Clozapine and the Voice Within: A Case of New-Onset Vocalizations and Obsessive Compulsive Symptoms

Background: Treatment-resistant schizophrenia is the occurrence of delusions or hallucinations despite two antipsychotic drug attempts. Clozapine, an FDA-approved atypical antipsychotic, is reserved for such a case due to its efficacy but is handicapped by a wide array of side effects like sedation, agranulocytosis, seizures, metabolic syndrome, and neuroleptic malignant syndrome. Interestingly, clozapine has also been associated with the development or worsening of obsessive-compulsive symptoms (OCS) in up to 38.2% of patients, purportedly a byproduct of its serotonin 5-HT2A and 5-HT2C receptor antagonism. By comparison, tic-like vocalizations on clozapine are utterly rare and maybe underreported. Case presentation: We report the case of a 39-year-old man with treatment-resistant schizophrenia and psychogenic polydipsia who exhibited tic-like vocalizations and compulsive behavior upon clozapine initiation and dose escalation. Despite initial therapeutic response, the patient evolved with chronic OCS and vocalization, necessitating adjunctive antipsychotic therapy (Aripiprazole) and close behavioral monitoring. Comprehensive assessment excluded organic causes. Unfortunately, treatment with aripiprazole showed no improvement, and he is being monitored on Clozapine. Conclusion: This report underscores the importance of early detection and tailored treatment of rare neuropsychiatric side effects such as clozapine-induced vocal tics. Clinicians must remain vigilant for such signs to optimize therapeutic benefits in treatment-resistant schizophrenia. Regular screening with rating scales is recommended. Treatments like aripiprazole have shown significant OCS improvement, while adjuncts such as valproic acid, often combined with dose reduction, have also been explored.