Adverse cardiovascular events in antidepressant trials involving high-risk patients: a systematic review of randomized trials.

OBJECTIVE

To examine whether selective serotonin reuptake inhibitor (SSRI) antidepressants were associated with an increased or decreased risk of cardiovascular adverse events (AEs).

METHODS

We conducted a systematic review of randomized controlled trials published between 1967 and May 2005 that treated patients with cardiac disease, diabetes mellitus, stroke, geriatric age, nicotine dependence, alcoholism, HIV infection, and obesity. We defined serious AEs as death due to a cardiovascular cause, heart failure, stroke, transient ischemic attack, and myocardial infarction. Nonserious AEs were defined as palpitations, chest pain, angina, arrhythmia, hypertension, hypotension-syncope, and unspecified cardiovascular or neurologic events. Adverse event rates were calculated in 4 groups: SSRIs, tricyclic antidepressants (TCAs), other active therapies, and placebo.

RESULTS

Stroke and cardiac patients were the highest-risk groups for cardiovascular AEs. We were unable to detect differences in odds between SSRI and placebo for both serious (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.39 to 1.21) and nonserious (OR 1.18; 95% CI, 0.90 to 1.57) cardiovascular AEs. There was a significant decrease in the odds of nonserious cardiovascular AEs (OR 0.46; 95% CI, 0.24 to 0.86, P = 0.02) for patients receiving SSRIs, compared with TCAs. Over one-half of the selected trials did not report the presence or absence of cardiovascular events.

CONCLUSIONS

This systematic review of antidepressant trials in high-risk patients did not determine whether SSRIs are associated with a greater or lesser risk of cardiovascular AEs. Reasons for this conclusion include the rarity of serious AEs, the lack of large trials in these patients, and a lack of adequate reporting of AEs in published trials. Further trials assessing the risk of cardiovascular AEs and better trial reporting are needed.