Seizures from clozapine

The answer is c. (Hardman7 p 408.) Clozapine differs from other neuroleptic agents in that it can induce seizures in nonepileptic patients In patients with a history of epileptic seizures for which they are not receiving treatment, stimulation of seizures can occur following the administration of neuroleptic agents because they lower seizure threshold and cause brain discharge patterns reminiscent of epileptic seizure disorders. 

Another serious side effect of clozapine is a risk of seizures. This mainly occurs at higher doses of the drug, and having a seizure is not necessarily a sufficient reason to stop clozapine permanently. If the clozapine has been especially helpful, an anticonvulsant can be added to protect against further seizures. Valproate (Depakote) may be best in this regard because it not only provides protection from seizures but also may help to relieve some of the symptoms of schizophrenia. Recently, it has become clear that two atypical antipsychotic drugs, clozapine and olanzapine, are associated with an increased risk for the development of type II diabetes. 

Clozapine has also been compared with risperidone in 60 treatment-resistant patients with schizophrenia in India (16). There was clinical improvement (a more than 20% reduction from baseline PANSS scale scores) in 80% of the clozapine-treated patients and 67% of the risperidone-treated patients. The predominant adverse effects with clozapine (n = 30) were tachycardia (77%), hypersalivation (60%), sedation (60%), weight gain (43%), and constipation (30%) one patient had a seizure. The adverse effects of risperidone (n = 30) were constipation (50%), dry mouth (47%), weight gain (43%), akathisia (37%), insomnia (33%), tachycardia (30%), and impotence (27%). The final mean daily doses after 16 weeks of treatment were 343 mg for clozapine and 5.8 mg for risperidone. 

Clozapine, which is associated with higher risk of agranulocytosis and seizures, is indicated (25 mg once or twice daily) only in the management of schizophrenic patients who fail to respond adequately to standard antipsychotic drug treatment. On the other hand, it is relatively free from extrapyramidal side effects such as parkinsonism. Approximately 50% of the administered dose is excreted in the urine and 30% in the feces as inactive demethylated, hydroxylated, and N-oxide derivatives. Clozapine has anticholinergic properties and causes tachycardia, and hence poses a serious risk for a patient with compromised cardiovascular function (see also Table 23). 

---