Clozapine-Induced Microseizures, Orofacial Dyskinesia, and Speech Dysfluency in an Adolescent with Treatment Resistant Early Onset Schizophrenia on Concurrent Lithium Therapy

Abstract

Clozapine is an atypical antipsychotic used in the treatment of refractory schizophrenia. It has a well-known side effect profile, including agranulocytosis, decreased seizure threshold, and tardive dyskinesia. In addition, numerous case reports have described clozapine-induced stuttering in adults. However, there has been only one previous case report describing it in the adolescent population. In addition, concurrent lithium therapy has been shown to enhance the neurotoxic effects of antipsychotics and lower the seizure threshold. Here, we report on the development of clozapine-induced microseizures, orofacial dyskinesia, and stuttering in a 17-year-old adolescent male with treatment of refractory early onset schizophrenia on clozapine and concurrent lithium therapy. The patient's symptoms of schizophrenia responded well to the clozapine regimen. However, with the escalating dose of clozapine, the patient developed speech dysfluency in the form of stuttering and perioral twitching. An electroencephalogram confirmed seizure activity. Due to similarities with tardive dyskinesia, symptoms of microseizures induced by atypical antipsychotics may not be accurately diagnosed. A multidisciplinary treatment of speech dysfluency is of particular importance in the adolescent schizophrenic patients, who are expected to have longer duration of lifetime exposure to antipsychotics and in whom peer group interaction is crucial for normal personal and social development.

“I Stopped Hearing Voices, Started to Stutter” - A Case of Clozapine-Induced Stuttering

“…[8] A few studies on clozapine-induced stuttering suggest an association between the stuttering and a seizure-like activity in EEG and improvement with antiepileptics. [9] However, our patient did not have any seizures clinically or electrophysiologically, which was also the case with many other cases reported earlier. [2] Hence, the exact mechanism needs further systematic evaluation.…”

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

“… 412 While it is overall considered to be safe, concomitant treatment with clozapine and lithium can markedly decrease the seizure threshold. 151 , 417 , 418 …”

Drug-induced stuttering: A comprehensive literature review

“…Regarding the other likely mechanisms of clozapine-induced stuttering, it has been suggested that stuttering may be a manifestation of seizure. Clozapine-induced stuttering was associated with seizure or EEG abnormalities without typical symptoms of seizure in nine out of 30 case reports[ 12 , 25 , 59 , 60 , 62 - 66 ], and stuttering was significantly improved or completely relieved by addition of sodium valproate and the dose reduction of clozapine in five cases[ 12 , 59 , 62 , 64 , 66 ]. In the other four cases[ 25 , 60 , 63 , 65 ], anticonvulsant drugs were not tried, but discontinuation or dose reduction of clozapine resulted in complete relief of stuttering in three cases[ 60 , 63 , 65 ].…”

“…After the addition of sodium valproate, the patient had no seizure, but stuttering did not improve. It is worth mentioning that three cases had stuttering with both movement disorders and EEG abnormalities[ 60 , 62 , 63 ], which may demonstrate that some movement disorders induced by clozapine may be due to the epileptiform activity in the brain rather than EPS.…”