• Adverse drug reactions
• adverse events
• clozapine
• narrative review
• schizophrenia
• systematic review

• Clozapine/adverse effects
• Clozapine/administration & dosage
• Humans
• Antipsychotic Agents/adverse effects
• Antipsychotic Agents/administration & dosage
• Schizophrenia, Treatment-Resistant/drug therapy
• Meta-Analysis as Topic
• Systematic Reviews as Topic

Drug-induced stuttering (DIS) is a type of neurogenic stuttering (NS). Although DIS has not been reported as frequently as other cases of NS in the literature, it is not a negligible adverse drug reaction (ADR) which can significantly affect the quality of life if not treated. This literature review aims to evaluate the epidemiological and clinical characteristics of DIS and suggests some pathophysiological mechanisms for this ADR. Relevant English-language reports in Google Scholar, PubMed, Web of Science, and Scopus were identified and assessed without time restriction. Finally, a total of 62 reports were included. Twenty-seven drugs caused 86 episodes of stuttering in 82 cases. The most episodes of DIS were related to antipsychotic drugs (57%), mostly including clozapine, followed by central nervous system agents (11.6%) and anticonvulsant drugs (9.3%). The majority of the cases were male and between the ages of 31 and 40 years. Repetitions were the most frequent core manifestations of DIS. In 55.8% of the episodes of DIS, the offending drug was withdrawn to manage stuttering, which resulted in significant improvement or complete relief of stuttering in all cases. Based on the suggested pathophysiological mechanisms for developmental stuttering and neurotransmitters dysfunctions involved in speech dysfluency, it seems that the abnormalities of several neurotransmitters, especially dopamine and glutamate, in different circuits and areas of the brain, including cortico-basal ganglia-thalamocortical loop and white matter fiber tracts, may be engaged in the pathogenesis of DIS.

• Drug
• Dysfluency
• Dysphemia
• Psychotropics
• Speech
• Stammering

Stuttering is a rare side effect of clozapine. It has been shown to occur in the presence of one or more factors such as abnormal electrophysiological findings and seizures, extrapyramidal symptoms, brain pathology, and a family history of stuttering. Few case reports have documented the occurrence of clozapine-induced stuttering in the absence of these risk factors.

A 29-year-old African male on clozapine for treatment-resistant schizophrenia presented with stuttering at a dosage of 400 mg/day that resolved with dose reduction. Electroencephalogram findings were normal, and there was no clinical evidence of seizures. The patient had no prior history or family history of stuttering, had a normal neurological examination, and showed no signs of extrapyramidal symptoms.

Clinicians ought to be aware of stuttering as a side effect of clozapine, even in the absence of known risk factors. Further research should investigate the pathophysiology of clozapine-induced stuttering.

• Case report
• Clozapine
• Risk factor
• Stuttering

• Adverse event
• Vigibase
• data
• drug
• pharmacovigilance
• stuttering

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.

• clozapine
• speech dysfluency
• stuttering

• Adverse-effects
• Articulation
• Atypical antipsychotics
• Phonation
• Risperidone
• Speech

• Adult
• Antipsychotic Agents/administration & dosage
• Antipsychotic Agents/adverse effects
• Clozapine/administration & dosage
• Clozapine/adverse effects
• Depressive Disorder, Major/drug therapy
• Dose-Response Relationship, Drug
• Female
• Humans
• Stuttering/chemically induced
• Treatment Outcome

• antiepileptic
• clozapine
• seizure
• valproate

• Antipsychotic Agents/adverse effects
• Antipsychotic Agents/blood
• Brain/physiopathology
• Clozapine/adverse effects
• Clozapine/blood
• Drug Administration Schedule
• Electroencephalography
• Epilepsy, Tonic-Clonic/chemically induced
• Epilepsy, Tonic-Clonic/diagnosis
• Epilepsy, Tonic-Clonic/therapy
• Female
• Humans
• Middle Aged
• Schizophrenia, Paranoid/drug therapy
• Severity of Illness Index

• Pharmacoepidemiology