First case report links zonisamide to homicidal ideation in epilepsy patient

IntroductionCerebral cavernous malformations (CCMs) are vascular lesions that can cause focal epilepsy due to local hemosiderin deposition, gliosis, and cortical irritation. Epileptic seizures attributable to CCMs contribute significantly to morbidity and often require long-term management with antiseizure medications (ASMs), but the psychiatric side effect profiles of ASMs remain underreported in the literature.Case reportHerein, we present a case report of a patient with homicidal ideation following zonisamide use and uptitration following an Epilepsy Monitoring Unit (EMU) stay. Detailed is his hospitalization for this side effect and transition to another ASM so that he could return to a normal life outside the hospital.MethodsTo contextualize this case, a literature review was conducted using PubMed from 1990 to 2026 using combinations of the terms “zonisamide,” “antiepileptic drugs,” “homicidal ideation,” and “psychiatric adverse effects.” Relevant articles were manually reviewed and no prior cases explicitly describing homicidal ideation associated with zonisamide were identified.ConclusionHomicidal ideation should be contextualized within a spectrum of ASM-associated psychiatric adverse effects (PAEs). Zonisamide may have contributed to symptom emergence in a susceptible individual within a multifactorial neuropsychiatric context. To our knowledge, this is the first case report explicitly documenting homicidal ideation as an adverse event of zonisamide.