Acquired QTc prolongation is mostly drug induced. The common mechanism is formation of early after depolarization and prolonged repolarization by blockade of ion channels in cardiac cells. The after depolarization can trigger an arrhythmia and increase risk for torsades de pointes (TdP) , a form of polymorphic ventricular tachycardia occurring in the setting of a prolonged QTc interval. The term, meaning “twisting of the points,” refers to the pattern of the polymorphic ventricular tachycardia seen on the EKG.

QTc prolongation is related to the risk of cardiac mortality, presumably by causing TdP . However, the extent of medication-induced QTc prolongation does not always correlate with level of TdP risk.

Most QTc prolongation is acquired. Medications and electrolyte abnormalities are the most common causes. Medical conditions that increase risk of electrolyte imbalance, predispose to other arrhythmias, or interfere in metabolism of QTc prolonging medications increase risk of QTc prolongation.

See table for risk factors and conditions associated with QTc prolongation. A complete list of medications that can prolong QTc can be found at www.​crediblemeds.​org.

Psychotropic medications prolong QTc by binding to cardiac potassium channels. The QTc prolongation increases the risk of cardiac arrhythmia and sudden death but the absolute risk with these agents remains small. The QTc prolongation can occur at any dose but the risk increases with dose.

Among antipsychotics, ziprasidone causes a greater QT prolongation than many other agents but the absolute increase is modest. It increases QTc >60 ms in <1% of patients and it is rare to see QTc >500 ms (0.06%) [1]. Very few case reports have described TdP with ziprasidone and sudden death has been associated with ziprasidone in less than ten cases [2]. The overall risk of sudden death with ziprasidone is no higher than with comparator medications [3]. Though QTc prolongation is generally dose dependent, the effect with ziprasidone does not seem to depend on dose.

Low-potency antipsychotics are thought to have a higher risk of prolonging QTc, though haloperidol is an exception. Haloperidol prolongs QTc to a lesser extent than ziprasidone but is associated with a higher risk of TdP. Intravenous haloperidol carries a higher risk of TdP than oral or intramuscular administration.

There is some information on newer antipsychotics [4]. Iloperidone may cause QTc prolongation comparable to ziprasidone [5]. Paliperidone causes some QTc prolongation [6] while lurasidone does not appear to cause QTc prolongation.

Among antidepressants, citalopram is the only agent to which the Food and Drug Administration (FDA) attached a warning label [7]. The FDA recommends against doses >40 mg. There is only a modest increase in QTc at 60 mg but the additional clinical benefit is not considered significant enough to warrant an additional risk. There are also case reports of TdP with citalopram. It is unclear whether the overall mortality from citalopram is higher at >40 mg/day but the FDA warning label will remain until further evidence becomes available. Escitalopram increases QTc to a much lesser extent and the FDA has placed no restrictions on its use. No other serotonin reuptake inhibitors have a clinically significant effect on QTc. Tricyclic antidepressants prolong QTc mainly by widening the QRS interval.