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• W2047293224 abstract "Back to table of contents Previous article Next article Letter to the EditorFull AccessTopiramate for Clozapine-Induced SeizuresVICTOR NAVARRO, M.D., ALEX PONS, M.D., ANA ROMERO, PH.D., and MIGUEL BERNARDO, M.D., PH.D., VICTOR NAVARROSearch for more papers by this author, M.D., ALEX PONSSearch for more papers by this author, M.D., ANA ROMEROSearch for more papers by this author, PH.D., and MIGUEL BERNARDOSearch for more papers by this author, M.D., PH.D., Barcelona, SpainPublished Online:1 Jun 2001https://doi.org/10.1176/appi.ajp.158.6.968-aAboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail 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.References1. Wilson WH, Claussen AM: Seizures associated with clozapine treatment in a state hospital. J Clin Psychiatry 1994; 55:184–188Medline, Google Scholar2. Devinsky O, Pacia SV: Seizures during clozapine therapy. J Clin Psychiatry 1994; 55(suppl B):153–156Google Scholar3. Garnett WR: Clinical pharmacology of topiramate: a review. Epilepsia 2000; 41(suppl 1):S61–S65Google Scholar4. Usiskin SI, Nicolson R, Lenane M, Rapoport JL: Gabapentin prophylaxis of clozapine-induced seizures (letter). Am J Psychiatry 2000; 157:482–483Link, Google Scholar FiguresReferencesCited byDetailsCited byJapanese Society of Neuropsychopharmacology: “Guideline for Pharmacological Therapy of Schizophrenia”12 August 2021 | Neuropsychopharmacology Reports, Vol. 41, No. 3Low-dose clozapine-related seizure: A case report and literature reviewWorld Journal of Clinical Cases, Vol. 9, No. 20Efficacy and safety of adjunctive topiramate for schizophrenia: a meta-analysis of randomized controlled trials1 September 2016 | Acta Psychiatrica Scandinavica, Vol. 134, No. 5Medical management of patients on clozapine: A guide for internists23 March 2015 | Journal of Hospital Medicine, Vol. 10, No. 8CNS Drugs, Vol. 29, No. 2The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole- and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide22 May 2015 | Pharmacology, Vol. 95, No. 5-6Use of anticonvulsants as prophylaxis for seizures in patients on clozapine31 August 2013 | Australasian Psychiatry, Vol. 22, No. 1Clinical Schizophrenia & Related Psychoses, Vol. 6, No. 4Clozapine-related EEG changes and seizures: dose and plasma-level relationships16 May 2011 | Therapeutic Advances in Psychopharmacology, Vol. 1, No. 2European Child & Adolescent Psychiatry, Vol. 20, No. 4Topiramate Augmentation in Clozapine-Treated Patients With SchizophreniaJournal of Clinical Psychopharmacology, Vol. 30, No. 6Use of Lamotrigine in a Patient with a Clozapine-Related SeizureJournal of Psychiatric Practice, Vol. 16, No. 2Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 34, No. 3Clozapine-Induced Seizures: Recognition and Treatment1 July 2007 | The Canadian Journal of Psychiatry, Vol. 52, No. 7Clozapine: Current perspectiveIndian Journal of Psychiatry, Vol. 49, No. 4Tourette syndrome8 May 2013NeuroRX, Vol. 3, No. 2Obesity, Vol. 14, No. 1Clinical Neuropharmacology, Vol. 29, No. 1Stress Regulation and Self-MutilationULRICH SACHSSE, M.D., SUSANNE VON DER HEYDE, M.D., and GERALD HUETHER, PH.D., 1 April 2002 | American Journal of Psychiatry, Vol. 159, No. 4Serotonin Syndrome and Atypical AntipsychoticsHARPREET S. DUGGAL, M.B.B.S., D.P.M., and JOSEPH FETCHKO, M.D., 1 April 2002 | American Journal of Psychiatry, Vol. 159, No. 4Topiramate for Refractory SchizophreniaRICHARD C. MILLSON, M.D., JAMES A. OWEN, PH.D., GUNTER W. LORBERG, M.D., and LIANE TACKABERRY, B.A., 1 April 2002 | American Journal of Psychiatry, Vol. 159, No. 4Dr. Butler and Colleagues ReplyPAMELA D. BUTLER, PH.D., ISAAC SCHECHTER, PSY.D., VANCE ZEMON, PH.D., STEPHEN G. SCHWARTZ, M.D., VIVIENNE C. GREENSTEIN, PH.D., JAMES GORDON, PH.D., CHARLES E. SCHROEDER, PH.D., and DANIEL C. JAVITT, M.D., PH.D., 1 April 2002 | American Journal of Psychiatry, Vol. 159, No. 4Reactions Weekly, Vol. &NA;, No. 863 Volume 158Issue 6 June 2001Pages 968-a-969 Metrics History Published online 1 June 2001 Published in print 1 June 2001" @default.
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