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Psychosis following initiation of zonisamide.

“Ms. A” was a 50-year-old Caucasian female with a 41year history of seizures refractory to multiple antiepileptic regimens, mild mental retardation, and no previous psychiatric history. Phenytoin, primidone, and vagal nerve stimulator placement 30 months before her admission led to improved seizure control, with no apparent psychiatric symptoms. Eight months before hospitalization, phenytoin was discontinued and zonisamide was added, titrated to 300 mg/day with subsequent variation between 200 mg/day to 400 mg/day. Ms. A’s family reported that within two to three weeks of starting zonisamide, she became hostile, irritable, and isolative. Over six months, her family relationships worsened as these behaviors continued. Two weeks before admission, Ms. A was observed in an emergency room as being belligerent, paranoid, and reporting auditory and visual hallucinations. She had called police about family, refused to bathe, perseverated about medication, and limited eating and drinking. She was instructed to discontinue zonisamide. Upon psychiatric admission, valproic acid was started for seizure control; primidone and vagal nerve stimulation continued. Ms. A received olanzapine, which was increased over four days to 15 mg qhs. During her initial three inpatient days, she was agitated, paranoid, intrusive, and periodically combative, requiring seclusion. Ms. A’s psychosis gradually resolved over four weeks. Upon discharge she displayed perseveration and mild irritability, but demonstrated no paranoia, delusions, or hallucinations. Discharge medications were olanzapine, primidone, and valproic acid.