Heart Rate-Corrected QT Interval Dynamics Following Antidepressant Switching from Escitalopram to High-Dose Venlafaxine: Cardiac Safety Insights from the Early Medication Change Cohort

Electrocardiographic changes indicating a significantly increased risk of adverse cardiac effects, such as heart-rate corrected QT interval prolongation, are rare during antidepressant treatment; however, systematic analyses are lacking. Therefore, our study aimed at investigating the relationship between heart-rate corrected QT interval changes and both dosage and serum levels of escitalopram and venlafaxine in a well-characterized study sample.Two hundred seven depressed patients received escitalopram (10-20 mg/d) for 4 weeks. Non-responders were switched to high-dose venlafaxine (150-375 mg/d) for an additional 4 weeks of treatment. Serum concentrations were measured weekly and electrocardiograms were recorded at baseline, day 28 and day 56. Risk factors for heart-rate corrected QT interval prolongation were included as covariates in the analysis.Escitalopram did not significantly affect heart-rate corrected QT intervals. Switching to high-dose venlafaxine resulted in a significant increase of mean QT intervals from day 29 to day 56 (<i>p</i>=0.007), more pronounced in men (interaction <i>p</i>=0.038). Heart-rate corrected QT interval prolongation occurred in 5% of patients after escitalopram and 12% after venlafaxine; notably, 12 patients experienced critical prolongations, all with higher rates of known risk factors. No correlation between serum concentrations and heart-rate corrected QT intervals were observed.Our findings indicate that escitalopram does not affect heart-rate corrected QT intervals, whereas venlafaxine is associated with a modest but significant heart-rate corrected QT interval prolongation, particularly in males. Although infrequent, critical prolongations highlight the need for individualized risk assessment, especially in patients with risk factors. The lack of correlation with serum concentrations suggests that pharmacokinetic monitoring alone may not reliably predict cardiac risk. Our results underscore the importance of electrocardiogram monitoring with attention to sex-specific and clinical risk profiles.