Clozapine-Induced Stuttering and Seizures

Mr. A, a 28-year-old man who had been diagnosed with paranoid schizophrenia of 8 years’ duration, was treated with clozapine because treatment resistance. An EEG performed when he was receiving 150 mg/day of clozapine showed bilateral frontotemporal slowing (left more than right), generalized nonparoxysmal sharp and slow waves, and a photic convulsive response. Because Mr. A was having a good response to clozapine, it was decided to continue giving him clozapine under close supervision. However, at a clozapine dose of 300 mg/day, he developed stuttering, which worsened with further increases.

At that point, we were unaware of any association between clozapine and stuttering. It was only when Mr. A developed severe stuttering and subsequently had a generalized tonic-clonic seizure when he was taking 425 mg/day of clozapine that we considered that the stuttering might be related to clozapine-induced seizures. We then performed a literature search on PubMed using the key words “clozapine” and “stuttering,” which yielded three related reports (1–3). Our observation of clozapine-induced stuttering was supported by the dramatic improvement in Mr. A’s stuttering after his clozapine dose was reduced to 200 mg/day. Concurrently, we started treatment with valproate and titrated the dose up to 800 mg/day.

An EEG taken a day after Mr. A’s generalized seizure showed generalized nonparoxysmal slowing and a photic convulsive response in posterior regions of the brain. The association between stuttering and seizures was further bolstered by the fact that Mr. A did not have a reemergence of stuttering when his dose of clozapine was again increased to 300 mg/day (the dose at which stuttering had initially appeared) while he was also taking valproate. A normal EEG corroborated this evidence.