title: Systematic Review of Clozapine Cardiotoxicity.
abstract: Clozapine is exceptionally effective in psychotic disorders and can reduce suicidal risk. Nevertheless, its use is limited due to potentially life-threatening adverse effects, including myocarditis and cardiomyopathy. Given their clinical importance, we systematically reviewed research on adverse cardiac effects of clozapine, aiming to improve estimates of their incidence, summarize features supporting their diagnosis, and evaluate proposed monitoring procedures. Incidence of early (≤2 months) myocarditis ranges from <0.1 to 1.0 % and later (3-12 months) cardiomyopathy about 10 times less. Diagnosis rests on relatively nonspecific symptoms, ECG changes, elevated indices of myocardial damage, cardiac MRI findings, and importantly, echocardiographic evidence of developing ventricular failure. Treatment involves stopping clozapine and empirical applications of steroids, diuretics, beta-blockers, and antiangiotensin agents. Mortality averages approximately 25 %. Safety of clozapine reuse remains uncertain. Systematic studies are needed to improve knowledge of the epidemiology, avoidance, early identification, and treatment of these adverse effects, with effective and practicable monitoring protocols.
authors.affiliation: International Consortium for Psychotic and Mood Disorders, McLean Hospital, Belmont, MA, USA. martina.curto@gmail.com.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA. martina.curto@gmail.com.|Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy. martina.curto@gmail.com.
authors.forename: Martina
authors.initials: M
authors.lastname: Curto
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Girardi
authors.affiliation: Advanced Molecular Diagnostics Unit, IDI-IRCCS, Rome, Italy.
authors.forename: Luana
authors.initials: L
authors.lastname: Lionetto
authors.affiliation: Department of Cardiology, Sant'Andrea Medical Center, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuseppino M
authors.initials: GM
authors.lastname: Ciavarella
authors.affiliation: NESMOS Department, Sant'Andrea Medical Center, Sapienza University of Rome, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferracuti
authors.affiliation: International Consortium for Psychotic and Mood Disorders, McLean Hospital, Belmont, MA, USA.|Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control; D066126:Cardiotoxicity; D003024:Clozapine / Q000009:adverse effects* / Q000494:pharmacology; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D011618:Psychotic Disorders / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Adverse; Cardiac; Clozapine; Myocarditis; Prevention; Toxicity