In post menopausal women, treatment with antidepressant drugs is associated with an increased mortality risk but not an increase in CDH risk; absolute increase in mortality risk is small, and is similar with SSRI and tricyclic antidepressives (TCA).

Antidepressant drug prescribing is common and has increased considerably since the early 1990’s. This analysis of data from the Women’s Health Initiative (WHI) aimed to determine whether treatment with these drugs affected cardiovascular morbidity and overall mortality in older women. WHI investigated risk factors for chronic illness in generally healthy community-dwelling women in the US, in three RCT and an observational study. For this analysis, participants were women who were not taking an antidepressant drug at baseline and who had at least one follow-up visit. Overall mortality and cardiovascular morbidity were compared over the course of follow-up in those who started any antidepressant drug and those who did not. Outcome events were the first occurrence of coronary heart disease (CHD), defined as fatal plus nonfatal myocardial infarction (MI) or death due to definite or possible CHD; fatal or nonfatal stroke; and all-cause mortality.

There were 161,808 women enrolled in WHI, and of these, 84% (n = 136,293) were eligible for the analysis. At the next follow-up visit, 5,496 (4%) were taking an antidepressant: 55.3% an SSRI alone, 27.1% a TCA only, and 17.6% on mixed or multiple drugs. Mean follow-up for the combined cohort was 5.86 years from the first follow-up visit (max. 10.8 years); mean for the RCT cohort was 7.14 and for those in the observational study 4.80. In total, there were 6,262 deaths, 2,357 strokes, and 2,983 CHD events during follow-up.

Women newly started on an antidepressant drug after the baseline visit had an increased risk of overall mortality compared to those not taking one of these drugs: annualised risk of death per 1,000 women years was 7.79 for those not taking any antidepressant, 12.77 for those taking SSRI (hazard ratio [HR],1.32; 95% CI, 1.10 to 1.59), and 14.14 (HR,1.67; 95% CI, 1.33 to 2.09) for those taking TCA. The difference between SSRI and TCA was not statistically significant after adjustment: CHD HR 1.17 (95% CI, 0.75 to 1.81), stroke HR 1.20 (95% CI, 0.76 to 1.87), and death HR 1.03 (95% CI, 0.79 to 1.33).

SSRI use was associated with an increased risk of stroke (HR,1.45; 95% CI, 1.08 to 1.97), particularly haemorrhagic stroke (HR, 2.12; 95% CI, 1.10 to 4.07). Antidepressant drug use was not associated with risk of CHD.

The authors conclude that in generally healthy postmenopausal women, use of antidepressant drugs may be associated with increased risk of mortality, however use is not associated with any increase in risk of CHD. SSRI may be associated with increased risk of haemorrhagic stroke and fatal stroke. They caution that the absolute increases in risk are small, and while they attempted to adjust for potential confounding factors the possibility of confounding still exists. They note also that untreated depression is itself associated with significant morbidity and mortality. As a result, their findings should be weighed against the benefits of treating depression.

An accompanying Comment discusses the study and its possible implications.