A case of clozapine-induced tonic-clonic seizures managed with valproate: implications for clinical care

We describe a case of clozapine-induced seizures in a patient with treatment-resistant schizophrenia. She had previously been treated unsuccessfully with a number of atypical antipsychotic medications, before she was eventually started on clozapine. She experienced two separate episodes of observed fits whilst on an initial daily dose of 125 mg and, subsequently, on a daily dose of 237.5 mg. Following discontinuation of clozapine, she was rechallenged and again was observed to have seizures. Appropriate investigations ruled out any organic cause of the fits and clozapine was successfully restarted, together with sodium valproate. By the time of treatment stabilization, the patient had not experienced any further fits. These findings suggest that clozapine-induced seizures can be successfully treated, that gradual dose titration can reduce the likelihood of further episodes of seizures and that concomitant use of a suitable mood stabilizer/anti-epileptic medication can improve the outcome of treatment-resistant schizophrenia. Furthermore, the concomitant use of fluoxetine and clozapine is discouraged, with citalopram suggested as a suitable antidepressant in those depressed patients receiving clozapine.