Pathogenesis and management of Brugada syndrome in schizophrenia: A scoping review

Abstract

Context: Excess cardiovascular morbidity and an increased prevalence of sudden cardiac death (SCD) contributes to premature mortality in schizophrenia. Brugada syndrome (BrS) is an important but underrecognized cause of SCD. It is more commonly seen in schizophrenia than in general population controls.

Methods: We conducted a scoping review to describe the pathogenesis of BrS in schizophrenia and to identify the psychotropic medications that increase the risk of unmasking BrS and associated ventricular arrhythmias resulting in SCD.

Findings: Schizophrenia and BrS share similar calcium channel abnormalities, which may result in aberrant myocardial conductivity. It remains uncertain if there is a genetic pre-disposition for BrS in a subset of patients with schizophrenia. However, the unmasking of Brugada ECG patterns with the use of certain antipsychotics and antidepressants increases the risk of precipitating SCD, independent of QT prolongation.

Conclusions and future directions: Specific cardiology assessment and interventions may be required for the congenital or unmasked Brugada ECG pattern in schizophrenia. The current long-term standard of care for BrS is an implantable cardioverter defibrillator (ICD), but post-implantation psychological effects must be considered. Careful use of antipsychotic and other psychotropic medications is necessary to minimize proarrhythmic effects due to impact on cardiac sodium and calcium ion channels. When prescribing such drugs to patients with schizophrenia, clinicians should be mindful of the potentially fatal unmasking of Brugada ECG patterns and how to manage it. We present recommendations for psychiatrists managing this patient population.

Keywords: Antipsychotics; Brugada ECG pattern; Clozapine; Implantable cardioverter defibrillator; Long QT syndrome; Psychosis; Sudden cardiac death.

Fig. 1

Scoping review search strategy schematic and results yield.

Fig. 2

Pathway of changes in cardiac conductivity in exogenous drug-induced and congenital ion-channel abnormalities. Left panels: Brugada syndrome pathway; leading to ST segment elevation, but no changes in QT interval. Right panels: Long QT syndrome; leading to prolonged QT interval, but no ST segment elevation. Final common outcome is increased risk of sudden cardiac death (SCD).