Menopause Live - IMS Updates

Date of release: 15 February, 2010

Antidepressant use and risk of cardiovascular disease in the WHI study

There remains enormous controversy concerning the treatment of depression in women, particularly the depression that is premenstrual and postnatal and in the menopausal transition which, in the view of many, should be treated with transdermal estrogens. The role of estrogens is, however, less clear in the postmenopausal woman.  


We know that depression is associated with considerable pathology, apart from the risk of suicide, such as more heart attacks, more strokes, more osteoporosis, more hypertension, more obesity, more Alzheimer’s disease and more non-suicide deaths.


In a recent paper, Jordan Smoller and colleagues have focused entirely upon the Women’s Health Initiative (WHI) study [1]. The cohort was based on the three WHI clinical trials and the WHI observational study. 


Professor Smoller examined the postmenopausal women who were not taking antidepressants at baseline (n = 136,293), of whom 4% (n =5496) reported on the use of some antidepressant at one of the next follow-up visits; 55.3% (n = 3040) were taking only selective serotonin reuptake inhibitors (SSRIs), 27.1% (n = 1490) used tricyclics only, and 17.6% (n = 966) another antidepressant or multiple antidepressants. 


The mean follow-up after the first follow-up visit was 5.9 years. Among the analytic cohort, there were 6262 deaths, 2357 strokes, and 2983 coronary heart disease events during follow-up. Those subsequently taking antidepressants were compared with those patients who did not use antidepressants. There was found to be a 45% increase in stroke, but no significant increase in the risk for ischemic stroke. However, a 210% increase in fatal stroke and a 212% increase in hemorrhagic stroke were recorded. The all-cause mortality was increased by 32%. There was no increase in coronary heart disease with the use of antidepressants and there were no significant differences in risk between SSRIs and tricyclic antidepressants.


This important study seems to have one defect in that we do not have the data for the untreated depressed women, and therefore the increased medical problems and increased mortality may be a result of the depression rather than the therapy. However, depression clearly is a disease associated with much co-morbidity and there is not much evidence that the use of the more fashionable antidepressants influence that. This is an important study which not only emphasizes the risks of depression in postmenopausal women but seriously questions the value of the increasing use of antidepressants. Another contemporary paper by Mojtabai [2] shows a huge increase in the prescription of antidepressants, which has over the last 10 years in the USA increased from 2.2% in 1990 to 10.1% in 2001. The percentage was higher amongst women and older participants. This prevalence represents a more than five-fold increase during this period and was particularly pronounced amongst less severely depressed individuals. Similar trends have been reported in European countries. 
Consistent with prior evidence that SSRIs may increase the risk of abnormal bleeding due to their antiplatelet effects, a significantly increased hazard for hemorrhagic stroke among antidepressants users compared with non-users was observed in the WHI cohorts, although the absolute risks were small. These important findings expose the excess health risks of this therapy and may indicate that the increase in the use of antidepressants may carry additional serious ill effects. Perhaps, it is time for psychiatrists to reconsider the value of transdermal estrogens in hormone-responsive depression in women.


John Studd
Professor of Gynaecology, London, UK


  1. Smoller JW, Allison M, Cochrane BB, et al. Antidepressant use and risk of incident cardiovascular morbidity and mortality among postmenopausal women in the Womens Health Initiative study. Arch Intern Med 2009;169:2128-39. Published December 14, 2009.

  2. Mojtabai R. Increase in antidepressant medication in the US adult population between 1990 and 2003. Psychother Psychosom 2008;77:83-9.