Depression and heart disease: What do we know, and where are we headed?
ABSTRACTDepression and heart disease have an intricate association and perhaps a causal relationship. We review the current status of depression and heart disease and provide an algorithm for diagnosing and treating depression in cardiac patients that internists and cardiologists can use in their daily patient encounters.
KEY POINTS
- Depression is a risk factor for new cardiac disease and has a detrimental impact in established cardiac disease.
- Numerous mechanistic pathways have been implicated.
- In clinical trials, drug therapy and psychotherapy have not clearly decreased the rate of cardiac death in depressed cardiac patients, but they did improve depression, adherence to drug therapy, and quality of life.
- Clinicians should routinely screen for depression in cardiac patients and should not hesitate to treat it.
- Eligible patients should routinely be referred to cardiac rehabilitation programs.
SSRIs seem to be better than other antidepressants for cardiac patients
Before SSRIs were available, tricyclic antidepressants were the mainstays. Subsequent analysis showed the tricyclics to have an unfavorable risk-benefit profile in cardiac patients,101 and since other types of antidepressants are available, tricyclics should be avoided altogether in cardiac patients.102
Whether the SSRIs actually decrease one’s risk of death in heart disease is still an issue of debate, but there are encouraging signs. In SADHART, the rate of death and recurrent nonfatal MI was 20% lower in the patients randomized to receive sertraline, although the difference was not statistically significant.82 In ENRICHD, patients who did not respond to cognitive behavioral treatment or had severe depression could receive sertraline or other antidepressant drugs on a nonrandomized basis, and those who did had a 42% lower incidence of death or recurrent MI.103
The SADHART and CREATE trials provide convincing evidence of the cardiac safety and antidepressant efficacy of two SSRIs (sertraline and citalopram) in depressed cardiac patients. Mirtazapine, studied in MIND-IT, was not effective in treating depression in cardiac patients, although it had a better adverse effect and safety profile than tricyclic antidepressants. 104
Clinical observations indicate that SSRIs are associated with less risk of MI than non-SSRI drugs.105,106 During hospitalization for acute coronary syndromes, patients on SSRIs had lower rates of recurrent ischemia and heart failure but higher bleeding rates than patients not taking SSRIs.107 In a retrospective study of patients undergoing coronary artery bypass grafting, those on an SSRI before surgery had higher rates of death and rehospitalization.108 Being on antidepressant medication could be interpreted as a surrogate marker of having more severe depression before surgery; this issue clearly requires further study.
Given current observations and recent data from interventional trials coupled with the safe drug-interaction profile of sertraline and citalopram, these two SSRIs are recommended for treating depression in cardiac patients. If the patient is also receiving an anticoagulant, one should monitor for bleeding, as all SSRIs are associated with a prolonged bleeding time. Monitoring for rare cases of hyponatremia and bradycardia should also be part of early follow-up.
Do cardiac drugs have psychiatric effects?
Some concerns have arisen about cardiovascular drugs causing or aggravating psychiatric conditions.
Statins were once suspected of causing clinical depression or even suicide. However, subsequent studies have not substantiated this.109,110 In fact, long-term statin use has been associated with improved psychological wellbeing. 111 Whether the favorable psychological profile is due to an improved lifestyle, a direct noncholesterol effect, or an immunomodulatory effect has yet to be determined.
Beta-blockers have been suspected of increasing depression and fatigue. Robust metaanalyses have shown no increased risk of depressive symptoms but a small increased risk of fatigue and sexual dysfunction.112 Observational trials in the first year post-MI have shown no differences between beta-blocker users and nonusers in depressive symptoms or depressive disorders.113
Statins and beta-blockers offer both immense cardiac benefit and low risk, and both may be prescribed with confidence in depressed cardiac patients.
Refer patients for cardiac rehabilitation
The American Association of Cardiovascular and Pulmonary Rehabilitation strongly recommends screening cardiac patients for depression and referring them to cardiac rehabilitation programs.114 Typical programs run 12 weeks, affording an opportunity to further listen to and assess the patient and to promote general wellness via nutrition, stress management, and exercise.
These interventions by themselves can favorably affect depression. Blumenthal and colleagues,115 in the Standard Medical Intervention and Long-Term Exercise (SMILE) study, found that exercise was as effective as drug treatment in reducing depression. In addition, stress management as a psychosocial treatment in cardiac rehabilitation can reduce death rates in cardiac patients.116
Unfortunately, many patients who are eligible for cardiac rehabilitation programs do not avail themselves of them.117
Our algorithm
FUTURE DIRECTIONS FOR RESEARCH
Can we predict the course of depression?
We need to identify better which patients will have a spontaneous remission of their depressive symptoms after a cardiac event, which patients will linger with depression, and which patients will best respond to treatment. Risk stratification, using the psychiatric history, symptoms and severity of depression, and genetic predisposition118 might allow improved targeted therapies.
Does depression cause cardiac disease?
The link between depression and heart disease can be seen as merely an association. In the interventional trials performed to date, we have not yet seen a reduction in cardiac deaths when depression was treated, challenging any assumption of a causal relationship between depression and heart disease. The debate about association vs cause is germane to behavioral medicine,119 and the better we understand the mechanistic pathways, the better we can advise patients and treat depression comorbid with heart disease.
Behavioral medicine is currently measuring the aspects of depression associated with cardiac disease, including the spectrum of somatic (body) and affective (mood) symptoms120 and specific areas such as sympathetic arousal and early morning insomnia.121 If we can determine the depression subtype that carries a worse cardiac prognosis, we may untangle the biobehavioral links that bidirectionally bridge clinical depression and cardiac disease.
Another area of interest, emotional vitality (a positive state associated with interest, enthusiasm, excitement, and energy for living) has been shown to protect against coronary heart disease122 and holds much promise.
In the plenary lecture of the Academy of Psychosomatic Medicine in 2006, Frasure-Smith spoke of the “pleiotropism” of our antidepressant interventions on the various risk factors in depressed cardiac patients.123 We need behavioral medicine studies that elucidate these mechanisms, guiding more precise treatments as well as novel therapies. Omega-3 fatty acids, which benefit heart disease and clinical depression,124 will be used in a randomized controlled trial by Lespérance and colleagues.125 We await the results of this exciting research.
