Epilepsy‐Related Psychosis in Drug‐Resistant Epilepsy With Nonconvulsive Status Epilepticus and Difficult Antipsychotic Titration: A Case Report

INTRODUCTION: Psychosis in epilepsy may be difficult to diagnose when altered consciousness, antiseizure medication changes, and psychotropic adverse effects coexist. CASE PRESENTATION: We report a man in his late 50s with longstanding drug-resistant epilepsy and recurrent psychosis. His documented convulsive seizures were classified as tonic-clonic seizures of unknown onset; epilepsy type and etiology could not be assigned. During admission for medication adjustment, reduced responsiveness and fluctuating alertness developed. EEG showed generalized rhythmic epileptiform activity at 2-3 Hz with evolution, and EEG/awareness improved after intravenous diazepam before fosphenytoin was introduced, supporting nonconvulsive status epilepticus. After treatment with fosphenytoin/phenytoin and improvement of nonconvulsive status epilepticus (NCSE), continuous EEG monitoring was performed to assess the phenytoin response and monitor electrographic recurrence. Serum antiseizure medication levels measured at multiple time points, together with MRI, blood tests, and the clinical course, made overt intoxication, acute structural or metabolic disease, and dementia with Lewy bodies less likely. After epileptiform activity attenuated and antipsychotics were withdrawn, psychosis re-emerged without EEG evidence of ongoing status epilepticus. The course was interpreted as interictal psychosis with a possible alternative psychosis component. Aripiprazole improved psychosis but caused akathisia/dyskinesia, requiring cross-titration to brexpiprazole. Levetiracetam reduction was limited by worsening EEG abnormalities. DISCUSSION AND CONCLUSION: This case emphasizes the need for a low threshold for EEG, structured diagnostic reasoning, and careful monitoring of pharmacokinetic interactions when treating psychosis in drug-resistant epilepsy.