In 2011, the FDA issued an alert recommending not to prescribe citalopram high doses, due to QT prolongation risk. We explored the clinical background of QT interval prolongation related to serotonin selective reuptake inhibitors (SSRI) use and the clinical implications of safety issues.

A review was conducted to clarify the mechanisms associated with the occurrence of TdP when using SSRI and investigating therapeutic measures to avoid/minimize these effects. The literature search was conducted in PubMed data reviewing articles between 2001 and 2016.

(1) Related to risk factors/intraclass differences: risk factors are increase in QTc interval ≥60ms from the pretreatment value, advanced age, female sex, acute myocardial infarction and electrolytic abnormalities among others. Citalopram appears more likely than others to induce this phenomenon but its importance is under current debate. (2) Related to dose: drug-induced QTc interval prolongation and TdP was associated to citalopram in doses>40mg/day. However, psychotropic drug-induced sudden cardiac death may be an outlier in the absence of identified risk factors for QTc interval prolongation and TdP. (3) Related to poly-pharmacy/management: there is an additive effect when using SSRI and antipsychotics (EKG control is recommended in those cases). Cross-sectional studies showed that SSRI use was not associated with QT interval prolongation. This could be explained by the EKG intra-intersubject variability.

There is little evidence that drug-associated QTc interval prolongation by itself is sufficient to predict TdP. Future research needs to improve its precision to better understand the factors that facilitate/attenuate that progression. Clarifying this may lead to a safer SSRI use.