This cohort study conducted by researchers from the St. Louis Veterans Affairs Medical Center set out to answer the question: Are antidepressants associated with an increased or decreased risk of incident myocardial infarction and all-cause mortality?

93,653 patients aged 25–80 years (average age 51.5 years, 14.1% female, 77.8% White, 57.1% not married) were identified using the US Department of Veterans Affairs database, who had either one inpatient or at least two outpatient codes for depression in their records between 1 October 1999 and 30 September 2000. Patients with at least one primary or secondary diagnosis of heart or cardiovascular disease, or with psychotic or bipolar disorders, were excluded. Patients were excluded from the analyses if a myocardial infarction occurred within 1 month of follow-up; they did not receive a 12-week follow-up from baseline if they only had a diagnosis of dysthymia or psychotic disorders of bipolar disorder.

Receipt of 12 or more weeks of continuous antidepressant therapy was associated with significantly reduced rates of incident MI across classes of antidepressants:

• Selective serotonin reuptake inhibitor (SSRIs) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.44-0.52)
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) (HR 0.35; 95% CI, 0.32-0.40)
• Tricyclic antidepressants (TCAs) (HR 0.39; 95% CI, 0.34-0.44)
• Other antidepressants (HR 0.41; 95% CI, 0.37-0.45)

Risk of all-cause mortality also was decreased with receipt of 12 weeks of pharmacotherapy with all classes of antidepressants (SSRI, SNRI, TCA, Other), with HRs ranging from 0.50 to 0.66.

The researchers concluded:

Across classes of antidepressants, 12 weeks of pharmacotherapy appears to be safe in terms of myocardial infarction risk. Although the mechanism for this association remains uncertain, it is possible that compliance with pharmacotherapy for depression reflects compliance with cardiovascular medications. It also is possible that a direct drug effect or improved depressed mood may attenuate the risk of MI in depressed patients.

Scherrer JF, Garfield LD, Lustman PJ, Hauptman PJ, Chrusciel T, Zeringue A, Carney RM, Freedland KE, Bucholz KK, Owen R, Newcomer JW, True WR. Antidepressant drug compliance: reduced risk of MI and mortality in depressed patients. Am J Med. 2011 Apr;124(4):318-24. [PubMed abstract]