Some but not all antidepressants associated with QT prolongation

ACP Internist Weekly

Citalopram and some other antidepressants were associated with prolongation of the QT interval, a new study found.

The cross-sectional study used electronic health record data on 38,397 adult patients treated between 1990 and 2011 in one Massachusetts health system. All of the patients had a prescription for an antidepressant or methadone (which was included to demonstrate assay sensitivity because of its known effect on QT interval) and had an electrocardiogram (EKG) recorded between 14 and 90 days of the prescription. Studied antidepressants included citalopram, escitalopram, fluoxetine, paroxetine, sertraline, amitriptyline, bupropion, duloxetine, mirtazapine, nortriptyline and venlafaxine.

Results were published by BMJ on Jan. 29.

Researchers found a dose-response association with QT prolongation for citalopram (adjusted beta, 0.10; P<0.01), escitalopram (adjusted beta, 0.58;P<0.001) and amitriptyline (adjusted beta, 0.11; P<0.001), but not for the other antidepressants. Bupropion was associated with QT shortening (adjusted beta, 0.02; P<0.05). More than 400 study subjects had an EKG before and after a dose increase; 59 patients whose citalopram dose was increased from 10 mg to 20 mg had a significant increase in QT (mean increase, 7.8 ms; adjusted P<0.05), as did 107 patients whose dose went from 20 mg to 40 mg (mean increase, 10.3 ms; adjusted P<0.01). Thirteen patients whose bupropion dose increased from 100 mg to 200 mg had a significant decrease in QT (mean decrease, 19.2 ms; adjusted P<0.05).

The study confirmed an association between citalopram and QT prolongation that had been previously identified by other research and FDA warnings, the study authors concluded. Modest prolongation was also found with amitriptyline and escitalopram, but not the other drugs, suggesting that there might some variation in risk within the treatment class. The authors cautioned, however, that the effect sizes were small and that their study population was older and sicker than the average outpatient cohort, since physicians are more likely to order EKGs for such patients.

The study can't answer the question of whether patients on antidepressants should routinely receive EKGs, the authors said, but it may suggest that bupropion treatment would be a reasonable alternative to increasing a patient's dose of citalopram. They called for randomized trials to confirm these apparent associations.