Acute Onset Extrapyramidal Symptoms With Clozapine: A Report of a Rare Case

Clozapine is considered the gold standard for the management of treatment-resistant schizophrenia (TRS) because of its superior efficacy and relatively low risk of extrapyramidal symptoms (EPS). However, rare cases of clozapine-associated EPS have been reported, challenging the widely held belief regarding its minimal propensity to induce movement disorders. We report the case of a 29-year-old female with TRS who developed acute-onset orofacial dyskinesia and marked psychomotor slowing within one week of initiating clozapine at a low dose of 25 mg/day. The patient exhibited involuntary movements involving the lips, tongue, and facial muscles, accompanied by slurred speech, difficulty with mastication and swallowing, and increased social withdrawal. Neurological examination revealed isolated orofacial dyskinesia without associated rigidity, tremor, or autonomic instability. Clozapine was discontinued promptly, and tetrabenazine was initiated, resulting in significant clinical improvement, with the Abnormal Involuntary Movement Scale (AIMS) score decreasing from 20 to 9. Owing to persistent psychotic symptoms and intolerance to clozapine, the patient was subsequently treated with electroconvulsive therapy (ECT). This case underscores that clozapine, despite its well-recognized favorable extrapyramidal safety profile, may rarely precipitate acute EPS even at low doses. Clinicians should remain vigilant during the initiation phase and monitor for atypical movement disorders to enable timely intervention and optimize outcomes in patients with TRS.