Drug-induced stuttering: A comprehensive literature review

Abstract

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 In 55.8% of the episodes of DIS, the offending drug was withdrawn to manage stuttering, which resulted in significant improvement or complete relief of stuttering in all cases.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.

Clozapine-Induced Stuttering: Case Report and Literature Review

“…First This binding profile may at the same time contribute to the special antipsychotic properties of clozapine [5].…”

“…Although it has not been reported commonly in the literature, it is not a marginal adverse effect of medications and can significantly affect quality of life. Moreover, a study of drug-induced stuttering by Nikvarz et al, revealed that, in 55.8 % of cases, the implicated drug was withdrawn to manage the stuttering, resulting is significant improvement or complete relief of the stuttering in all cases [5,7].…”

“…According to Nikvarz and coll., The low level of Extrapyramidal sides effects (EPS) with clozapine may be related to the special receptor-binding profile of this medication: during treatment with therapeutically high doses, the level of D2 receptor blockade is too low (40% to 50% occupancy by positron emission tomography) to induce Extrapyramidal sides effects, and the D1 receptor blockade (also 40% to 50% occupancy) has a lower EPS potential than D2 blockade. This binding profile may at the same time contribute to the special antipsychotic properties of clozapine 5 .…”

Acquired Stuttering in Parkinson's Disease

“…11 Involvement of the basal ganglia circuits has also been associated with onset of acquired neurogenic stuttering following traumatic brain injury and drug use. [11][12][13][14] In addition, impairment to the basal ganglia-thalamocortical circuit and associated dopaminergic changes have been suggested as possible neural causes of stuttering. 15,16 In computational modeling of speech production, both low and high levels of dopamine impact on the model's basal ganglia-thalamus-left ventral premotor cortex circuit can result in stuttering moments.…”

“…In patients with stroke‐induced stuttering, brain lesions do not appear to be limited to one specific brain area, 9,10 but have been associated with lesions in the left‐sided cortico‐basal ganglia‐cortical network for speech production 11 . Involvement of the basal ganglia circuits has also been associated with onset of acquired neurogenic stuttering following traumatic brain injury and drug use 11–14 . In addition, impairment to the basal ganglia‐thalamo‐cortical circuit and associated dopaminergic changes have been suggested as possible neural causes of stuttering 15,16 .…”