January 29th, 2013
Popular Antidepressants May Prolong QT Interval
Larry Husten, PHD
In August 2011 the FDA issued a safety communication recommending that the extremely popular antidepressant citalopram (Celexa) not be used at doses greater than 40 mg/day because of a potential increased risk for serious cardiac arrhythmias associated with prolongation of the QT interval. Now a study published in BMJ lends support to this warning and suggests that other antidepressants may also prolong the QT interval.
Victor Castro and colleagues, using a pharmacovigilance approach, analyzed data from more than 38,000 patients in the Partners HealthCare system who received an ECG after receiving an antidepressant or methadone prescription. (Methadone, which is known to prolong the QT interval, was used to verify the sensitivity of the study.)
People who used citalopram, escitalopram (Lexapro), and amitriptyline, in addition to methadone, were significantly more likely to have a prolonged QT interval (QTc). By contrast, bupropion was associated with a significant decrease in QTc. The investigators also reported a dose-response relationship. However, the size of the effects observed were small.
The investigators reported that almost 20% of the patients were found to have an abnormal QT interval, but duly noted that “the clinical significance of this prolongation, including the risk of induction of torsades de pointes, is unknown.” The authors write that the question of whether patients who receive antidepressants should receive routine ECGs “before and/or after treatment starts cannot be addressed directly by this study.”
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There are a couple of aspects of this study that are worth highlighting. (1) Computer calculations of QTc continue to be very flawed. The authors quote the J Electrocardiol 2011 by Tyl et al which showed improvement in the automated algorithm in current ECG machines. However, in that study a difference in QTc measurements between autmated QTc and manual QTc of <30msec was deemed acceptable. (2) Based on the figure in this BMJ paper by Castro et al, it seems that the mean QTc in the citalopram-treated patients increased from ~432ms to ~445ms; in the escitalopram-treated patients from ~428ms to ~442msec and amitriptyline-treated patients from ~432ms to 440ms. This is in contrast with the increase in the methadone-treated patients with QTc changes of ~430ms to ~454ms. However, thankfully the authors do express caution in reporting their findings, commenting that “the clinical significance of this prolongation…is unknown”. Although I do think that this study is both important and well-done and that the authors’ conclusions are appropriately modest, reducing the complexity of this study to a headline of “Some Antidepressants Tied to Irregular Heartbeat” WebMD-Jan 30, 2013 is neither fair nor accurate.