Published: December 2012

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Do All Antidepressants Cause QT Prolongation?

Information on this subject has been updated. Read the most recent information.

Prescriber Update 33(4): 33-35
December 2012

Medsafe and the Medicines Adverse Reactions Committee (MARC) have recently completed a review of the risk of QT prolongation and/or Torsades de pointes (TdP) associated with antidepressants used in New Zealand1. The MARC concluded that QT prolongation/TdP is a risk of treatment with most of the antidepressants approved for use in New Zealand.

QT prolongation is a measure of delayed ventricular repolarisation and is a surrogate marker for the risk of developing the potentially fatal arrhythmia TdP. The definition of QT prolongation depends on the age and gender of the patient. However, a QTc greater than 500ms or an increase of greater than 60ms during treatment is considered to confer a high risk of TdP. QTc is the QT interval corrected for heart rate.

Risk factors for QT prolongation include female gender, increasing age, family history, hypokalaemia and interactions with other medicines (Table 1). Further information on QT prolongation can be found in the Prescriber Update article 'Drug-induced QT prolongation and Torsades de Pointes — the facts'2.

Table 1: Risk factors for drug-induced QT prolongation/TdP2

Unmodifiable risk factors Potentially modifiable risk factors
Female gender (present in 70% of cases) Hypokalaemia or severe hypomagnesaemia
Increasing age (particularly age >60) Absolute or relative bradycardia (including recent conversion from atrial fibrillation)
Genetic predisposition
  • Congenital long QT syndrome
  • Family history of sudden death
  • Previous history of drug induced QT prolongation
Medicine interactions (refer to Medsafe data sheets for further information)
  • Use of >1 QT prolonging medicine
  • Medicines that inhibit the metabolism of another QT prolonging medicine
  • Medicines that cause electrolyte abnormalities or may cause renal or hepatic dysfunction
Structural heart disease/left ventricular dysfunction Starvation, obesity or metabolic disorders (eg, hyperthyroidism, hypothyroidism, diabetes)
Impaired elimination due to renal or hepatic disease High drug concentrations (eg, rapid IV administration, high doses or overdose)


The MARC concluded that the available data supports an association between the use of tricyclic antidepressants, selective serotonin reuptake inhibitors, maprotiline, mianserin, moclobemide, mirtazapine and venlafaxine and the development of QT prolongation. The MARC considered, due to a lack of comparative data, the relative risk of QT prolongation/TdP between antidepressants or different classes of antidepressants is generally unknown.

Further information on the MARC's opinion regarding the individual antidepressants can be found in the MARC meeting minutes published on the Medsafe website www.medsafe.govt.nz/profs/adverse/Minutes151.htm#3.2.1

Prescribers are advised to consider the risk of QT prolongation as part of their assessment of the risk-benefit balance of antidepressants therapy. Particular care should be taken in patients taking other medicines associated with QT prolongation (eg, antipsychotics) and those with risk factors in addition to age and gender. Specialist advice should also be considered.

Key Messages

  • All classes of antidepressants approved for use in New Zealand appear to carry some degree of risk of QT prolongation. • Specialist advice should be sought if QT prolongation is suspected.
  • Patients should be evaluated for risk factors for QT prolongation prior to starting antidepressant treatment.
  • Antidepressants should be used with caution in patients with risk factors in addition to age and gender for QT prolongation. An ECG should be considered at baseline, steady state, at the time of dose increases and if another QT prolonging medicine is added to their treatment regimen.
  • The possibility of drug-induced QT prolongation or TdP should be considered in patients presenting with new onset dizziness, syncope, palpitations or seizures.
  • If QT prolongation or symptomatic arrhythmia occurs, the antidepressant should be stopped unless there are compelling reasons to continue and specialist advice sought.
References
  1. Medsafe. 2012. Minutes of the 151st MARC meeting 13 September 2012. URL: www.medsafe.govt.nz/profs/adverse/Minutes151.htm#3.2.1 (accessed 15 November 2012).
  2. Medsafe. 2010. Drug-induced QT prolongation and Torsades de Pointes — the facts. Prescriber Update 31(4): 27-9. URL: www.medsafe.govt.nz/profs/PUArticles/DrugInducedQTProlongation.htm (accessed 22 November 2012)
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