Clozapine is an atypical antipsychotic that is useful in treatment-resistant schizophrenia, but its extensive use is limited by severe adverse effects such as agranulocytosis and seizures. In a large study (Devinsky et al., 1991) on 1418 patients treated with clozapine, 2.8% had generalized tonic-clonic seizures and further life-table analysis predicted a cumulative 10% risk of seizures after 3.8 years of treatment. Clozapine-related seizures appeared to be dose-related; seizure risk was 4.4% with dose > 600 mg/day, 2.7% with 300 to 600 mg/day and 1% with <300 mg/day (Devinsky et al., 1991). Also, rapid upward titration appeared to increase risk of seizures.
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