, he was taking 2 ASMs at stable doses over 4 months: Felbamate 24 mg/kg/day and Clobazam 0.5 mg/kg/day.

He met criteria for Autism Spectrum Disorder, co-morbid with severe intellectual disability and associated aggressive and self-harmful behaviors and sleep difficulties. At baseline, he was non-verbal with incontinence, though with full strength and ambulation.

He transitioned to our psychiatry service during a hospitalization several months prior to the initiation of CBD. At that prior hospitalization, he had been increasingly lethargic but also aggressive, in what was thought to be polypharmacy. During that prior admission Bupropion, Pregabalin, and Amantadine were all discontinued. He remained on a complex regimen of psychoactive medications, including Lithium 600 mg qAM, 300 mg qPM and 600 mg qhs, Perphenazine 8 mg TID, Quetiapine 200 mg twice a day and 400 mg qhs, and Trazodone 300 mg qhs. The dose of Lithium- targeted for aggression in a developmentally delayed patient- had been unchanged for over a year with stable and therapeutic lithium levels.

Upon presentation to our epilepsy clinic, we recommended a trial of CBD to improve seizure control and possibly behavior. His psychiatrist agreed to this plan of care. He started CBD at 5 mg/kg/day, divided bid. Due to potential interactions with clobazam, the clobazam dose was simultaneously decreased by 25%.

During the first 2 weeks of treatment, he did well. However, soon after his CBD dose was increased to 10 mg/kg/day as per titration schedule, he began to exhibit symptoms of lethargy, weakness, unsteadiness, and decreased oral intake, prompting an emergency department (ED) evaluation and admission to the hospital. By this point his clobazam had been decreased to 50% of the initial dose. His parents reported that soon after taking the midday doses of medications (lithium, clonidine and felbamate) he would become tired, lethargic, and off balance.

Upon evaluation in the ED, he was afebrile though somnolent. When arousable and more awake he was ataxic compared to baseline. Blood pressure, blood counts, electrolytes, liver enzyme levels, renal function tests, and clobazam levels were all unremarkable. In contrast, the lithium level was notably elevated at 2.4 mmol/L (compared to his historic baseline of 1 -1.3 mmol/L). Psychiatry and neurology were consulted. Lithium was stopped, and midday doses of clonidine and felbamate were held. He was placed NPO and on twice maintenance intravenous fluids with serial checks of lithium levels and monitoring of urine output, with a targeted goal of 1-2 ml/kg/hr. Lithium levels declined over the subsequent 48 hours, and his mental status improved. He was monitored for 3 days during which time he gradually returned to baseline and remained seizure-free. His parents reported improved behavior and requested that he remain off lithium. On the day of discharge, his lithium level was 0.6 mmol/L, and he remained on perphenazine, quetiapine, and trazodone.

Nearly one year after admission, he continues on CBD 10 mg/kg/day, half dose clobazam, home felbamate dose, and remains off lithium. Parents have not detected any seizures, and they note that his behavior is improved.