Background Treatment-resistant schizophrenia is defined by persistent delusions or hallucinations following failed trials of two other antipsychotic medications. Clozapine, an atypical antipsychotic medication approved by the FDA, is often the medication of choice in such challenging cases due to its proven efficacy. Its use is, however, tempered by a myriad of side effects which range from sedation, agranulocytosis, seizures, metabolic syndrome, and neuroleptic malignant syndrome. Mahendran R et. al particularly talked about clozapine being involved in the emergence or worsening of obsessive-compulsive symptoms (OCS) in up to 38.2% of patients, which is a side effect due to antagonism of the serotonin receptors 5-HT2A and 5-HT2C. On the other hand, tic-like vocalizations associated with clozapine are extremely rare and perhaps underreported.

Case Presentation We describe a 39-year-old man with treatment-resistant schizophrenia and psychogenic polydipsia and Wolfe-Parkinson-White Syndrome s/p ablation, who, following the initiation and gradual titration of clozapine treatment, developed tic-like vocalizations and compulsive behaviors (excessive washing of face resulting in abrasions on forehead). While Clozapine was initially helpful in reducing some symptoms, the patient progressively developed treatment-emergent obsessive-compulsive behaviors and repetitive vocalizations. To manage these new challenges, a second antipsychotic medication, aripiprazole, was introduced in his regimen alongside intensive behavioral monitoring. Despite this, the vocalizations continued. A comprehensive evaluation ruled out any organic cause. This case illustrates the complex and treatment-resistant nature of these symptoms.

Discussion Although clozapine-induced vocalizations are uncommon, they are a significant neuropsychiatric side effect that should be recognized by clinicians. Czapliński et al. described that vocalizations are characterized by sudden, repetitive, and stereotyped sounds, most commonly occurring hand in hand with compulsive behaviors or other movement symptoms. David D. Kim et al. explained in a systematic review that the response to adjunct therapies such as aripiprazole and behavior therapy can be helpful, and individualized treatment strategies are crucial. This case brings to light the importance of early identification and individualized treatment plans for atypical but meaningful side effects like clozapine-induced vocalizations. While clozapine is the treatment standard for treatment-resistant schizophrenia, its potential to cause or reveal obsessive-compulsive behavior and unusual vocalizations must be monitored carefully and addressed individually to maximize benefit with minimal risk of adverse effect.