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Steve H. Chin, MD, and Richard Balon, MD

Primary Psychiatry. 2004;11(2):23,28-31

Focus Points

Depression after an acute myocardial infarction is considered an independent risk factor associated with increased cardiac mortality.

Despite the availability of effective treatments, major depression remains underdiagnosed and undertreated.

The case study illustrates the complex interplay of depression and cardiovascular disease following the onset of acute coronary event.

Physicians should be responsive and look for signs of depression in patients with recent myocardial infarction.

Successful treatment of depression can improve prognosis of cardiovascular disease and enhance the overall quality of life.


Depression following a recent acute myocardial infarction is very common and is an independent risk factor associated with increased cardiac mortality. The complex interplay of depression and cardiovascular disease following the onset of acute coronary event can often prevent patients from complying with treatment regimens and disease-modifying behaviors. Furthermore, despite the availability of effective treatments, major depression remains underdiagnosed and undertreated. Thus, appropriate and acceptable treatments need to be built on a foundation of good therapeutic alliance with patients, so that they may feel heard and understood. Physicians should be responsive and look for signs of depression in patients with recent myocardial infarction, as successful treatment of major depression can improve prognosis of cardiovascular disease and enhance the overall quality of life.


In 1999, major depressive disorder (MDD) was the fifth leading cause of disability worldwide. The World Health Organization projects that by 2020, major causes of disability worldwide will be dominated by ischemic heart disease, motor vehicle collision, and MDD.1 Depression is most commonly reported and managed in primary care settings, but unfortunately still remains underdiagnosed and undertreated, even while effective treatments are available. Approximately 50% of people with symptoms of depression do not seek treatment,2 and for those who do seek treatment, 50% are misdiagnosed and mismanaged.3 In the setting of medical illness, depression is often considered to be a common psychological reaction, a response to distress from physical illness, or a result of a decrease in activities of daily living due to medical illness. For this reason, patients’ comorbid depression is often deemed unsuitable for treatment. Moreover, psychological barriers to treatment, such as stigma associated with mental illness and minimization of the need for care, may be important obstacles in the treatment of MDD.

Since the 1930s,4,5 clinicians have reported the association between a diagnosis of depression and higher risk for cardiac mortality. In recent medical literature, there is a growing body of evidence that suggests that depression may cause significant increase in the risk of cardiovascular complications. Adjusted risk of death during the first 6 months after an acute myocardial infarction (AMI) is approximately four times higher in depressed compared to nondepressed patients.6 Furthermore, increased mortality risk is even observed up to 18 months after AMI.7 Depression not only causes poor prognosis, but it is also more frequent among patients with heart disease. Approximately one in six patients with AMI has been identified as experiencing MDD,6,8,9 and the rate of MDD in patients with coronary heart disease is three times higher than in the general population.10 Although the biological mechanism for increased cardiac mortality is not yet clear, depression is clearly associated with poor compliance in risk-modifying behavior. Consequently, depression is considered an independent risk factor for heart disease and is associated with increased mortality after AMI.7 The following case report and discussion will illustrate the complex interplay of depression and cardiovascular disease.

Case Presentation

Mr. A, a 46-year-old man, was admitted to University Hospital in November of 2002 for acute ST segment elevation myocardial infarction (MI). During the hospitalization, the patient underwent primary percutaneous transluminal coronary angioplasty, due to left anterior descending occlusion; the patient was treated by stent placement. He was discharged from the hospital 4 days later without any complications.

Mr. A had previously been in good health, with no prior history of medical or psychiatric diagnosis. His last physical checkup by a physician was at least 10 years prior. For the past 15 years, he had been working in the automotive industry as a division director. The patient was married with two children. He used to be a long-time chain smoker but had decided to stop smoking in November 2002, soon after his MI. He drank small amounts alcohol on occasion (averaging four drinks per month) and denied any history of recreational drug use.

Four weeks after his discharge from the hospital, the patient started to report various physical symptoms. He complained of headache, back pain, abdominal discomfort, nausea, and palpitation. The patient was referred to a neurologist for back pain and headache, and a gastroenterologist for abdominal pain. Subsequently, Mr. A underwent magnetic resonance imaging of his head and spine, and an endoscopy/colonoscopy, all of which were negative. The patient was placed on narcotic analgesics for pain, which resulted in only a minimal improvement.

In March 2003, Mr. A made a decision to visit another gastroenterologist for a second opinion. During the visit, the patient was offered alprazolam and was recommended to see a psychiatrist for an evaluation. From that day on, the patient developed distrust of all physicians and decided to seek out “alternative medicine” to alleviate distress. He turned to acupuncture, herbal treatment, chiropractic and homeopathic medicine; he spent 8 weeks and thousands of dollars without clear benefit. According to his wife, during this period the patient had mood instability, hostility, suspiciousness, and irritability. Mr. A had repeated arguments with his wife, was unable to tolerate his children, and progressed to self-isolation at home. In addition, his symptoms included loss of appetite resulting in a 20-pound unintentional weight loss, decreased interest in sexual activity, and difficulty falling asleep and maintaining sleep (averaging 3 hours of sleep/night). Even with all these symptoms, the patient continued his regular schedule at work and strived to maintain social functioning.

One day in May 2003, the patient tried the alprazolam that he filled in March and noticed mild improvement. Thereafter, he continued his routine follow-up visit with his cardiologist. During a follow-up visit, the cardiologist decided to start the patient on zolpidem for sleep disturbance and chose not to renew the alprazolam.

On June 5, 2003, Mr. A visited University Health Center’s internal medicine clinic, complaining of difficulty sleeping. He reported, “I haven’t been able to sleep for at least 1 week; zolpidem isn’t working any more.” The patient had been taking zolpidem 10 mg tablets without any response. The patient described appropriate sleep hygiene, averaged less than a single cup of coffee in a 24-hour interval, denied reading or working in bed, and denied having a television in his bedroom. During this visit, the patient appeared thin and slightly older than stated age, but groomed and hygienic. He appeared tense with psychomotor agitation. His speech was articulate, logical, and goal directed. Mr. A was cooperative during the interview and maintained good eye contact. He did not display any signs of cognitive deficiency. The patient denied any suicidal ideation, intention, or plan.

During this interview, Mr. A questioned his psychological well being: “I have never felt this way in my entire life; I feel like a different person.” On further questioning, the patient admitted to loss of interest in almost all pleasurable activities, progressive decrease in self-esteem, decreased confidence at work, and difficulty making decisions. The physician thoroughly discussed with the patient and his wife the high incidence of post-MI depression and the potential severe consequences of it. Mr. A agreed to comply with the treatment of depression. He was started on sertraline 50 mg/day and temazepam 30 mg/day. The patient was instructed to return to the clinic within 2 weeks for a follow-up visit.

Mr. A was compliant with his treatment and follow-up visit. In July, on patient request, he was referred to a psychologist for psychotherapy and sertraline was increased. Thereafter, the patient’s somatic symptoms showed gradual improvement and he was able to sleep a full 5 hours at night without disturbance.


Depression is very common immediately after sustaining an AMI. Approximately one third of these patients meet the diagnostic criteria for MDD or minor depression within a few weeks after MI.8 In a study by Frasure-Smith and colleagues,6 16% of patients met diagnostic criteria for MDD during assessments completed 5–15 days after AMI. At the 6-month follow-up point, the mortality rate was 17% for patients with depression, compared with 3% for patients without depression (P<.001). Depression after AMI remains an independent risk factor for higher mortality, even after controlling for the effects of established risk factors of post-AMI morbidity and mortality, including left ventricular ejection fraction, Killip class, age, and history of prior AMI.7

Four weeks after his AMI, Mr. A started reporting a number of somatic symptoms. Due to the fact that his mood symptoms were not appropriately addressed early in his treatment, the patient continued to seek medical subspecialists to deal with his overall distress. When the symptoms of depression remain untreated, patients overuse general medical services, have an higher risk of social and occupational impairment, and experience increased duration of symptoms.11 In a study by Koenig and colleagues,12 41 older inpatients with active MDD were matched with nondepressed controls from the same population. Survival and healthcare utilization were examined during a mean follow-up period of 5 months. In-hospital mortality was significantly higher among the depressed compared with nondepressed controls (6 versus 0 deaths, P=.03). Healthcare utilization in terms of days of inpatient care was significantly higher during the admission (25 versus 14 days, P<.005) and during the follow-up period (16 versus 7 days, P<.05) for depressed patients compared with controls. Hence, medically ill patients with MDD consume more healthcare services and experience higher mortality during their initial hospitalization. After discharge, healthcare service utilization persists among those with depression.

Mr. A responded negatively when the gastroenterologist recommended a psychiatric evaluation. Many people in the general population look at mental illness as a reflection of weakness in character. Even when an individual is in dire need of treatment, the fear that others may be critical and rejecting remains powerful. Especially for Mr. A, a middle-aged man in management position, any sign of weakness might jeopardize his achievements in the industry. Furthermore, perceived social stigma associated with and individual views about mental illness play a significant role in adherence to treatment for depression. In fact, for those diagnosed with mental illness, overcoming stigma is the single largest obstacle to improving quality of life.13 Thus, clinicians’ attention to psychological barriers early in treatment may improve medication compliance and ultimately affect the course of illness.14 It should also be noted that Mr. A’s decision to seek out alternative medicine was a sign of psychosocial distress and decreased quality of life.15

The patient resisted treatment for mood symptoms until the symptoms escalated. Therefore, his treatment was delayed until he was unable to sleep for a full week. Insomnia is a very common presenting symptom among depressed patients immediately following AMI. Those patients with insomnia who do not meet diagnostic criteria for MDD nevertheless have three times as many depressive symptoms (excluding sleep disturbance) as do patients who have not experienced insomnia.16

The patient’s depression did not follow a typical presentation; for example, depressed mood, lack of energy, hopelessness, or helplessness were not reported. Instead, the patient presented repeatedly with somatic symptoms, which camouflaged his condition and left depression unrecognized. Mr. A’s depressive symptoms included irritable mood and hostility; diminished interest in almost all pleasurable activities; sleep disturbance; decreased appetite and unintentional weight loss; psychomotor agitation and restlessness; and decreased self-esteem. These symptoms were persistent for most of the day nearly every day for more than 2 weeks. Thus, the patient fulfilled the diagnostic criteria for MDD with five or more of the nine symptoms (Table).17



Biologic Mechanisms of Depression and Cardiovascular Disease

Depression may directly predispose patients to cardiac events through biological mechanisms such as increased sympathetic activity, autonomic dysregulation, low heart-rate variability, and increased QT variability. Decreased heart-rate variability and increased QT variability is associated with an increased risk of arrhythmia, presumably because there is a greater probability of R-on-T phenomenon and generation of ventricular arrhythmia.18 Post-AMI depression patients have more frequent and longer runs of ventricular tachycardia than do nondepressed patients, a potent risk factor for sudden cardiac death.19 Alternatively, cardiovascular disease and depression may share common etiology, including dysregulation of the serotonin transporter20 or atherosclerosis.21

Studies have hypothesized that elevated levels of serotonin in platelets may be a factor in promoting thrombogenesis in the depressed population.22 Serotonin is normally released by activated platelets, causing enhanced platelet aggregation, which may contribute to the pathogenesis of ischemic heart disease.23-25 In a study by Laghrissi and colleagues,26 higher-circulating platelet factor 4 and β-thromboglobulin, markers of platelet activation, are present in patients who had both depression and ischemic heart disease compared to those without depression.


Tricyclic antidepressants (TCAs) can cause increased heart rate and orthostatic hypotension. TCAs also have significant antiarrhythmic activity because of an electrophysiologic profile similar to that of type 1A antiarrhythmic agents, such as quinidine and moricizine. It is this activity that is responsible for the high rate of mortality after TCA overdose, secondary to ventricular arrhythmias and heart block.27 Given the arrhythmogenic properties, TCAs are currently considered relatively contraindicated in patients with ischemic heart disease.28

Selective serotonin reuptake inhibitors (SSRIs) are associated with fewer cardiovascular side effects, compared with other TCAs.29 The Sertraline Antidepressant Heart Attack Randomized Trial30 investigates the safety and efficacy of sertraline in patients with ischemic heart disease. In this study, sertraline showed no significant effect on left ventricular function, as determined by multiple-gated acquisition scan, systolic or diastolic blood pressure, cardiac conduction intervals, including PR, QRS, QT, or ventricular premature complexes. There was no difference between sertraline compared with placebo on any cardiovascular parameter evaluated. The study also showed that the incidence of severe cardiovascular events was higher in the placebo group (22.4%) compared with the sertraline group (14.5%); however, this difference was not statistically significant (P>.05).

In addition to the favorable safety profile, SSRIs attenuate platelet activation by depleting serotonin storage.31 Serotonin is normally released when platelets are activated by proaggregatory factors, causing increased platelet aggregation.23,24 SSRIs prevent the uptake of serotonin into platelets by inhibiting the only mechanism for platelet storage of serotonin.32-35 The antiplatelet effects of SSRIs have been implicated in an increased risk of gastrointestinal bleeding.36 Van Walraven and colleagues37 described an increased risk of upper gastrointestinal bleeding with increasing serotonin transporter affinity of SSRIs. SSRIs may reduce risk of cardiac mortality through attenuation of serotonin-mediated platelet activation and reduction of other depression-mediated mechanisms. Therefore, the use of SSRIs may confer a protective effect against MI.32,38

In a study of bupropion by Roose and colleagues,39 the cardiovascular effects of bupropion treatment were documented in 36 patients with depression and cardiovascular disease. There was no significant effect observed on heart rate, ejection fraction, or cardiac conduction. Newer antidepressants, particularly venlafaxine and mirtazapine, have not been studied in the depressed patients with ischemic heart disease.

Choice of antidepressant, dosage, and course of treatment need to be individualized; for a first episode of MDD, patients require antidepressant treatment for a minimum of 6 months to prevent relapse, and lifelong antidepressant therapy may be necessary for patients with recurrent illness. The response rate to antidepressant treatment appears to be similar to those reported in patients without comorbid illness. In the treatment of depression, fluoxetine,29 sertraline,30 paroxetine,35 and bupropion39 appear to be reasonably safe in patients with cardiovascular disease. However, patients with heart disease are usually on multiple medications to improve mortality or enhance function. SSRIs, especially fluoxetine, paroxetine, and fluvoxamine, have significant cytochrome P450 isoenzyme inhibitions27; therefore, clinicians need to be familiar with the potential drug-drug interactions.

Additionally, interpersonal or cognitive-behavioral therapy have demonstrated effectiveness as treatments for depression. The Enhancing Recovery in Coronary Heart Disease study,40 a randomized trial of cognitive-behavioral therapy in patients with post-MI depression, has achieved significant improvement in depression and social support. However, the study did not show decrease in cardiac mortality or reinfarction.


Depression develops frequently after the onset of acute coronary event and a growing body of evidence suggests that it is an independent risk factor for cardiac mortality in patients with recent AMI. Depression, which is extremely under-recognized and undertreated, can complicate treatment of coronary events, as it often prevents patients from complying with treatment regimens and health-promoting behaviors. Thus, appropriate treatments should be built on a foundation of good therapeutic alliance between patient and clinician, so that a patient can be diagnosed correctly while also being heard and understood by his or her practitioner. This can only be accomplished if physicians are responsive and look closely for signs of depression in patients with recent MI. Fortunately, successful treatment of MDD can improve prognosis of cardiovascular disease and enhance overall quality of life. PP


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Dr. Chin is resident in the Combined Internal Medicine and Psychiatry Program in the Departments of Internal Medicine and Psychiatry and Behavioral Neurosciences at Wayne State University School of Medicine in Detroit, Michigan.

Dr. Balon is professor of psychiatry in the Department of Psychiatry and Behavioral Neurosciences at Wayne State University School of Medicine.

Disclosure: Dr. Balon is a consultant to Bristol-Myers Squibb, Forrest, GlaxoSmithKline, Merck, and Shire; is on the speaker’s bureau of Bristol-Myers Squibb, Forrest, GlaxoSmithKline, Organon, and Solvay; receives grant and/or research support from Bristol-Myers Squibb, UCB Pharma, Upjohn, and Wyeth; and receives honorarium and/or expenses from Merck.

Please direct all correspondence to: Steve H. Chin, MD, Department of Psychiatry and Behavioral Neurosciences, University Psychiatric Center, 2751 East Jefferson, Ste 200, Detroit, MI 48207; Tel: 313-993-3449; Fax: 313-993-3421; E-mail: