SSRIs Found Not To Increase Risk of Cardiac Events in Depression

Neither a specific antidepressant class nor individual drugs had any influence on the risk of stroke or transient ischemic attack over all of follow-up.

For adults with depression, selective serotonin reuptake inhibitors (SSRIs) did not increase the risk of stroke, transient ischemic attack, or arrhythmia compared with those not taking any antidepressants, according to research published in the BMJ.

No elevated risk of arrhythmia occurred among those taking citalopram either, but those taking lofepramine were 3 times more likely to have a heart attack than those not taking mood medications.

Carol Coupland, PhD, of the University of Nottingham School of Medicine in the United Kingdom and colleagues tracked 238 963 patients, ages 20 to 64, who had been diagnosed with depression between January 2000 and July 2011. The researchers did not include participants taking lithium or antimanic drugs, or who had been diagnosed with schizophrenia, bipolar disorder, or any other psychotic disorders.

Over 5 years of follow-up, 88% of the patients received some kind of antidepressant prescriptions, primarily SSRIs, which comprised 71% of all antidepressant prescriptions. Tricyclics accounted for 16%, and others the remaining 13%. Citalopram, fluoxetine, and amitriptyline were the most commonly prescribed antidepressants. Patients were treated for a median of 221 days.

A total of 772 participants experienced a myocardial infarction, 1106 had a stroke or transient ischemic attack, and 1452 received an arrhythmia diagnosis during the 5 years of follow-up. Neither a specific antidepressant class nor individual drugs had any influence on the risk of stroke or transient ischemic attack over all of follow-up, and antidepressant class had no association with heart attack risk during the full 5 years.

However, compared with patients not taking any antidepressants, patients taking SSRIs had a 42% reduced risk of heart attack in the first year of follow-up. In particular, fluoxetine decreased risk by 56%, while lofepramine tripled the risk. Risk of arrhythmia doubled within the first 28 days of tricyclic treatment and similar antidepressants, but was reduced 26% with fluoxetine over 5 years. Citalopram, even at doses above 40 mg/day, had no association with arrhythmia risk.

“The results of this study are reassuring in light of recent concerns about citalopram and potential risk of arrhythmia,” the authors wrote, although they noted that the small number of patients treated with high doses of citalopram means an increased risk could still potentially exist. “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.”


Coupland C, Hill T, Morriss R, Moore M, Arthur A, Hippisley-Cox J. Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database. BMJ. 2016;352:i1350. doi:10.1136/bmj.i1350.