Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports

Abstract

Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes (TdP) when using this drug within the approved labeling. We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an 'outlier' manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.

Ventricular fibrillation due to overdose of loperamide, the “poor man’s methadone”

“…At therapeutic doses, loperamide has a poor oral bioavailability of only 10–20%; it is metabolized by the cytochrome P450 (3A4 and 2C8) system with biliary excretion, resulting in minimal systemic absorption [4]. Of note, other medications with effects on the 3A4 system have been linked to ventricular arrhythmias, though causation has not been proven [8]. …”

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers

“…In a previous nonclinical study, quetiapine inhibited the human Etherà-go-go-Related Gene (hERG) at clinically relevant, total plasma concentrations (Kongsamut et al, 2002), although the therapeutic dose of quetiapine appears to have a minimal risk for QT prolongation in patients without risk factors (Hasnain et al, 2014a(Hasnain et al, , 2014b. Therefore, physicians should practice caution when prescribing quetiapine to patients with risk factors such as coadministration of a QT-prolonging drug, comorbid disease, medical conditions, and risk for QT prolongation and TdP with overdose (Hasnain et al, 2014a(Hasnain et al, , 2014b. Therefore, on the basis of postmarketing reports the FDA issued a warning in 2011 that quetiapine could induce QT prolongation and TdP (Hasnain et al, 2014a(Hasnain et al, , 2014b.…”

“…Therefore, physicians should practice caution when prescribing quetiapine to patients with risk factors such as coadministration of a QT-prolonging drug, comorbid disease, medical conditions, and risk for QT prolongation and TdP with overdose (Hasnain et al, 2014a(Hasnain et al, , 2014b. Therefore, on the basis of postmarketing reports the FDA issued a warning in 2011 that quetiapine could induce QT prolongation and TdP (Hasnain et al, 2014a(Hasnain et al, , 2014b. However, no thorough QT (TQT) study has been performed to date in humans to confirm the QT prolongation effect of quetiapine.…”

Quetiapine Addiction in an Adolescent

“…As an atypical antipsychotic, quetiapine increases the risk of metabolic syndrome (Simon et al 2009) and carries a dose-dependent QTc prolongation risk (Hasnain et al 2014). Fortunately, F. did not experience QTc prolongation despite ingestion of 1200 mg. Around 30% of patients on quetiapine gain weight in the first 6 months of treatment, but F. did not gain weight with his quetiapine use (Arango et al 2014).…”