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.

Elevation of ST After Successful Primary PCI with Acute Myocardial Infarction Patient: Hyperkalemia Induced Brugada Phenocopy

“…The main etiologic categories are myocardial ischemia and pulmonary embolism, metabolic conditions (hyperkalemia), mechanical compression, myocardial and pericardial disease, ECG modulations, and others (electrical injury, etc.). Drugs that block the sodium channels and produce a BrP are not considered BrP, but rather true Brugada patterns unmasked by forcing the channel dysfunction 9 . Therefore, patients with BrP have a negative provocative challenge with a sodium channel blocker, a lack of family history for syncope or sudden death, lack of aborted sudden cardiac death and a negative genetic test for BrS mutations.…”

Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: an in-depth genetic exploration of population samples

“…50 Some people start off with normal ECG readings after which factors such as fever or metabolic disorders 'unmask' a Brugada pattern and schizophrenia may be another such factor. 14 Dysfunction of the autonomic nervous system might play a role herein, as it is involved in schizophrenia and possibly also Brugada syndrome. 26 It is not likely that the effects we found are due to psychotropic medication use, since such medication primarily impacts the QT interval and the effect of schizophrenia on Brugada was not mediated by QT in a multivariable MR analysis.…”

“…11,12 Brugada syndrome, a rare arrhythmia with a population prevalence of 0•05% 13 , is also more common among individuals with schizophrenia. 7,14 It is characterized by ST-segment elevation in ECG recordings and associated with an increased risk of sudden death in young adulthood. 15 While anti-psychotic medication can have cardiac side-effects, its use does not explain these associations.…”

Antipsychotic-Related Fatal Poisoning, England and Wales, 1993–2019

“…This being the case, it remains unclear whether the apparent increase in deaths attributable to a fatal arrhythmia in patients with schizophrenia is due to drug treatment or to the underlying disease 43,44 . That heart conditions, such as Brugada syndrome, may be unmasked by APs is a further consideration 45,46 . In the case of “sudden cardiac deaths” in those younger than 35 years, the role of genetic testing has been cited as an important feature in both establishing an underlying diagnosis and in screening at-risk family relatives 47 .…”