By 2020 depression is predicted to be the second leading cause of disability and mortality in the world, being only surpassed by ischaemic heart disease (Murray and Lopez, 1996).
Major depression is associated with feelings of sadness, hopelessness, helplessness and a lack of interest in normal activities. Patients often complain of symptoms such as a change in appetite, difficulty sleeping, lowered energy, feelings of worthlessness or guilt, difficulty concentrating or thoughts of suicide.
Aside from the diminished ability to function socially or occupationally due to depression, patients are at an increased risk of developing coronary heart disease. This effect is independent of conventional risk factors such as high blood pressure, cigarette smoking or high cholesterol (Glassman et al, 1998). Research also suggests that depression subsequent to a heart attack may increase the risk of death in the next 6 months (Frasure-Smith et al, 1995).
North Western Mental Health, in collaboration with the Department of Cardiology, The Royal Melbourne Hospital were involved in a sponsored trial assessing the safety and efficacy of sertraline (Zoloft ®) in the treatment of major depression following acute coronary syndromes. The study was called the SADHART Study and recruited 369 patients worldwide between April 1997 and April 2001. The results of the study were published in the August 14, 2002 edition of the Journal of American Medical Association (Glassman et al, 2002).
The research compared the safety and efficacy of sertraline (Zoloft ®) and placebo (sugar tablet) for the treatment of major depression in patients who had been hospitalised after a myocardial infarction (heart attack) or unstable angina (heart disease related chest pain).
Sertraline (Zoloft ®) is an antidepressant from the class known as selective serotonin reuptake inhibitors (SSRIs), which act by increasing the levels of the brain chemical serotonin. Older antidpressants such as the tricyclics are contraindicated in patients with heart disease because of associated cardiotoxic side effects. Prior to the SADHART Study there was little available data regarding the use of antidepressants in patients with heart disease as they are generally excluded from clinical trials of treatment for depression.
The SADHART Study demonstrated that sertraline (Zoloft ®) was safe in this patient population, as there were no differences in cardiac function at the end of the 24-week follow up period between patients administered sertraline (Zoloft ®) 50-200mg/day and those who received placebo. Furthermore, the research demonstrated a trend towards fewer severe cardiovascular adverse events (such as another heart attack, stroke or death) for those who took sertraline (Zoloft ®) when compared to the placebo group (14.5% and 22.4% respectively). This equated to a decrease of approximately 20% in serious complications for patients receiving active treatment. Whilst these results are encouraging, the possibility that this trend was the result of chance cannot be ruled out entirely, due to the small number of patients enrolled in the study. We would need a trial of at least 4000 patients to prove that SSRI treatment truly decreased serious complications.
With regard to the effectiveness of sertraline (Zoloft ®), the patients reporting the greatest mood improvement were those with more severe or recurrent depression. For patients with at least one prior episode of depression, 72% responded to active treatment compared to only 51% of those on placebo (p=0.03). Similarly, for patients reporting more severe symptoms of depression, 78% of sertraline (Zoloft ®) patients responded versus 45% of placebo patients (p=0.001). The overall sample also included patients with mild and short-term depression and failed to demonstrate a significant difference between sertraline (Zoloft ®) and placebo. This result may be partially explained however, by the high response rate to placebo for patients with mild or reactive depression. Their symptoms may have resolved spontaneously as a result of the care, attention and support they received from both a cardiologist and psychiatrist as a consequence of their study participation.
In a concluding editorial comment, it was noted that the SADHART Study provided "the first real evidence that at least one of the SSRI antidepressants, sertraline, is safe for use soon after an acute MI or an episode of unstable angina… there is now an alternative to ignoring a comorbid psychiatric disorder that often has devastating consequences for these patients" (Carney et al, 2002). Dr David Barton, a principal researcher from the Royal Melbourne Hospital, also emphasised the positive impact that treatment of depression can have on a patient's quality of life, independent of whether treatment conclusively improves mortality outcomes.
The next step in research is to find out why depression increases the risk of coronary artery disease. If the reason is found, we may be able to intervene in the future to prevent coronary artery disease occurring in the first place.
If you believe that you are suffering from symptoms of major depression, you should consult your local doctor. They will be able to provide an accurate assessment and treatment of your symptoms, or referral to a psychiatrist where appropriate. For further information regarding depression you may also wish to contact Beyond Blue (03 9810 6100 or www.beyondblue.org.au), depressioNet (1300 135 542 or www.depressionet.com.au) or Lifeline (131 114) who provide support for patients and their families.
ReferencesCarney RM, Jaffe AS. (2002). Treatment of depression following myocardial infarction. JAMA; 288(6): 750-751.Frasure-Smith N, Lesperance F, Talajic M. (1995). Depression and 18-month prognosis after myocardial infarction. Circulation; 91: 999-1005.Glassman AH, Shapiro PA. (1998). Depression and the course of coronary artery disease. Am J Psychiatry; 155: 4-11.Glassman AH et al, for the SADHART (Sertraline Anti-Depressant Heart Attack Randomised Trial) Group. (2002). Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA; 288(6): 701-709.Murray CJL, Lopez AD. (1996). The Global Burden of Disease: A comprehensive assessment of mortality and disability, injuries and risk factors in 1990 and projected to 2020. World Bank, Harvard School of Public Health and World Health Organisation, Geneva.