Prolonged QT Risk Assessment in Antipsychotic Overdose Using the QT Nomogram

Berling, Ingrid; Isbister, Geoffrey K.

doi:10.1016/j.annemergmed.2014.12.005

Cited by 51 publications

(36 citation statements)

References 28 publications

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“…There had been reports of sudden cardiac deaths associated with antipsychotics, particularly thioridazine, for years before sertindole, but this was the first FDA intervention in the matter. In vitro studies have shown the ability of antipsychotics to block the potassium rectifier channel (I Kr ) that is involved in the repolarization of the ventricles (Berling & Isbister, 2015;Fujii et al, 2014, Polcwiartek et al, 2015, Vieweg et al, 2013. However, in vitro studies have shown that despite risperidone's ability to inhibit this channel by 80% at the highest concentrations, it had minimal effect on cardiac conduction (Berling & Isbister, 2015;Vieweg et al, 2013).…”

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confidence: 99%

“…Fujii et al (2014) stated that they found an association between dosing, polypharmacy and QTc prolongation; however no doses were actually published. Another study found mixed results when plotting various antipsychotic doses against QTc, however all of the cases involved overdoses (Berling & Isbister, 2015).…”

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confidence: 99%

“…This is measured via an electrocardiographic (ECG) machine and corrected for heart rate (QTc) as it shortens with increasing heart rates (Glassman & Brigger, 2001 a QTc ≥ 500 milliseconds (ms) or an increase ≥ 60 ms from baseline, in secondary, drug-induced, is considered clinically relevant for increasing the risk of ventricular arrhythmias, including torsade de points (Camm et al, 2012) In 1966 this term was developed to describe a malignant polymorphic ventricular arrhythmia characterized by a twisting pattern of the QRS complex and associated with syncope and sudden death (Glassman & Brigger 2001). Most episodes are transient and self-limited, but 1-20% can lead to sudden death (Berling & Isbister, 2015;Camm et al, 2012;Girardin et al, 2013;Polcwiartek et al, 2015). Since this term was coined in congenital long QT syndrome, it is still unclear if drugs that prolong the QTc interval behave similarly and carry the same risk for inducing torsade de pointes (Glassman & Brigger, 2001).…”

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confidence: 99%

“…Additionally, many studies used antipsychotics at higher doses than used in common practice or even used multiple antipsychotics with cumulative doses higher than those on monotherapy (Berling & Isbister, 2015;Fujii et al, 2014;Glassman & Brigger, 2001). In the majority of studies with haloperidol, for example, the agent was administered intravenously and in an acute care or intensive care patients with intubation-related agitation.…”

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confidence: 99%

“…In vitro studies have shown the ability of antipsychotics to block the potassium rectifier channel (I Kr ) that is involved in the repolarization of the ventricles (Berling & Isbister, 2015;Fujii et al, 2014, Polcwiartek et al, 2015, Vieweg et al, 2013. However, in vitro studies have shown that despite risperidone's ability to inhibit this channel by 80% at the highest concentrations, it had minimal effect on cardiac conduction (Berling & Isbister, 2015;Vieweg et al, 2013). Additionally, a study by Pfizer failed to display any additive QTc prolonging effects of potent CYP inhibitors in the presence of six antipsychotics, which included haloperidol, olanzapine, quetiapine, risperidone, thioridazine and ziprasidone.…”

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confidence: 99%

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The Prevalence and Significance of Antipsychotic Dosing on QTc Prolongation

DeGrote¹,

Shuman²,

Khan³

2017

JPR

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QTc prolongation is a common black box warning within medication labeling. However, it is unclear if QTc prolonging drugs carry the same risk for torsade de pointes as primary or congenital prolongation. The majority of previous studies regarding antipsychotics are limited by a variety of factors. This was a retrospective, cohort study amongst 114 patients at the FHCC to examine the risk of developing QTc prolongation and torsade de pointes in relation to antipsychotic dosing. The primary objective is to determine the incidence rate and mean of QTc prolongation stratified to dose of five antipsychotics. The secondary objective is to determine the incidence of QTc of ≥ 500 msecs and torsades de pointes stratified to dose. The frequency of QTc prolongation was analyzed using chi-square and Fischer's exact test as appropriate with a p < 0.05 being labeled as significant. The average length of QTc prolongation stratified to the dose of antipsychotic was analyzed using linear regression analysis. Dose dependency of QTc prolongation with the five antipsychotic drugs of interest (haloperidol, ziprasidone, olanzapine, risperidone, and ziprasidone) was not supported in this study based on the non-significant linear regression analyses.However, the frequency of torsade de pointes and changes of > 60 msec in the QTc were relatively rare. Thus frequent monitoring is likely unnecessary unless the patient has a prolonged QT at baseline or other risk factors.

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The Prevalence and Significance of Antipsychotic Dosing on QTc Prolongation

DeGrote¹,

Shuman²,

Khan³

2017

JPR

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Schizophrenia and Related Psychoses

2021

The Maudsley Prescribing Guidelines in Psychiatry

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Despite disagreements about nomenclature, patients who develop schizophrenic or schizophrenialike symptoms in later life are often seen in clinical practice. Questions about the etiology of late-life psychotic disorders and about their similarities or differences from early-onset disorders remain unanswered. Neuroimaging techniques have been used to study patients with late onset of psychosis, and in substantial subgroups of patients (from 25% to 100% in various studies) compared with agematched control subjects, structural and functional abnormalities have been found. We review the literature on imaging in late-life schizophrenia and related psychotic disorders, and we present data from our own investigations of patients with these disorders. We discuss the potential usefulness of imaging evaluations in patients with late-onset disorders, and we offer suggestions for future investigations.

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