Can Zoloft cause sudden cardiac death

Study gives the all-clear for SSRIs

NOTTINGHAM.Antidepressants are among the most frequently prescribed drugs worldwide, especially the selective serotonin reuptake inhibitors. The suspicion that serotonin reuptake inhibitors can increase the cardiovascular risk and that arrhythmias, heart attacks or strokes occur more frequently during therapy has been simmering for some time.

In 2011, for example, the FDA recommended that citalopram be dosed up to a maximum of 40 mg per day in order to avoid the QT prolongation that a study found with higher doses. The European Medicine Agency made a similar statement. However, the data situation is not uniform and there are hardly any studies on younger patients.

Carol Coupland from the University of Nottingham and her colleagues have now searched for a possible connection, especially in younger people (BMJ 2016; 352: i1350).

In a total of 238,963 patients between the ages of 20 and 64 who were diagnosed with depression between January 2000 and July 2011, they tracked how many had a myocardial infarction or an insult or a transient ischemic attack (TIA ) and how many had to be treated for cardiac arrhythmias.

They considered the various antidepressant groups separately and differentiated according to dose and duration of therapy. The patient data came from the QResearch database. A database of over 600 general practitioners from across the UK that lists the health records of more than twelve million patients.

Risk changes over time

During the study period, the doctors treated had issued 3,337,336 prescriptions for antidepressants. SSRIs were prescribed most frequently with a share of 71.3 percent, followed by tricyclic and structurally related antidepressants (16.0 percent) and "other antidepressant substances" (12.7 percent).

The monoamine oxidase inhibitors accounted for a negligibly small proportion (0.05 percent) with only 1791 prescriptions. During the study period, 772 patients had suffered a myocardial infarction, 1106 a stroke or TIA and 1,452 patients had to be treated for cardiac arrhythmias.

Looking at the entire study period, the doctors could not find any significant connection between the various classes of active ingredients and the cardiovascular diseases examined. There were, however, drug-specific differences based on different periods of time: The risk of myocardial infarction was almost half lower in the first year of taking SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, sertraline) compared to not taking any medication (HR 0.58, 95%). -KI 0.42-0.79). With the tricyclic lofepramine, however, the risk of myocardial infarction was three times higher in the first year of treatment (adj. HR 3.07; 95% CI 1.50-6.26).

A stroke risk twice as high was found in the group of "other active ingredients" in the first 28 days of intake (adj. HR 2.72; 95% CI 1.45-5.08). The insult / TIA rate was also increased 85 to 182 days after discontinuation of "tricyclic and related antidepressants" (adj. HR 1.82; 95% CI 1.21-2.74).

Cardioprotective Effect of SSRIs?

When taking tricyclic and structurally related antidepressants, the risk of arrhythmia in the first 28 days after the start of treatment was almost twice as high (adj HR 1.99; 95% CI 1.27-3.13) than without the drug. With the SSRI fluoxetine, however, the risk of developing cardiac arrhythmias within the study period was significantly reduced (adj. HR 0.74, 95% CI 0.59-0.92). No significant increase in risk was found with citalopram, not even with doses above 40 mg per day (adj. HR 1.11; 95% CI 0.72-1.71).

Coupland and her colleagues rate the most important result of the study as the fact that SSRIs apparently do not increase the risk of heart attack, stroke or arrhythmia in younger patients.

Rather, there were indications that taking SSRIs reduces the risk of heart attacks and arrhythmias, especially with fluoxetine. The extent to which the SSRI actually has a cardioprotective effect must first be examined in detail, according to the study authors.

In contrast to earlier surveys, citalopram has not shown an increased risk of cardiac arrhythmias, emphasize the doctors, but at the same time admit the wide confidence interval and the low number of patients.

Citalopram should therefore only be prescribed if the indication is strict. Coupland and her colleagues also rate the significantly higher cardiovascular risk with lofepramine as particularly important compared to all other antidepressant substances.