Clozapine-related seizures.
Clozapine is an atypical antipsychotic drug with minimal extrapyramidal toxicity recently approved by the Food and Drug Administration for hard-to-treat schizophrenic patients. We reviewed information on 1,418 patients treated with clozapine in the United States between 1972 and 1988. Forty-one of 1,418 (2.8%) patients had generalized tonic-clonic seizures during treatment with clozapine. Life-table analysis predicts a cumulative 10% risk of seizures after 3.8 years of treatment. Clozapine-related seizures appear to be dose-related. High-dose therapy (greater than or equal to 600 mg/day) was associated with a greater risk of seizures (4.4%) than medium (300 to 600 mg/day; 2.7%) or low doses (less than 300 mg/day; 1.0%). Also, rapid upward titration may increase seizure risk. Thirty-one of 41 patients were successfully continued on clozapine despite seizure occurrence, either with reduction of dose or addition of an antiepileptic medication. Recognition and treatment of clozapine-related seizures will become increasingly important as its use grows in the 1990s.
Devinsky
O
O
Department of Neurology, Hospital for Joint Diseases, New York University School of Medicine, NY 10003.
Honigfeld
G
G
Patin
J
J
D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005544:Forecasting; D006801:Humans; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control; D013997:Time Factors
D000927:Anticonvulsants; D003024:Clozapine