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First case report links zonisamide to homicidal ideation in epilepsy patientFirst case report links zonisamide to homicidal thoughts in an epilepsy patient

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Key Takeaway
Consider homicidal ideation as a rare psychiatric adverse effect of zonisamide, especially in vulnerable patients.

This case report and literature review describes a patient with cerebral cavernous malformations and epilepsy who developed homicidal ideation during zonisamide uptitration in an Epilepsy Monitoring Unit. The symptom emerged in a susceptible individual and resolved after transitioning to another antiseizure medication. The authors note that no prior cases explicitly describing homicidal ideation associated with zonisamide were identified, making this the first such report.

The review contextualizes homicidal ideation within a spectrum of antiseizure medication-associated psychiatric adverse effects. The authors emphasize that zonisamide may have contributed to symptom emergence in a multifactorial neuropsychiatric context, but caution against overstating causality. They highlight the need for clinicians to monitor for psychiatric adverse effects when prescribing zonisamide.

Limitations include the single-case design and lack of prior reports. The practice relevance is that homicidal ideation should be considered as a potential, albeit rare, adverse effect of zonisamide, particularly in patients with underlying neuropsychiatric vulnerability. Clinicians should remain vigilant and consider transitioning to another antiseizure medication if such symptoms arise.

A patient in an epilepsy monitoring unit began experiencing thoughts of harming others after starting zonisamide. These thoughts appeared as the doctor increased the dose of the medication. The team eventually switched the patient to a different antiseizure drug to manage the situation. This specific event was not reported in previous medical records, making this case unique. The patient had a background that made them more vulnerable to these mental health changes. Doctors noted that this reaction happened within a complex mix of factors affecting brain chemistry. The patient did not stop taking the medication immediately, but the team moved to a safer alternative. This situation shows how some people react differently to standard treatments for seizures. It is important to remember that this is a rare occurrence and not something that happens to everyone. However, any new or worsening mental health symptoms need immediate attention from a medical professional. Patients should tell their doctor right away if they feel angry or have thoughts of hurting others. Early detection helps prevent harm and ensures the right treatment plan is in place.

What this means for you:
Doctors should watch for rare mental health changes like homicidal thoughts in patients taking zonisamide.

Study Details

Study typeSystematic review
EvidenceLevel 1
PublishedJun 2026
View Original Abstract ↓
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.
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