QT prolongation in mental health patients: contributory factors and clinical significance

Patients with psychiatric disease have increased morbidity and mortality. Psychiatric patients are at increased risk of sudden cardiac death, with antipsychotic medication potentially contributing to this (in one aspect at least) presumably via the development of a prolonged QT interval on the electrocardiogram (ECG) and consequently the potentially fatal arrhythmia torsade de pointes (TdP). In recent decades, some antipsychotic drugs (APDs) have been removed from the market due to their risk of QT prolongation, whilst a number of newer drugs have not passed early drug development phases due to their affinity for cell channels that cause QT prolongation. This creates a problem at the individual patient level, as antipsychotic medication can improve the quality of life for patients who suffer from a mental health illness. Defining the individual drug risk and balancing that against the benefit to the patient is necessary to provide high level patient care. The aims of this PhD are to investigate clinically-useful tools for individual risk assessment of drug-induced QT prolongation in hospital patients; investigate the prevalence of antipsychotic medication use in the Australian population; determine which antipsychotic medications have an accepted, clinically significant, increase in risk of QT prolongation; and investigate what proportion of psychiatric inpatients currently on antipsychotic medication have QT prolongation. A further aim, beyond this thesis, is to investigate the magnitude of association between psychiatric inpatient admission and the use of antipsychotic and antidepressant medications with mortality. In conclusion, the research outlined herein demonstrates an approach to assessing drug-induced QT prolongation; an approach to identifying individual drugs that are associated with QT prolongation; a review of the underlying prevalence of QT prolongation within a population using drugs at risk; and a path forward on how to further increase the body of knowledge on this topic. This knowledge will enable clinicians and patients to make evidenced-based medication choices for populations as well as individuals at risk of TdP.