A Review of Clinical Advances and Challenges in Clozapine-Induced Myocarditis

Mier Li,1,* Yuncheng Bai,2,* Yanjun Wang,1,* Haoran Xing,1 Yingying Zhang,1 Wenjing Ding,1 Hong Ye,3 Li Ma,1 Weiwei Wang,4 Tianhao Bao1,5 1Department of Science and Education, The Affiliated Mental Health Center of Kunming Medical University, Yunnan Mental Hospital, Kunming, Yunnan Province, 650032, People’s Republic of China; 2Department of Orthopedic Surgery, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan Province, 650032, People’s Republic of China; 3Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China; 4Department of Geriatrics, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China; 5The Second People’s Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe Hani and Yi Autonomous Prefecture, Yunnan Province, 661400, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiwei Wang, Department of Geriatrics, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China, Email [email protected] Tianhao Bao, Department of Science and Education, The Affiliated Mental Health Center of Kunming Medical University, Kunming, Yunnan Province, 650032, People’s Republic of China, Email [email protected]: Currently, the treatment of schizophrenia remains primarily pharmacological, with approximately 30% of patients diagnosed with treatment-resistant schizophrenia (TRS). Clozapine continues to be the first choice treatment for this subgroup of patients. As the preferred treatment, clozapine offers clear advantages in efficacy; however, its complex and troublesome adverse effects pose significant challenges for psychiatrists. Common side effects include granulocytopenia, intestinal obstruction, myocarditis, cardiomyopathy, constipation, and seizures. The first two complications are easier to manage due to the availability of laboratory monitoring, and improved management strategies are now in place in clinical practice. In recent years, clozapine-induced myocarditis (CIM) has gained considerable attention because of its potentially severe outcomes. However, the mechanism behind its lethality remains unclear, and there is no widely accepted consensus or treatment guideline, which complicates the implementation of targeted prevention in clinical practice. This review aims to summarize the clinical manifestations of CIM, explore the underlying mechanisms, and discuss recent advances in monitoring, diagnosis, and treatment, with the goal of offering constructive recommendations for future clinical management.Keywords: clozapine, myocarditis, mechanism, clinical features, monitoring