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Identifying and managing depression in patients with coronary artery disease

Pragle, Aimee Salzer, MMSc, MSPH, PA-C; Salahshor, Susan, PhD, PA-C, DFAAPA

Journal of the American Academy of PAs: May 2018 - Volume 31 - Issue 5 - p 12–18
doi: 10.1097/01.JAA.0000532111.83132.8b
CME: Primary Care

ABSTRACT Coronary artery disease (CAD) is the leading cause of death among adults in the United States. Despite advances in cardiac care, patients who have CAD and a diagnosis of depression have higher rates of morbidity and mortality. This article examines the epidemiology, clinical presentation, screening tools, and treatment recommendations for these patients.

Aimee Salzer Pragle is an assistant professor in the PA program at Florida State University in Tallahassee, Fla. Susan Salahshor is an assistant professor in the PA program at Florida State University and lead PA in abdominal transplant at the Mayo Clinic Florida in Jacksonville. The authors have disclosed no potential conflicts of interest, financial or otherwise.

Acknowledgment: The authors would like to thank James Zedaker, MPAS, PA-C, DFAAPA, and Mark Archambault, DHSc, PA-C, for assistance with this manuscript.

Earn Category I CME Credit by reading both CME articles in this issue, reviewing the post-test, then taking the online test at Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of May 2018.



Box 1

Box 1

When a patient presents for treatment of coronary artery disease (CAD), clinicians face a number of key questions. Was the patient recently diagnosed with CAD? Has the patient recently experienced a myocardial infarction (MI) or is the patient at risk for one? These illustrate the types of questions necessary to design an optimal care plan. Finding adequate time to also discuss the patient's feelings about managing CAD can be challenging. However, the clinical visit is a valuable opportunity for clinicians to talk with their patients who have CAD about their risk of depression and how to treat it. Heart disease remains the leading cause of death and disability in US adults.1 Between 20% and 40% of patients with CAD suffer from clinically significant depression.2

Depression in patients following a cardiac event, such as an MI, can continue for months or years after the event.3 CAD and depression are diseases that significantly reduce patient quality of life and place a substantial economic burden on society.4 Patients who experience an acute cardiac event and have untreated depression are more likely to have an impaired quality of life, increased risk of mortality, are less likely to participate in cardiac rehabilitation, and are at increased risk of new cardiovascular events.5 Although effective treatments are available, studies have confirmed that the symptoms of depression are not always identified in patients with CAD.6 Huffman and colleagues found that depression is significantly underdiagnosed and undertreated in busy inpatient cardiac units.7 Clinicians must understand the diagnostic tools to screen for depression and how to use them when treating patients with CAD. Managing patients with CAD is challenging. Clinicians who understand the diagnosis and treatment for CAD complications such as depression can provide effective and efficient care with pharmacologic and nonpharmacologic interventions.

Box 2

Box 2

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In a 1993 study, Frasure-Smith and colleagues sought to determine if the diagnosis of major depression in patients with CAD who were hospitalized following MI would affect cardiac mortality over the first 6 months after discharge.8 The study showed that depression was a significant predictor of mortality.8 This landmark study emphasized the need for clinicians to focus on screening for depression in cardiac patients. May and colleagues analyzed data from 24,137 patients who were diagnosed with CAD by angiography between 1993 and 2016.9 Fifteen percent (3,646) of these patients were diagnosed with depression. Results of this study showed that a depression diagnosis at any time following a CAD diagnosis was found to more strongly predict death than risk factors, comorbidity, severity of CAD, and follow-up events.9

Screening for depression in patients with CAD also can help to identify those at higher risk of suicide, homicide, and substance use disorders. Depression is the most common psychiatric disorder in patients who die by suicide.10 A study evaluating 19,857 patients with CAD who died by suicide found that those with a history of psychiatric illness were 64 times more likely to commit suicide following an MI.11 Further studies show that patients who self-harm and are at risk for suicide also have an increased risk for violent crimes including homicide.12 Clinicians can help identify and provide appropriate triage and treatment for at-risk patients. Research has shown that monitoring and active treatment in patients at high risk for suicide may reduce rates of suicide.13

Depression can also increase the risk of substance use disorders.14 Thirty percent to 42.8% of patients with major depression have substance use disorders during their lifetime.15 For patients with depression and CAD, using alcohol or illicit drugs can exacerbate depression symptoms and increase the risk for serious cardiac complications. Excessive alcohol intake may lead to cardiomyopathy and an increased risk of hypertension.16 Smoking and consuming excess alcohol produces synergistic effects that increase the risk of MI.17 Patients who use illicit drugs such as amphetamines have significantly increased risk for an acute MI.18

Astute clinicians recognize that patients with CAD may already have depression or are at risk for depression. Established risk factors for depression in patients with CAD include younger age, female sex, history of depression, social isolation, previous cardiac event, and diabetes.19 This is demonstrated in several studies, including a meta-analysis that compared sex differences of major depression in patients with CAD. Results showed that major depression is two times greater in women than men with CAD.20 In addition, a study by Mallik and colleagues found that women age 60 years or younger had significantly higher rates of depression at the time of hospitalization for MI than older women and men.21

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The experience of suffering from CAD and possible acute cardiac events can be traumatic for patients. In addition, clinicians may find multiple challenges in correctly identifying underlying depression. During a clinical visit or hospitalization, the focus may be more on asking the patient questions about cardiac health, new medications they are required to take, participating in cardiac rehabilitation programs, and trying to make healthful lifestyle modifications. This can be overwhelming and create an environment in which the patient and clinician are less likely to recognize the importance of subtle symptoms that could indicate depression. Over time, as patients develop coping strategies and an understanding of their diagnosis, these stress symptoms may naturally diminish. But as discussed earlier, 20% to 40% of patients with CAD will suffer from clinically significant depression.2

Having an understanding of the signs of depression and asking the patient pertinent health history questions are vital. Symptoms that can be a manifestation of depression and the criteria for diagnosis of major depression are described in Table 1.22,23



Symptoms of depression in patients with CAD may be difficult to recognize because they are also symptoms of cardiac disease. For instance, fatigue and insomnia are frequently seen in patients after hospitalization for a cardiac condition and do not always indicate depression.24 Both clinicians and patients may not recognize these symptoms as indicating a need to evaluate further. Because of this, depression frequently is undiagnosed and untreated in patients with CAD. A review of data collected through the multicenter cohort TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients Health) study showed that only 30% of patients with CAD and major depression are diagnosed with depression.25

By understanding the prevalence of depression in patients with CAD, clinicians can create an environment in which patients are encouraged to discuss symptoms that could indicate depression. Understanding the application of depression screening tools in this setting provides a tool for communication with patients regarding depression and CAD. Patients may be unable to work if they have a physically exerting occupation, or may not have the resilience to complete activities such as caring for children and completing household tasks. By discussing these important topics with patients, the clinician can begin to understand the challenges the patient is facing and if depression is an underlying issue.

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Three of the most-used tools for assessing patients for depression are the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HAM-D), and the Patient Health Questionnaire (PHQ-9).26 The Cross Cutting Level I of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is a comprehensive assessment tool that is becoming more commonly used. The Columbia Suicide Assessment Screen is the national and international standard screen most widely used for suicide. Another useful resource is Zero Suicide, an online training link that provides a toolkit for understanding strategies for suicide prevention in healthcare systems.27 Because depression has many comorbidities that contribute to adverse outcomes in patients with CAD, using assessment tools to identify risk factors is an essential component in diagnosing depression in patients with CAD.

Each assessment tool has benefits and limitations depending on the clinical or hospital setting. A major benefit of the PHQ-9 tool is that question 9 has good reliability for suicidal ideation. Also, in the clinical setting the PHQ-9 can be implemented in a brief amount of time.28 In comparison, the BDI can be used in the clinic; however, it is more extensive in length versus the PHQ-9. Due to this situation, the BDI may be better served in a clinical research environment rather than in a primary care setting.29

Historically, the HAM-D has been considered the gold standard for evaluating depression in a clinical setting. However, there has been some discussion that due to focus on insomnia versus other areas it may have limitations in serving as a definitive tool for evaluation of depression.30 Similar to the BDI, the HAM-D takes more time to administer compared with the PHQ-9.

The Cross Cutting Level I of DSM-5 has many benefits for evaluating depression in patients with CAD. This tool includes screening for suicide and substance abuse.31 As discussed earlier, patients with depression and CAD are at an increased risk for these conditions, so identifying them is critical for providing care.

Clinicians seeking to evaluate for depression in patients with CAD can choose the assessment tool that best meets the clinical setting and addresses each patient's presentation. Depression assessment tools provide a framework for the treatment-to-target strategy. With this strategy, the same assessment instrument is used at each visit to check the patient's progress. This helps clinicians determine if the treatment plan is working or if adjustments are needed.32Table 2 describes each assessment tool, benefits, and limitations in application.



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Various studies have shown that screening for depression may not consistently improve morbidity and mortality for patients with CAD.33 However, a recent evaluation of data from the TRIUMPH study showed that patients with CAD who have had an acute MI have a 70% to 90% increased risk of death at 1 year post-MI if they have been diagnosed with depression but not treated.25 Identifying these patients and providing appropriate management can help to reduce morbidity and mortality.

The most effective nonpharmacologic management for moderate to major depression in patients with CAD is cognitive behavioral therapy (CBT).34 This therapy encourages focus on five key areas—environment, thoughts, emotions, behavior, and psychology. Patients are encouraged to develop skills to help them change stressful areas that are within their control.

Depression is a known risk factor for treatment nonadherence.35 For patients with CAD and who are also recovering from a cardiac event, depression has been shown to decrease participation in exercise programs.36 Two cornerstone cardiology recommendations after an MI are enrollment in a cardiac rehabilitation program and compliance with aspirin therapy for secondary prevention. Studies show that depression decreases patient adherence to these recommendations. Identifying the appropriate treatment for patients with depression and CAD can make a tremendous difference in the course of cardiac recovery and improving adherence to medical recommendations.

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Consider antidepressant medication in patients with:

  • severe depression
  • chronic or recurrent depression
  • depression with psychotic features
  • depression with a positive response to previous medication use
  • positive family history of depression
  • inability to participate in psychotherapy.

The antidepressant medications used to treat depression can lead to cardiac adverse reactions.37Table 3 shows the cardiac adverse reaction profile of the pharmacologic agent discussed.



Citalopram, sertraline, fluoxetine, and mirtazapine are commonly prescribed antidepressants for patients with CAD.38,39 Tricyclic antidepressants are contraindicated because they cause adverse cardiac reactions (Table 3). Management of depression decreases depressive symptoms and readmission rates for patients with CAD. The rate of readmission for post-MI patients with depression versus patients without depression was about 33% and 16%, respectively.40

Sertraline and citalopram are selective serotonin reuptake inhibitors (SSRIs) used as first-line therapy for major depression in patients with CAD. Sertraline doses from 50 to 200 mg daily were used to treat patients with CAD. Sertraline was found to be safe and effective with no significant change in the primary cardiovascular outcome of left ventricular ejection fraction.41

Citalopram was compared with placebo in the CREATE trial. Citalopram and CBT taken daily for 12 weeks was more effective for moderate to severe depression post-MI than CBT only. Citalopram was started at 10 mg daily for 7 days and increased to 20 mg daily. In the CREATE trial, citalopram was effective by 6 weeks.42 CBT and interpersonal psychotherapy (IPT) individually were not as effective without citalopram.41 Citalopram causes bradycardia, so patients should monitor and record BP and pulse and notify their provider if their heart rate is 60 or below. The FDA warns that citalopram should not be prescribed at doses greater than 40 mg/day because of the risk of cardiac electrical abnormalities at high doses. Avoid prescribing the drug in patients with conditions such as congenital long QT syndrome; these patients are at greater risk for torsades de pointes, ventricular tachycardia, and sudden death if they take drugs that can prolong the QT interval. If citalopram must be used in patients with conditions with a risk of QT prolongation, closely monitor patients' ECGs and electrolyte levels.43

Mirtazapine, an atypical antidepressant, is effective in post-MI depression. The MIND-IT trial was a randomized controlled trial that compared mirtazapine with placebo for 24 weeks.44 Patients were given 7.5 mg to 45 mg of mirtazapine daily over the first 8 weeks for acute management and then continued for 16 weeks. No statistically significant difference was found in the adverse reactions or readmissions in the mirtazapine or the placebo group. Mirtazapine can be used safely to manage mild or major depression in patients with CAD.

Fluoxetine is indicated for the management of mild to major depression 90 days post-MI in patients with depression who have a tendency toward hostility. Fluoxetine is an SSRI and is recommended after citalopram and sertraline have been tried.45 One trial used fluoxetine for 25 weeks with a starting dose of 20 mg daily for 3 weeks followed by an increase to 40 mg at day 21. The most common adverse reactions were chest pain and gastrointestinal symptoms in the fluoxetine and placebo groups. The QRS duration was decreased in fluoxetine group, reducing the risk of dysrhythmias.39

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The US Preventive Services Taskforce (USPSTF) recommends depression screening for all adults and treatment of depression with medication and psychotherapy.46 In the treatment of mental health diseases and disorders, psychotherapy is more effective when combined with antidepressants. Psychotherapy includes: CBT, IPT, problem-solving depression care, and supportive stress management (Figure 1).47 Psychologists and clinically trained social workers provide psychotherapy.41 The Enhancing Recovery in Coronary Heart Disease (ENRICHD) study demonstrated the benefit of concomitant psychotherapy with antidepressants.48



Combining CBT and pharmacologic management can be an effective regimen that is appropriate for depression that is severe, chronic, or does not improve with only pharmacologic therapy. CBT and supportive stress management can be done individually or in group. CBT can be done one to three times per week, for up to 20 weeks, based on the patient's needs. Medicare, Medicaid, and private insurance have increased the coverage for mental illness in the nation due to several factors, including the Affordable Care Act, the Medicare Improvement Act, and pressure from health policy makers and mental health advocates.49,50 Care also is shifting to outpatient management (75%) over inpatient hospitalization (25%).49 In some studies, CBT was used in combination with follow-up telephone calls or Internet-based CBT with no difference in resolution of depression symptoms.51,52

Patients with cardiac disease, cardiac events, and psychiatric diagnosis have responded well to supportive stress management. Like CBT, supportive stress management is weekly and includes follow-up phone calls. Stress management teaches coping skills through scenarios and observation. The psychologist, clinically trained social worker, or mental health professional then gives the patient guided steps on how to relax during stressful times.51

The ENRICHD trial also used problem-solving strategies to prepare patients for difficult moments and thoughts after MI. The problem-solving counseling sessions were individualized for each patient and improved social skills, self-esteem, and satisfaction after 6 months. The counseling groups also involved group sessions to allow sharing of low perceived social support while empowering patients to develop other relationships that were beneficial for their recovery from MI.

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Clinicians in multidisciplinary patient care settings play a vital role in the evaluation, diagnosis, and treatment of depression in patients with CAD. Symptoms of depression can be challenging to detect in the clinical setting, so the first step to caring for these patients should be to develop an understanding of how to use depression screening tools. Once depression is diagnosed in a patient with CAD, the next steps are identifying and implementing appropriate interventions.

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cardiology; coronary artery disease; behavioral health; depression; screening; premature death

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