Off-label Prescribing of Clozapine and Safety

Clozapine is a unique antipsychotic primarily indicated for treatmentresistant schizophrenia, recurrent suicidal behavior in schizophrenia or schizoaffective disorder, and psychotic disorders in Parkinson’s disease. It is also prescribed off-label in selected patients with mood disorders, personality disorders, or post-traumatic stress disorder. Despite its efficacy, clozapine is underprescribed due to concerns regarding adverse effects, particularly agranulocytosis. This narrative review aims to summarize the reported results regarding the off-label use of clozapine and analyze the potential risks and benefits of these practices. Offlabel prescribing, which involves using medications for unapproved indications, is common in psychiatry due to the insufficient effectiveness of many approved treatments. Clozapine, even at relatively low doses, has shown potential clinical benefits in patients with bipolar disorder, borderline personality disorder, and post-traumatic stress disorder. However, its off-label use remains limited due to safety concerns. The safety concerns associated with clozapine include agranulocytosis, myocarditis, cardiomyopathy, seizures, and metabolic syndrome. The prevention of agranulocytosis, a severe reduction in white blood cells, requires regular monitoring of blood counts. Myocarditis and cardiomyopathy necessitate careful cardiological monitoring, especially during the first month of treatment. Seizures can occur, particularly at higher doses, and metabolic syndrome, including weight gain, diabetes, and hyperlipidemia, requires ongoing management. Other adverse effects such as constipation, hypersalivation, and sedation can also impact patient compliance and quality of life. Despite these risks, with careful patient selection, individualized dosing, and continuous monitoring, the therapeutic potential of clozapine in off-label indications warrants further exploration in clinical trials. Keywords: Adverse effects, clozapine, mood disorders, off-label prescribing, personality disorders, post-traumatic stress disorder.