Antidepressants not associated with increased risk of cardiovascular conditions

Commonly used antidepressants, known as selective serotonin reuptake inhibitors (SSRI), are not associated with an increased risk of cardiovascular conditions, such as heart attacks and strokes in people aged below 65, finds a study published in The BMJ.

Depression is known to increase the risk of cardiovascular outcomes, but whether antidepressants, particularly selective serotonin reuptake inhibitors, increase or reduce this risk remains controversial.

This is important because antidepressants are one of the most commonly prescribed drugs, and cardiovascular diseases are a leading cause of death and disability worldwide.

In this latest study , a team of UK-based researchers involving the Universities of Southampton and Nottingham, examined associations between different antidepressant treatments, and rates of three cardiovascular outcomes in people with depression.

The study cohort included 238,963 patients aged 20 to 64 with a diagnosis of depression made between 2000 and 2011, identified using the UK QResearch database.

The researchers looked at antidepressant class, including tricyclic and related antidepressants, SSRI, and other types, as well as dosage and duration of use.

Patients were monitored for occurrence of heart attacks, strokes or transient ischaemic attacks, and arrhythmia (an irregular heartbeat), and followed up until 2012.

Factors such as age, sex, smoking status, alcohol consumption, co-morbidities and use of other drugs were accounted for.

Overall, the study found no evidence that SSRI were associated with an increased risk of arrhythmia, heart attacks, or stroke/transient ischaemic attacks in people with depression over the five year period.

But there was a significant doubling of risk of arrhythmia during the first four weeks of taking tricyclic and related antidepressants.

In addition, there was some indication that SSRI were associated with a reduced risk of heart attacks, particularly with the use of fluoxetine.

Absolute risks of heart attacks were six per 10,000 for SSRI over one year, and four per 10,000 for fluoxetine compared with 10 per 10,000 for non-use.

Citalopram, the most commonly prescribed drug among the cohort, was not associated with an increased risk of arrhythmia, even at higher doses. In 2011, the FDA and EMA both issued warnings about taking high doses of the drug following safety concerns.

Michael Moore , Professor of Primary Care Research at the University of Southampton, who led the Southampton team, comments: “The numbers of people taking long term antidepressant treatment has increased relentlessly for the last 15 years and now as many as one in 10 adults are taking these medications. With so many people taking treatment rare side effects may become more important and there have been concerns that long term treatment may be associated with circulatory problems like heart attacks and strokes.

“This large study using routine data failed to find any increased risk associated with SSRI which are the most commonly prescribed drug class. There have been recent drug alerts issued for citalopram in relation to heart rhythm problems but no increased risk was identified by the research. We cannot rule out a very small excess risk as only small numbers of people were taking high doses but these results are certainly reassuring.”

This is an observational study so no firm conclusions can be made between cause and effect. Nevertheless, the study authors say "these findings are reassuring in light of recent safety concerns about selective serotonin reuptake inhibitors."