Clozapine-induced seizures

Clozapine remains one of the leading antipsychotic medications to date. It is a first-line drug in treatment-resistant schizophrenia, tardive dyskinesia in patients previously receiving other antipsychotics as well as in patients with aggressive behaviour. Furthermore, clozapine therapy significantly reduces suicidal behaviour and improves the quality of life. Clozapine-related adverse effects include, among other things, agranulocytosis and granulocytopenia, seizures, myocarditis, metabolic syndrome, sialorrhea, sedation. Despite the numerous adverse effects, the mortality among clozapine-treated patients is lower compared to the overall schizophrenic population. Clozapine lowers the seizure threshold and induces seizures. The risk of seizures is dose-dependent and is approximately 4.4%. Tonic-clonic seizures are most commonly reported, followed by myoclonus and atonic seizures. Difficulty in speaking, myoclonus and falls during atonic seizures may be signs of approaching tonic-clonic seizures. Although the monitoring of clozapine serum levels and electroencephalography were shown to be an effective aid in the therapy, they failed to show efficacy in assessing the risk of seizures. In the case of combination therapy, potential interactions between clozapine and a number of other drugs should be considered. When a first seizure occurs, it is recommended that the dosage of clozapine be reduced. If a second seizure occurs, an anticonvulsant drug should be initiated. Valproic acid and lamotrigine are first-line anticonvulsants for clozapine-induced seizures. It is worth noting that there is no metabolic interaction between lamotrigine and clozapine and that lamotrigine potentiates the antipsychotic effects of clozapine. Gradual increasing and decreasing clozapine doses is recommended for the prevention of seizures.