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Subscribe to Clinical Compass™ VOLUME 3, ISSUE 5 - FEBRUARY 26, 2008
Treating Depression and Getting to the Heart of the Matter

by Mary Ann Stephens, PhD

The reciprocal link between coronary heart disease (CHD) and depression has been well documented: people with a history of depression are more likely to experience a cardiac event, such as myocardial infarction (MI), and people who have experienced a cardiac event commonly develop depression. The elevated risk of another cardiac event in patients with depression extends beyond five years. Not only are people with depression more likely to have subsequent cardiac problems, they are more likely to have a fatal recurrent cardiac event rather than a nonfatal event. Dr. Alexander Glassman of the Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute has stated that “patients with depression after myocardial infarction, especially those with prior episodes [of depression], should be carefully watched and aggressively treated, because they are at an elevated cardiac risk and less likely to get better spontaneously.”

Evidence-based guidelines for the management of patients with MI and depression suggest the combination of cognitive behavioral therapy and selective serotonin reuptake inhibitors (SSRIs) to be useful.(1) SADHART(2) and CREATE(3) are two large multisite trials that have demonstrated the safety and efficacy of sertraline and citalopram for treating depression in patients with acute MI. Recent findings from the Myocardial Infarction and Depression–Intervention Trial (MIND-IT)(4) have now demonstrated the safety and efficacy of mirtazapine adding to the list of first-line options for patients with post-MI depression.

The January 29, 2008 neuroscienceCME Clinical Compass highlighted the association between depression and CHD in recognition of February as Heart Health Month. We asked our subscribers to let us know how many patients they see who are depressed with comorbid CHD. Fifty-one percent reported that, of their patients who were depressed, about half or more also have CHD; the remainder saw very few patients with depression and CHD, or weren’t sure. The vast majority of respondents (75%) typically treat these patients with both psychotherapy and antidepressants, with the remaining respondents typically treating with psychotherapy/counseling only (5%), antidepressants only (9%), or another form of treatment (7.5%). The alignment of our respondents’ practice with management guidelines for patients with MI and depression is robust and encouraging.

Does treating depression have any impact on subsequent heart health or recurrent cardiac events? In terms of acute recovery from MI, SADHART data showed that sertraline inhibited platelet endothelial markers more than placebo in depressed patients; this effect reduces the chance of forming dangerous blood clots that can lead to a new heart attack.(5) Another promising effect of SSRIs is on heart rate variability (HRV). Post-MI depressed patients tend to have persistently low HRV (relative to non-depressed post-MI patients), which has been linked to death following heart attack. Sertraline(6) and fluoxetine(7) increased heart rate variability, thus improving the chances of recovery from a heart attack. The mechanisms in which SSRIs affect these biologic factors, and the association of these factors with depression, are unknown and subject to further investigation.

Whether treatment of depression improves cardiac prognosis remains unclear. Observational studies have produced mixed results, while pharmacologic(4) and behavioral(8) treatment studies of depression found modest improvements of depression itself, but no impact on recurrent cardiac events. A recent report, however, is shedding some light on this issue.(9) Data derived from MIND-IT(4,10) were examined to determine whether responders to antidepressants at 24 weeks (mirtazapine and/or citalopram) would experience fewer recurrent cardiovascular events. The comparison groups were nonresponders to antidepressants and untreated control subjects. At 18 months post-MI, responders experienced significantly fewer cardiac events than non-responders (event rates were 7.4% versus 25.6%, respectively). More surprisingly, nonresponders were almost three times more likely to have another cardiovascular event relative to untreated control subjects.(9) Of further note, only 9.5% of responders were depressed at 18 months, whereas 58.8% of nonresponders were depressed. These nonresponders represent a particularly challenging and high-risk subgroup. Lead author Dr. Peter de Jonge, in the psychiatry department at the University Medical Center Groningen, the Netherlands, states, “This finding suggests that it is persistent depression that is the key variable and that resistance to acute treatment may be a marker for that. Our findings thus stress the importance of early response to post-MI antidepressant treatment and the need to develop more effective treatments for depression in the context of an MI.” Essential components for effective management of depression in the context of MI must also include frequent monitoring, and dose changes, switching, and/or augmentation of medications, for nonresponse.

It is critical for clinicians who treat people with CHD and/or depression to raise awareness of the co-occurrence of these conditions, and to implement proper diagnosis and treatment procedures. Not only are people with depression less likely to adhere to cardiac medication and exercise regimens, depression compromises overall health status and quality of life. For the latest evidence-based strategies for the assessment and management of depression, logon to neuroscienceCME for "Evaluating and Managing Major Depression: Linking Assessment Measures and Outcomes in Light of the Black Box Warning", "Exploring Atypical Antipsychotics as an Augmentation Option for Major Depressive Disorder", and other CE activities.


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References

  1. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:671-719.
  2. Glassman AH, O'Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-709.
  3. Lesperance F, Frasure-Smith N, Koszycki D, et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA. 2007;297:367-379.
  4. Honig A, Kuyper AM, Schene AH, et al. Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom Med. 2007;69:606-613.
  5. Serebruany VL, Glassman AH, Malinin AI, et al. Platelet/endothelial biomarkers in depressed patients treated with the selective serotonin reuptake inhibitor sertraline after acute coronary events: the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy. Circulation. 2003;108:939-944.
  6. Glassman AH, Bigger JT, Gaffney M, Van Zyl LT. Heart rate variability in acute coronary syndrome patients with major depression: influence of sertraline and mood improvement. Arch Gen Psychiatry. 2007;64:1025-1031.
  7. Khaykin Y, Dorian P, Baker B, et al. Autonomic correlates of antidepressant treatment using heart-rate variability analysis. Can J Psychiatry. 1998;43:183-186.
  8. Berkman LF, Blumenthal J, Burg M, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA. 2003;289:3106-3116.
  9. de Jonge P, Honig A, van Melle JP, et al. Nonresponse to treatment for depression following myocardial infarction: association with subsequent cardiac events. Am J Psychiatry. 2007;164:1371-1378.
  10. van Melle JP, de Jonge P, Honig A, et al. Effects of antidepressant treatment following myocardial infarction. Br J Psychiatry. 2007;190:460-466.



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