Having a heart attack is depressing. After a myocardial infarction (MI), about 65% of patients have some depressive symptoms, and 20% develop full-blown depression (Guck TP et al., AM Fam Physician 2001;64:(4):641-648). While this may not be a big surprise, it also turns out that the relationship is reciprocal: systematic reviews have found that depression increases the risk of future development of heart disease by 64% (Wulsin et al., Psychsom Med 2003;65: 201-210).
But what do these facts mean in the terms of treatment? Should we treat depressed patients with heart disease the same way we would treat any patient with depression? Should we put patients who have had an MI on prophylactic antidepressants?
The issue of depression and heart disease has become an oddly controversial one over the last year or so. The controversy began innocuously enough, when the American Heart Association officially recommended that all patients with cardiovascular disease (CVD) be routinely screened for depression by their cardiologists or primary care doctors (Lichtman JH et al., Circulation 2008;118(17):1768-1775). Note that this recommendation was not only to screen patients who have had an MI, but any patient with documented cardiovascular disease. This statement was endorsed by our own American Psychiatric Association (APA).
But soon after this recommendation was released, JAMA published a systematic review of the literature in an effort to find out if there is any actual evidence that such screening leads to better outcomes, either in terms of cardiac disease or depression (Thombs et al., JAMA 2008;300:2161-2171). The authors could not find a single study that was designed to answer this question. They did, however, find a few studies showing that depression screening in cardiac populations can, in fact, detect patients with depression (with median sensitivity of 84% and median specificity of 79%). They also located six clinical trials of antidepressant treatment in cardiac patients. It turns out that antidepressant treatment works in this population, but there was no solid evidence that it improved their cardiac disease or their overall survival. They concluded that screening was not helpful.
In a letter of response, a group of psychiatrists pointed out that even if antidepressants don’t improve cardiac outcomes, they do improve depression, which is a debilitating disease in its own right. So why not screen all CVD patients for depression, just in case? (Carney et al., JAMA 2009;301(13):1337). In reply, the authors pointed out that not only did treating such patients not improve cardiovascular outcomes, but the effect on depressive symptoms was extremely modest, accounting for a 1% to 4% change in symptoms compared with those treated with placebo (Thombs et al., JAMA 2009;301(13): 1337-1338, and November 2008 interview in PsychCentral.com, http://tinyurl. com/lboepq).
So who’s right in this debate? It is likely that both sides have merit. For the time being, the official recommendation to screen for depression still stands, so be prepared for an influx of referrals from cardiologists near you.
How Does Depression Increase the Risk of Heart Disease?
Beyond the issue of whether depression screening improves cardiac or psychiatric outcomes, the question of how, or whether, depression contributes to heart disease is an interesting one. While there are no definitive studies answering this question, theories abound. Miscellaneous findings have suggested that depression may cause increases in cortisol and norepinephrine (potentially leading to increased plaque formation); increased production of free radicals (damaging the endothelium); increased fatty acids (causing hyperlipidemia); and decreased parasympathetic tone (causing hypertension and arrhythmias). (For a review, see Wulsin et al., Current Psych 2004;3:20–34).
However, there is no definitive evidence that depression directly causes heart disease through these physiological processes. It may be that depression’s pathogenic effect is indirect because depression leads people to engage in behaviors that put them at increased risk for heart disease. Such behaviors include smoking, drinking excessive alcohol, eating poorly, not sleeping well, not exercising, and not being compliant with their cardiac medications. As psychiatrists, we can use this list with our depressed patient to support their cardiac health.
How Does Having an MI Increase the Risk of Depression?
About 65% of post-MI patients develop some depressive symptoms—but why? On a physiological level, MI may cause lower brain perfusion which may cause depression through some unspecified neurobiological mechanism. Perhaps more importantly, heart disease often forces patients to alter their activities, leading to reduced work hours and consequent financial stress, while limiting pleasurable activities, such as exercise and sex. Furthermore, for many of our patients, a heart attack is their first confrontation with their mortality, and how can this not be depressing?
Antidepressant Treatment in Cardiac Patients
Are all antidepressants equally safe and effective for depressed patients with heart disease? Several large clinical trials have been conducted to answer this question, most of which have acronyms to etch them into your memory.
The SADHART study (Sertraline Antidepressant Heart Attack Randomized Trial) enrolled 369 patients with ACS (“acute coronary syndrome,” a term referring to a heart attack or acute cardiac chest pain) from 40 outpatient cardiology and psychiatry clinics in the US, Europe, Canada, and Australia. It was the first randomized double-blinded placebo-controlled study of antidepres¬sants in this population (Glassman et al., JAMA 2002;288:701-9). The study was funded by Pfizer. Zoloft (mean dose: 70 mg/day) did significantly improve depression and quality of life, but only for those patients whose depression was a recurrence of a prior depressive episode. Patients undergoing their first ever depressive episode after their heart attack did not benefit.
The ENRICHD trial (Enhancing Recovery In Coronary Heart Disease), funded primarily by the National Institute of Health, randomized 2481 ACS patients with depression or “low perceived social support” to either cognitive behavioral therapy (CBT) or routine medical care. Of note, there was no randomization to SSRI treatment, but some patients in both groups received antidepressants (if depression remained after five weeks of CBT, or as part of routine medical care). CBT improved both social isolation and depression, but it did not affect recurrence of MI or death, possibly due to confounding use of antidepressants in both groups. Interestingly, in a reanalysis, they found that SSRI use, was associated with a significant decrease in the risk of recurrent MI and of death (adjusted HR, 0.57; 95% CI, 0.38–0.85) (Beckman et al., JAMA 2003;289:3106-3116).
MIND-IT (Myocardial Infarction and Depression – Intervention Trial), partially funded by Organon (the manufacturer of Remeron/mirtazapine), randomized 91 ACS patients with major or minor depression to either Remeron or placebo. Remeron (30mg/day) was effective in the treatment of post-MI depression, but the effect on cardiac events and mortality was inconclusive (Honig et al., Psychosom Med 2007;69:606-613).
Overall, treatment of depressed cardiac patients with antidepressant medications or CBT is effective for the depression, but only medication treatment may have an effect on cardiac outcome.
Safety of Antidepressants in Cardiac Patients
While SSRIs are associated with increased bleeding times, their use in post-stroke and cardiac patients appears to be safe. Specifically, studies have shown that there is no increased risk of hemorrhagic stroke with SSRI treatment (Kahoka et al., Stroke 2007;38:3049-51), nor is there an increased risk of complications with coronary artery bypass grafting (Kim et al., Am J Cardiol 2009;103: 1391-5).
Many clinicians refrain from giving tricyclics for the first six months after an MI, believing it to be contraindicated because of the possibility of arrhythmias. While there are not many studies, there was a comparison of paroxetine (20mg-30mg/day) to nortriptyline (serum level 50-150ng/mL) in treating depressed patients with ischemic heart disease. Both medications treated the depression effectively, but nortriptyline seemed to cause cardiac problems, while paroxetine appeared safe. Nortriptyline caused a sustained 11% increase in heart rates and 14% reduced heart-rate variability, while Paxil caused no change. More significantly, nortriptyline was associated with seven adverse cardiac events out of 40 treated, or 18%, while Paxil was associated with only one of 41, or 2% (Roose et al., JAMA 1998;279:287-91).
TCPR’s Recommendations: Depressed patients are at greater risk for cardiac problems, and according to some, but not all studies, depressed patients who already have cardiac problems may have better cardiac outcomes if treated with antidepressant medication. Patients who present following an MI are at particular risk for depression, and should be carefully evaluated. CBT, if appropriate, can be helpful for their depression; but, if depression symptoms remain after five weeks of CBT, then it should be augmented by an antidepressant, which may also improve their cardiac outcome. Tricyclic antidepressants should be avoided in patients with a known cardiac history.