Stuttering associated with clozapine use: a case report

Introduction: Clozapine remains the most effective antipsychotic for treatment-resistant schizophrenia (TRS), yet its clinical use is often limited by serious adverse effects.These include agranulocytosis, seizures, myocarditis and metabolic disturbances.Rare side effects, such as stuttering, may go unrecognized despite significantly impacting patients’ quality of life.Stuttering is defined as a disturbance in the fluency and time patterning of speech and may be developmental or acquired.Drug-induced stuttering is a form of acquired neurogenic stuttering and has been linked to several psychotropics, including clozapine [1].While clozapine-induced stuttering is typically reported alongside EEG abnormalities, seizures or extrapyramidal symptoms, some cases occur without such findings.Here, we describe a patient with no neurological or structural abnormalities who developed persistent stuttering after clozapine initiation.

Case Presentation: A 55-year-old married man, diagnosed with chronic paranoid schizophrenia in 2011, was referred in 2025 because of persistent social withdrawal and long-standing fluency disorder.In May 2013, after failing to respond to previous treatments the patient was diagnosed with TRS and started on clozapine therapy titrated to 250 mg/day.He showed significant improvement in psychotic symptoms and suicidal ideation. However, within weeks of clozapine initiation, he developed speech difficulties that progressed to persistent stuttering.Despite voicing concern during follow-ups, the symptom was attributed to sedation. By 2015, the stuttering had stabilized.A thorough psychiatric and neurological workup was performed in 2025 to evaluate the origin of the stuttering symptoms. Over the following decade, he remained psychiatrically stable on clozapine with no seizures, motor side effects or cognitive impairment.EEG and MRI findings were normal.The patient had no history of head injury, substance use or stutter in the family.Treatment compliance and insight were high.At assessment, the Positive Symptom Scale (SAPS) and Negative Symptom Scale (SANS) scores were 4 and 16, respectively. The Clinical Global Impression (CGI) severity score was 3, the CGI-Adverse Effects score was 3. The measured clozapine plasma level was 496.2 ng/mL (at dose of 250 mg/day).This level is within the established therapeutic range (typically 350-600 ng/mL).Persistent fluency impairment suggests that stuttering is not related to high-dose clozapine.The clinical presentation, combined with the temporal relationship to clozapine initiation and the lack of alternative explanations, supports the diagnosis of clozapine-associated stuttering, despite the patient's early reports.

Discussion: This case illustrates clozapine-induced stuttering in a patient with no EEG/MRI abnormalities or identifiable neurological risk factors.It contributes to growing evidence that this side effect can occur independently of seizures or extrapyramidal symptoms.The pathophysiology is unclear but may involve functional dysregulation in speech-related neural circuits, such as the prefrontal cortex, basal ganglia and supplementary motor areas[2].Though dose reduction has improved stuttering in some reports, maintaining clozapine was prioritized here due to past treatment resistance and sustained remission[3].This underscores the importance of individualized treatment planning.Informed consent was obtained from the patient for publication.

Conclusion: Clinicians should consider stuttering a potential clozapine side effect, particularly when no other etiological explanation is evident.Increased awareness may lead to earlier recognition, patient education and targeted interventions such as speech therapy or gradual titration strategies.Further research is needed to clarify the neurobiological basis and management strategies for clozapine-induced stuttering.

References:

[1]. Jaballah, F., Aissa, A., Ouali, U., Zgueb, Y., & Jomli, R. (2023). Clozapine-Induced Stuttering: Case Report and Literature Review. Pharmacopsychiatry, 56(06), 240-243. [2]. De Bartolomeis, A., Buonaguro, E. F., Latte, G., Rossi, R., Marmo, F., Iasevoli, F., & Tomasetti, C. (2017). Immediate-early genes modulation by antipsychotics: translational implications for a putative gateway to drug-induced long-term brain changes. Frontiers in behavioral neuroscience, 11, 240. [3]. Nagendrappa, S., Sreeraj, V. S., & Venkatasubramanian, G. (2019). "I Stopped Hearing Voices, Started to Stutter"-A Case of Clozapine-Induced Stuttering. Indian Journal of Psychological Medicine, 41(1), 97-98.

No conflict of interest