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Newer antidepressants don't appear to carry an increased risk of cardiovascular events, according to findings from a British cohort study.

As a class, selective serotonin reuptake inhibitors (SSRIs) didn't hike the individual risks of arrhythmia, stroke, or MI, , of the University of Nottingham in England, and colleagues .

Interestingly, citalopram -- which has a boxed warning about QT prolongation -- was not associated with arrhythmia, even at high doses. But the researchers acknowledged that the "numbers in this category were relatively small" and that the finding contrasts with studies, including randomized controlled trials, that have found QT interval prolongation in patients on the drug.

Torsades de pointes, the type of arrhythmia most closely related to QT interval prolongation, "is extremely rare, so cohort studies, including ours, cannot rule out an association for this particular type of arrhythmia," Coupland and colleagues wrote.

, of the University of Pennsylvania, who was not involved in the study, said psychiatrists are aware of the relationship between citalopram and QT interval prolongation, although it's a "somewhat separate issue" from arrhythmia in general.

Still, the "prolonged QTc data come from prospective data in a clinical trial, with ECG monitoring, so I have no doubt about their validity," Weintraub told MedPage Today.

And he said that while it's "hard to draw too many conclusions from these large observational studies ... I think our sense is overall that newer antidepressants are safe from a cardiovascular/cerebrovascular standpoint."

, of Columbia University Medical Center and a spokesperson for the American Psychiatric Association, agreed that there “aren’t any shocks here.”

“I think there’s reassurance,” Muskin said. “There’s no logic that they should cause MI or embolic stroke,” noting that SSRIs are mild anticoagulants.

Researchers have known that depression is linked to an increased risk of cardiovascular outcomes, but it's not clear if using antidepressants, particularly SSRIs, increases or decreases that cardiovascular risk.

Only citalopram carries an FDA cardiovascular risk warning, which solely pertains to the prolonged QT interval issue, with a recommendation not to dose more than 40 mg a day.

Coupland and colleagues looked at three cardiovascular outcomes separately -- myocardial infarction, stroke or transient ischemic attack (TIA), and arrhythmia -- among 238,963 patients ages 20 to 64 from a cohort of general practice patients in the U.K., where the mean age was 40 and 61% were women.

Over 5 years' follow-up, 772 patients had an MI, 1,106 had a stroke or TIA, and 1,452 had an arrhythmia.

Overall, the researchers found no associations between antidepressant class and risk of heart attack, although in the first year of treatment, those on SSRIs actually had a significantly lower risk of MI compared with not taking SSRIs (aHR 0.58, 95% CI 0.42 to 0.79).

Among individual drugs, fluoxetine was associated with a significantly reduced MI risk (aHR 0.44, 95% CI 0.27 to 0.72) -- but the tricyclic antidepressant lofepramine carried a significantly higher MI risk (aHR 3.07, 95% CI 1.50-6.26).

There were no associations between antidepressant class or individual drugs and the risk of stroke or TIA.

In general, antidepressant classes were not tied to risk of arrhythmia -- but this risk was increased during the first month of treatment with tricyclic antidepressants (aHR 1.99, 95% CI 1.27-3.13).

Fluoxetine appeared to be protective against arrhythmia (aHR 0.74, 95% CI 0.59 to 0.92), and, interestingly, citalopram was not associated with arrhythmia risk even at high doses.

Weintraub noted that the study "didn't involve older people, who likely have a different risk profile."

Muskin agreed that the paper "would have been better" if patients 65 and up were also evaluated, but this "doesn't take away from the study. You just know that when you extrapolate to the elderly, you have to be more careful."

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