Extreme Hypertriglyceridemia Following Clozapine Treatment: A Case of Twenty-Fold Increase

Abstract

Clozapine is a second-generation antipsychotic agent with established efficacy in patients with treatment-resistant schizophrenia. Among the most frequently reported adverse effects of clozapine are components of the metabolic syndrome, including central obesity, insulin resistance, impaired glucose metabolism, dyslipidemia and elevated blood pressure. It has been shown in several studies that clozapine use is associated with clinically relevant increases in serum triglyceride (TG) levels, ranging from 35% to nearly 100% over long-term treatment. In this case, an approximately twenty-fold increase in serum TG levels was observed following the initiation of clozapine therapy, rising from 73 mg/dL t o 1686 mg/dL. Prior to clozapine administration, the patient was undergoing treatment for hyperlipidemia, and lipid parameters remained within normal limits. After initiating pharmacological treatment for hypertriglyceridemia, including statins, fibrates, and omega-3 fatty acids, clozapine was gradually tapered and replaced with aripiprazole. Subsequently, serum TG levels decreased to 604 mg/dL over a period of several months. The marked elevation in TG levels observed in our patient was considered to be associated with the patient's pre-existing history of hyperlipidemia. When evaluated in the light of the data obtained from this case, it can be suggested that the rate of lipid increase may be higher than expected in patients wit h a history of hyperlipidemia who are candidates for clozapine treatment; therefore, it may be recommended that lipid levels be monitored on a monthly basis during the early phase of treatment and at periodic intervals thereafter in such individuals. © 2025, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.