Patients who were prescribed selective serotonin reuptake inhibitors (SSRIs) to treat depression did not have an increased risk of arrhythmia, MI, stroke or transient ischemic attack, according to an observational, cohort study from a large primary care database.

Lead researcher Carol Coupland, PhD, of the University of Nottingham in the U.K., and colleagues published their results online in The BMJ on March 22.

The researchers noted that previous research has found depression increases the risk of cardiovascular outcomes. However, they added that it is unclear if the use of SSRIs and other antidepressants increase or reduce the risk of cardiovascular outcomes. They also mentioned that the use of antidepressants in the U.S. increased by more than 400 percent from 1988-94 to 2005-08 and have become the third most commonly used prescription drug.

For this study, the researchers selected 238,963 patients from the QResearch version 34 primary care database, which included longitudinal health records on more than 12 million patients from more than 600 general practices in the U.K. All patients had their first depression diagnosis between the ages of 20 and 64 from Jan. 1, 2000, and July 31, 2011.

Patients were excluded if they had a previous depression diagnosis, if they were diagnosed with schizophrenia, bipolar disorder or another type of psychosis or if they had received prescriptions for lithium or antimanic drugs. Patients were also excluded if they had received a prescription for an antidepressant before the study entry date or more than 36 months before they were diagnosed with depression.

The mean age of patients was 39.5 years old, and 61 percent of patients were women. They were recruited from 687 practices.

After a median follow-up period of 5.2 years, 87.7 percent of patients received a total of more than 3 million antidepressant prescriptions. Of the prescriptions, 71.3 percent were for SSRIs, 16 percent were for tricyclic and related antidepressants and 12.7 percent were for other antidepressants. The median duration of treatment was 221 days.

The researchers said citalopram was the most commonly prescribed antidepressant (31.5 percent), followed by fluoxetine (23.9 percent) and amitriptyline (7.3 percent).

During the first five years of follow-up, there were 1,452 new arrhythmia diagnoses for an incidence rate of 16.2 per 10,000 person years, including 20.1 per 10,000 in men and 13.8 per 10,000 in women. There were also 772 new diagnoses of MI for an incidence rate of 8.6 per 10,000 person years, including 16.2 per 10,000 in men and 3.9 per 10,000 in women. In addition, there were 1,106 new diagnoses of stroke or transient ischemic attack for an incidence rate of 12.3 per 10,000 person years, including 17.3 per 10,000 in men and 9.3 per 10,000 in women.

The researchers mentioned there were no significant associations with arrhythmia, MI, stroke or transient ischemic attack for any of the antidepressant classes during the five-year follow up period.

They added that there was some evidence SSRIs were associated with a reduced risk of arrhythmia and MI. Fluoxetine was associated with the lowest risk of arrhythmia and MI, although there were no significant difference between the SSRIs.

Further, the researchers said that the risk of arrhythmia was significantly increased in the first four weeks after patients began taking tricyclic and related antidepressants, while lofepramine (a tricyclic drug) was associated with a significantly increased risk of MI during the first year of follow-up.

The researchers also mentioned that the FDA and European Medicines Agency issued warnings in 2011 regarding taking high doses of citalopram, which may be associated with a risk of arrhythmia. Although there was no increased risk of arrhythmia in patients taking citalopram in this study, the researchers said that only a small number of patients were treated with high doses of the drug.

“We suggest that high doses of citalopram should not be prescribed without a strong indication, particularly in patients with any risk factors for an increased QT interval,” the researchers wrote.