Topiramate for Clozapine-Induced Seizures
To the Editor: Clozapine is an antipsychotic that is associated with a higher prevalence of seizures than traditional neuroleptics (1). Several anticonvulsants, including phenytoin, carbamazepine, and valproic acid, have been found to be effective in the treatment of these seizures (2), but certain side effects and pharmacokinetic interactions may limit their prescription in combination with clozapine. Topiramate is a relatively new, but well-documented, antiepileptic drug with a lack of significant pharmacokinetic interactions and a benign side effect profile (3). We report on a young woman who experienced a generalized tonic-clonic seizure while taking clozapine and was successfully treated with topiramate.
Ms. A, age 23, was seen for treatment of paranoid schizophrenia of a year’s evolution. The results of her laboratory tests and brain imaging studies were normal. Her family history did not include mental illness, and she had no personal history of previous seizures or head trauma. During 10 months of follow-up on an outpatient basis, she had received risperidone, up to 6 mg/day, and then olanzapine, up to 10 mg/day; she had experienced a marked weight increase and an evident negative symptom profile. Because of the presence of depressive symptoms, sertraline, 100 mg/day, had also been prescribed. Finally, she had been hospitalized after a suicide attempt.
During hospitalization, without suspension of her treatment with sertraline, treatment with clozapine was initiated instead of olanzapine. The dose was increased by 50 mg every 4 days. During the third week of clozapine treatment, while taking a stable dose of 200 mg/day, which resulted in a favorable clinical response, Ms. A experienced a 4-minute generalized tonic-clonic seizure. An EEG showed bihemispheric epileptiform activity. Since a favorable clinical response had been observed, clozapine treatment was not suspended. Because of the substantial weight gain with previous treatments, it was decided to prescribe topiramate as an anticonvulsive, given that this drug has been reported to reduce weight (3). The initial dose was 50 mg/day and was increased to 200 mg/day. After 6 months of a regimen of clozapine, 200 mg/day, and topiramate, 200 mg/day, Ms. A showed no evidence of recurrent seizures, either clinically or on EEG. Pretreatment and 6-month follow-up body mass indexes were 26.81 and 25.92 kg/m2, respectively.
We describe a schizophrenic patient who had a generalized tonic-clonic seizure with clozapine therapy who was treated successfully with clozapine and topiramate without showing any recurrence of seizures or side effects. As has recently been suggested with gabapentin (4), topiramate should be considered for prophylaxis in patients taking clozapine who are at a greater risk of seizures and for the treatment of clozapine-induced seizures, particularly in patients who have exhibited a satisfactory clinical response to clozapine.
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