Antipsychotic Dose Mediates the Association between Polypharmacy and Corrected QT Interval

Abstract

Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = −12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = −2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.

Long‐term antipsychotic polypharmacy prescribing in secondary mental health care and the risk of mortality

“…Furthermore, our findings need to be interpreted within the wider clinical and treatment context. Despite the lack of a consistent significant effect of APP on mortality, when prescribing this regimen it is important to bear in mind that APP continues to be associated with more severe side‐effects . In addition, the notion that more is better, in relation to adding additional antipsychotics and increasing treatment dose, has been consistently rejected by empirical research , indicating that once an optimal dose and response is reached, adding additional treatments makes little difference.…”

First-generation antipsychotics and QTc: any role for mediating variables?

“…No other exclusion criteria were set in terms of specific psychiatric diagnoses. The settings, sampling strategies, and inclusion/ exclusion criteria are fully described elsewhere (Nosè et al, 2015;Barbui et al, 2016).…”

“…Thus, we capitalized on data from a large, crosssectional, national survey, the STAR Network QTc study, based on a representative sample of people recruited from mental health services across Italy (Nosè et al, 2015;Barbui et al, 2016). We assessed the mediating roles of different, relevant, clinical factors possibly involved in the relationship between treatment with FGAs and QTc interval.…”

Ventricular Arrhythmia during Tracheal Intubation and Extubation under General Anesthesia Possibly Induced by Amisulpride: A Case Report

“…Though tracheal intubation and extubation may lead to sympathoadrenal excitement, sustained ventricular arrhythmia is rare, even in patients undergoing cardiac surgery 6). It is well known that, antipsychotics may cause arrhythmia, such as QT interval prolongation, frequent ventricular premature beat and torsades de pointes, even cardiac arrest 7–9). Increasing evidence suggests that psychotropic drugs can increase the risk of sudden cardiac death 10).…”