Psychiatric Issues in Heart Disease

James L. Levenson, MD

Professor, Departments of Psychiatry, Medicine, and Surgery; Chair, Division of Consulatioin-Liasion Psychiatry; Vice Chair, Clinical Affairs, Department of Psychiatry, Virginia Commonwealth University School of Medicine in Richmond

Depression and Heart Disease

Major depressive disorder (MDD) is the most common psychiatric disorder in patients with CAD, with a prevalence of approximately 15% to 20% in those with stable or unstable CAD (ie, myocardial infarction and unstable angina). This percentage is much higher than in the general population.³ MDD may be even more common after coronary artery bypass graft surgery, approaching 30% in some studies.⁴ Depression is also very common in congestive heart failure, with a prevalence of up to 20%. Studies using depression symptom (ie, not diagnostic) measures report even higher rates in cardiac patients. Despite such extensive studies of depression in heart disease, the diagnosis is still often missed, and only a minority of depressed patients receive treatment; fewer, yet, receive adequate treatment.

Depression not only commonly occurs alongside CAD, but also negatively affects outcome in CAD. Depression appears to be an independent risk factor for the development of CAD, with the magnitude of risk approximately 1.5–2.0. The magnitude of the effects of depression on morbidity and mortality in CAD is on par with the effects of the recognized medical risk factors. In a large epidemiologic study,⁵ MDD tripled the relative risk of cardiac mortality in those without heart disease and quadrupled it in those who did have cardiac disease. MDD is a significant predictor of mortality after an acute myocardial infarction (MI), with a 3–4-fold increased risk of death, which is equal to the effect of predictors like history of MI or indices of cardiac function.^6,7 In patients with CAD undergoing cardiac catheterization, MDD has been found to be a better predictor of cardiac morbidity and mortality than physiologic measures such as left ventricular function.⁸ Patients hospitalized for unstable angina who also had depressive symptoms were four times more likely to have MI or die the following year than were those without depression (after adjusting for other factors).⁹ In patients who have coronary artery bypass graft surgery, perioperative depression predicts an increased risk of both subsequent cardiac events as well as mortality.

Patients with CAD who are depressed also have poorer health-related quality of life and more functional disability in CAD, and depression has been found to be a stronger determinant of health status than objective measures of heart disease like stenosed coronary arteries, signs of ischemia, and ejection fraction.¹⁰ Depression also adversely affects patients with congestive heart failure, worsening symptoms of heart failure, eroding health-related quality of life and functional capacity, and increasing the risk of death.

A number of explanations have been considered to account for the effects of depression on CAD.^2,3 Depression is closely associated with nicotine addiction, but depression still adversely affects CAD outcome even after controlling for smoking. Depression may interfere with compliance with recommended lifestyle changes, medication, and cardiac rehabilitation. Depressed patients may have alterations in platelet aggregation mediated by alterations in plasma serotonin. Another potential mechanism is reduced heart rate variability in depression, which may explain the increased risk of ventricular arrhythmias and sudden death in depressed cardiac patients. It is also possible that some of the adverse effects of depression are mediated through the cardiac effects of stress, as described below. Pro-inflammatory mediators associated with depression may also be a contributor to CAD.¹¹

Depression and cardiac disease often share some symptoms in common, which can complicate diagnosis. Insomnia and anorexia occur in both, but sadness and anhedonia occur predominantly in depression. In advanced heart failure, severe anorexia, weight loss, fatigue, poor concentration, and diminished libido all occur. In such patients, the diagnosis of depression should usually be reserved for those who also have psychologic symptoms of depression.

Anxiety, Stress, and Heart Disease

Symptoms of anxiety are also frequent in patients with heart disease, particularly during acute coronary events and arrhythmias. A variety of presentations are common, including panic attacks, generalized anxiety, hypochondriacal anxiety, obsessional rumination, and acute and posttraumatic stress reactions. In younger patients, panic attacks and paroxysmal atrial tachycardia may present with very similar symptoms, be difficult to discriminate between, and also commonly overlap in the same patient. In the past, an association between panic disorder and mitral valve prolapse was described, however neither is a sensitive or specific marker for the other. The mitral prolapse that has been associated with panic attacks is usually of no hemodynamic significance, and there do not appear to be any important clinical consequences of the association.

Anxiety also adversely affects outcome in CAD. Anxiety after MI may lead to more frequent episodes of unstable angina and more recurrent MI, after controlling for confounding factors including depression.¹² Post-MI anxiety is one of the strongest predictors of in-hospital complications.¹³

Anxiety’s adverse effects on outcome in CAD may be mediated via effects on heart rate variability, QT interval prolongation, or other abnormalities in autonomic nervous system responses.¹⁴ As with depression, some of anxiety’s effects may be related to the effects of stress on the heart. In studies of CAD patients under controlled laboratory conditions, acute experimental stress has been associated with increases in heart rate and blood pressure, and with silent (ie, asymptomatic) myocardial ischemia.

Most patients who receive automatic implantable cardioverter-defibrillators (AICDs) receive them after experiencing life-threatening ventricular arrhythmias, an anxiogenic stressor in itself. A defibrillator discharge is extremely unpleasant physically, and reminds patients that they are still prone to potentially lethal arrhythmias. It is thus not surprising that in the early days of AICDs there was a high rate of anxiety and other psychiatric disorders in the recipients. However, as the treatment has become more familiar and more widely used, the frequency and severity of anxious reactions has diminished. However, a new potential source of anxiety has been the recent recall of selected AICDs, confronting patients with the difficult choice whether to risk the morbidity associated with replacing the device, versus keeping a defibrillator which has a small chance of being defective.

Type-A Behavior

The relation between type-A behavior and CAD remains controversial. Type A is a complex construct of multiple elements, including impatience, hostility, intense achievement drive, and time urgency. The findings to date have been divided on whether type-A behavior is a risk factor for the development of CAD and a predictor of worse outcome. Overall, there is more support (albeit limited) for type-A behavior as a risk factor for developing CAD, than as a cause of increased morbidity or mortality in those who already have CAD. Of the type-A traits, hostility has been the most consistently associated with increased coronary events and mortality.¹⁵ Anger, which is related to but not identical to the concept of hostility, appears to be an especially potent trigger of ischemia.¹⁶ How hostility or other elements of type-A behavior might lead to CAD, or worsen its outcome, is unknown, but it is speculated to be due to alterations in the balance between sympathetic and parasympathetic nervous system activity.

Cognitive Disorders

Post-operative delirium was extremely common in the early days of open-heart surgery, but the incidence has declined over time in large part due to improvements in surgical technique and cardiopulmonary bypass technology. Delirium also sometimes occurs in the post-operative period following coronary artery bypass graft (CABG) surgery. More subtle cognitive dysfunction is present in approximately 50% of patients after CABG 1 week after surgery, with approximately 25% of the patients still significantly cognitively impaired at 6 months.¹⁷ Persistent cognitive dysfunction in patients with CAD is most often vascular in origin since these patients frequently also have cerebral atherosclerosis. In severe heart failure, with ejection fraction <15%, reduced cognitive performance is due to poorer cerebral perfusion.

Hypertension

Because most hypertension is essential (ie, idiopathic hypertension), psychologic factors have been intensively studied as potential contributors to its pathogenesis. The influence of psychologic factors in the development of hypertension is less clear than in CAD despite many studies of the potential role of personality, coping style, and blood pressure reactivity in hypertension. In some (but not all) studies, a high level of anxiety has been a strong prospective predictor for the development of hypertension, as has job strain. One prospective study of psychosocial risk factors for hypertension found that two of the components of type-A behavior (time urgency/impatience and hostility) were each associated with double the risk of hypertension at follow-up, but symptoms of anxiety and depression were not predictive.¹⁸ However, another prospective epidemiologic study found that combined symptoms of depression and anxiety were associated with an increase for hypertension.¹⁹ Studies of psychologic treatments for hypertension, primarily relaxation techniques and biofeedback, have sometimes found modest but clinically significant sustained reductions in blood pressure. However, drug therapy is much more effective than such techniques.

Psychiatric Side Effects of Cardiac Drugs

Neuropsychiatric side effects are common with many cardiovascular drugs. Almost all can cause dizziness. Among the antiarrhythmics, lidocaine is the most likely to cause agitation and psychosis. Central nervous system side effects are common with some of the older antihypertensive drugs like reserpine, methyldopa, and clonidine. Common psychiatric side effects of selected cardiovascular drugs are shown in the Table.

Psychiatric Drugs in Patients with Heart Disease

Selective serotonin reuptake inhibitors have almost no reported adverse cardiac effects, but have caused sinus bradycardia on rare occasions. Sertraline has been studied in the most depth in the The Sertraline Antidepressant Heart Attack Randomized Trial, which found no significant adverse effects in patients who had active coronary artery disease.²⁰ Bupropion, mirtazapine, venlafaxine, and duloxetine have occasionally been associated with relatively small increases in blood pressure, but appear to be safe for use in patients with cardiac disease. Tricyclic antidepressants (TCAs) can cause orthostatic hypotension and conduction delay (QRS or QT prolongation). An overdose of TCAs may cause fatal ventricular arrhythmias. TCAs have type-1A antiarrhythmic effects and therefore are considered relatively contraindicated after MI.

Hypotension caused by psychiatric drugs is usually mediated via a-adrenergic blockade. It is common with low potency typical antipsychotics, very common with clozapine, and less common with other atypical antipsychotics. Clozapine is unique among antipsychotics in causing myocarditis, usually presenting as a dilated cardiomyopathy, with an estimated rate between 1/500 and 1/10,000. Approximately 85% of the cases occur during the first 2 months of treatment with clozapine.

Antipsychotics all appear capable of prolonging the QT interval, but this has primarily been of clinical significance with low-potency phenothiazines, pimozide, and droperidol (droperidol and mesoridazine have been withdrawn in the United States). In patients with other causes of QT interval prolongation (especially familial long QT syndrome) or the concurrent use of other QT prolonging drugs, there is some increased risk of the ventricular arrhythmia, torsade de pointes. An electrocardiogram should be obtained for patients who have a history of heart disease, hypokalemia, hypomagnesemia, or a personal or family history of sudden death or syncope.

There has been recent concern regarding an increased risk of death in elderly demented patients who have received antipsychotics, with some of the deaths being cardiovascular. Rather than this absolutely contraindicating the use of antipsychotics in such patients, it is prudent to carefully balance the risks and benefits of treating versus not treating psychotic symptoms in demented patients.

Benzodiazepines have no recognized cardiac adverse effects (except in severe withdrawal) and have been safely used in coronary care units for several decades. Buspirone is also free of cardiovascular effects.

Although lithium can cause sinus node dysfunction, it has been safely used even in patients with severe heart disease. Lithium levels are difficult to regulate in patients with congestive heart failure who are on salt-restricted diets and receiving varying dosage of diuretics, and it is usually best avoided in such patients. Valproic acid and lamotrigine have no significant cardiovascular effects. Carbamazepine has a similar side-effect profile to the tricyclics.

Cholinesterase inhibitors may have vagotonic effects on the heart (eg, bradycardia). While a number of clinical authorities have reported the safe use of modest doses of stimulants in patients with significant cardiac disease, including congestive heart failure, coronary artery disease, arrhythmias, and hypertension, recent concern has been raised regarding cardiac risk. Here, too, a careful weighing of potential risks versus benefits is warranted rather than total avoidance.

Electroconvulsive Therapy

Current acute coronary artery disease (MI, unstable angina) or recent serious ventricular arrhythmias are relatively strong contraindications to ECT. However, ECT has been used safely in a variety of heart diseases, including in patients with CAD, congestive heart failure, pacemakers, and implanted defibrillators, as well as after aneurysm repair and even heart transplant. Rasmussen and colleagues²¹ provide a more detailed review on this subject.

Disclosure: Dr. Levenson is on the depression advisory board for Eli Lilly.

References

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