Introduction

Major depression is common among patients

recovering from a myocardial infarction (MI).1-5

Additionally, clinically significant depressive

symptoms are present in other patients whose

symptom severity or duration does not meet

established criteria for a diagnosis of major

depression.5 Over the last decade, increasing

evidence suggests that in addition to its effect on

quality of life, post-MI depression also deserves

attention because of a reported relation to

increased morbidity and mortality.5-8

This evidence report reviews the studies that

have examined depression or depressive

symptoms in patients after an MI and focuses on

the prevalence, clinical significance, treatment,

and methods of evaluating this condition. A

number of studies have evaluated various aspects

of post-MI depression including prevalence,1-4,9-27

its association with mortality, 5-10,20,28-36 and major

adverse events,25,26, 31,37-39 and treatment.10,40-47 This

report addresses the following key questions

regarding post-MI depression.

1. In patients diagnosed with and hospitalized

for acute MI, what is the prevalence of

depression during initial hospitalization for

MI? Depression was defined as symptoms of

depression meeting established threshold

criteria by psychiatric interview or validated

questionnaire.

1a. What is the prevalence of depression

during initial hospitalization for an acute

MI, with and without a history of

previous depression as reported by study

investigators?

2. What percentage of patients with post-MI

depression continue to have depression (or

depressive symptoms) one or more months

after initial hospital discharge?

3. What is the association of post-MI

depression with outcomes independent of

other predictors of post-MI outcomes? PostMI outcomes include:

• Clinical outcomes—total mortality,

cardiac mortality, MI, resuscitated arrest,

stroke, arrhythmias, and

revascularization.

• Quality of life.

• Utilization of health care services—

readmission, total hospital days, and cost

of care. Potential predictors include

demographic and clinical characteristics

of patients that have been reported to be

associated with the risk of post-MI

outcomes.

3a. What is the association of post-MI

depression with surrogate markers of

cardiac risk independent of other

predictors of post-MI outcomes?

Surrogate markers of disease severity

include: heart rate variability, platelet

reactivity, and markers of inflammation

such as C-reactive protein.

Evidence Report/Technology Assessment

Number 123

Post-Myocardial Infarction Depression

Summary

Authors: Bush DE, Ziegelstein RC, Patel UV, Thombs BD, Ford DE, Fauerbach JA, 

McCann UD, Stewart KJ, Tsilidis KK, Patel AL, Feuerstein CJ, Bass EB

Agency for Healthcare Research and Quality

Advancing Excellence in Health Care • www.ahrq.gov

Agency for Healthcare Research and Quality Evidence-Based

Practice
2

4. Do post-MI patients with depression have better

outcomes with depression treatment compared to those

without depression treatment? Depression treatment

includes all interventions intended to have specific impact

on depression, such as antidepressants, cognitive

behavioral therapy, inter-personal therapy, psychosocial

support, and cardiac rehabilitation.

4a. Do outcomes differ with or without improvement in

depression for post-MI patients with depression that

do receive depression treatment?

4b. Do outcomes differ with or without improvement in

depression for post-MI patients with depression that

do not receive depression treatment?

5. What are the performance characteristics (e.g., sensitivity,

specificity, reliability, and predictive value) of instruments

or methods that are used to screen for depression (or

depressive symptoms) following an acute MI?

5a. What are the performance characteristics of

instruments or methods that are used to screen for

depression (or depressive symptoms) following an

acute MI, during hospitalization?

5b. What are the performance characteristics of

instruments or methods that are used to screen for

depression (or depressive symptoms) following an

acute MI, within three months after hospitalization?

6. Does the use of cardiac treatment for patients with acute

MI differ for those with and without depression? Cardiac

treatment includes: revascularization (angioplasty or

bypass surgery), angiotensin converting enzyme (ACE)

inhibitors, beta blockers, statins, antiplatelet agents, or

other treatments recommended by the American Heart

Association or the American College of Cardiology.

Methods

The Johns Hopkins University Evidence-based Practice

Center (EPC) assembled a team including clinicians and

researchers from diverse specialties including cardiology,

psychiatry, general internal medicine, and cardiac rehabilitation.

The EPC team then recruited eight technical experts to provide

input regarding the choice of key questions. The expert review

panel consisted of a representative from the EPC’s partner

organization, the American Academy of Family Physicians, as

well as investigators active in post-MI depression research

including those from cardiology, psychiatry and psychology,

nursing, cardiac rehabilitation, and representatives of private

and governmental payers.

Literature Search

The EPC team performed a comprehensive search that

included electronic and hand searching. In March 2004, we

searched the following electronic databases: MEDLINE®, the

Cochrane CENTRAL® Register of Controlled Trials (Issue 1,

2003), the Cochrane Database of Methodology Reviews

(CDMR®), the Cumulative Index of Nursing and Allied

Health Literature (CINAHL®), the Psychological Abstracts

(PsycINFO®), and EMBASE®. 

Hand searching for possibly relevant articles was performed

by three techniques. First, the EPC team identified 16 journals

that we thought were most likely to contain relevant studies

and scanned the table of contents of each of these journals for

relevant citations from October 2003 to April 2004. Second,

we reviewed references cited in recent review articles for

inclusion. Third we examined the reference lists of eligible

articles for additional articles that might be relevant 

Two members of the EPC team independently reviewed the

abstracts identified by the search to exclude those that did not

meet the eligibility criteria. Primary studies were eligible if they

addressed one of the key questions, included original human

data, were not case reports, and were written in the English

language. Individual key questions had additional exclusion

criteria. When two reviewers agreed that an abstract was not

eligible, it was excluded from further review.

To focus the evidence report on the studies that would be

most valuable in addressing the key questions, we used the

following additional eligibility criteria:

• For key question 4 we excluded studies that did not

include a concurrent comparison group.

• For key question 5, we excluded studies that did not use a

validated reference standard.

Review Process

Paired reviewers assessed the quality of each eligible article.

Differences between the paired reviewers were resolved by faceto-face discussion. The reviewers assigned points for the quality

of the studies based on information about the

representativeness of the patients included in the study, the

potential for bias and confounding, the description of the

intervention or evaluation, the adequacy of followup, and the

appropriateness of the statistical methods. The score for each

category of study quality was the percentage of the total points

available in each category for that study, and could range from

zero to 100 percent.
One reviewer in each pair was the primary reviewer who

abstracted data from the article. The second reviewer confirmed

the accuracy of the first reviewer’s work.

Results

Key Question 1

In patients diagnosed with and hospitalized for acute MI

what is the prevalence of depression during initial

hospitalization for MI?

• Twenty-five articles met criteria for inclusion in this

review.1-5,9-27,48

• Articles were published between 1986 and 2004.

• Eight studies used a structured clinical interview,1-3,5,10,16,17,49

and 17 used a validated questionnaire. 4,5,9,11-15,18-25,50

• Major depression was reported in about one of every five

patients hospitalized for an MI. The reported prevalence

of potentially significant symptoms of depression varied

widely (range 10 to 47 percent).

• In general, the reported prevalence of potentially

significant symptoms of depression was higher when it

was based on a Beck Depression Inventory (BDI)5, 9,18-23,50

than when based on a Hospital Anxiety and Depression

Scale (HADS)12-15; this may be because the BDI includes

somatic symptoms that may overlap with MI symptoms,

whereas the HADS does not.

Key Question 1a. What is the prevalence of depression

during initial hospitalization for an acute MI, with and without

a history of previous depression as reported by study

investigators?

There was insufficient data to address this question.

Key Question 2

What percentage of patients with post-MI depression

continues to have depression (or depressive symptoms) one or

more months after initial hospital discharge? 

• We found 22 articles that met criteria for inclusion in this

review.

2,12,14,18-20,22,23,25,26,38,51-61

• Nine of the 22 used a standardized clinical interview to

diagnose depression.10,26,51-57

• Only three studies reported the prevalence of depression

in patients during the MI hospitalization and then

specifically re-assessed and reported the prevalence in these

same patients at followup.2,18,23

• Based on these three studies, most patients with

depression during the initial MI hospitalization continue

to have depression 1 to 4 months later.

Key Question 3

What is the association of post-MI depression with

outcomes independent of other predictors of post-MI

outcomes?

• Sixteen studies addressed the relationship of post-MI

depression and mortality.5-10,20,28-36

• Mortality has been assessed as early as 4 months5 and as

late as 10 years after MI.7

• The evidence indicates that post-MI depression is

associated with a significantly increased risk of death.

• A single study indicated that post-MI depression is

associated with increased cardiac re-admission in the first

year after MI.39

• Six studies reported on cardiac events in relationship to

post-MI depression.25,26,31,37-39 The three studies reporting a

positive relationship between post-MI depression and

cardiac events31,37,39 were generally larger than the three

studies finding no relationship25,26,38 suggesting that the

latter may have had insufficient power to detect

differences if they, in fact, were present.

• Depression during the initial hospitalization was related to

poor quality of life in the first year after MI.13,30,59,62

Key Question 3a. What is the association of post-MI

depression with surrogate markers of cardiac risk independent

of other predictors of post-MI outcomes?

• Three studies examined the association of post-MI

depression with heart rate variability, platelet activity, and

inflammatory markers (one study for each surrogate

marker).57,63,64

• All three studies reported surrogate markers of increased

risk in patients with post-MI depression, even after

adjustment for covariates.

Key Question 4

Do post-MI patients with depression have better outcomes

with depression treatment compared to those without

depression treatment?

• Twelve studies, 11 of which were randomized controlled

trials, addressed this question.10,40-47,65-67 The studies were

published between 1991 and 2003. 

• In post-MI patients with depression, psychosocial

intervention improves depression but not other

outcomes.10,44

3
4

• In post-MI patients with depression, selective serotonin

reuptake inhibitors improve depression and some

surrogate markers of cardiac risk, but no studies of

sufficient power address the question of whether this

treatment improves survival.45,46,65,66

Key Question 4a. Do outcomes differ with or without

improvement in depression for post-MI patients with

depression that do receive depression treatment?

There was insufficient data to address this question.

Key question 4b. Do outcomes differ with or without

improvement in depression for post-MI patients with

depression that do not receive depression treatment?

There was insufficient data to address this question.

Key Question 5

What are the performance characteristics (e.g., sensitivity,

specificity, reliability, and predictive value) of instruments or

methods that are used to screen for depression (or depressive

symptoms) following an acute MI?

• We found six studies published between 1968 and 1988

meeting criteria to address this issue.14,18,56,68-70

• Of the six studies, four were from Europe,14,56,68,70 one from

Canada18 and one from the United States.69

• All included studies reported exclusively on post-MI

populations.

• None of the instruments reported had been normalized

specifically for post-MI patients.

• The BDI tended to be more sensitive to lower levels of

depressive symptoms but less sensitive to more severe

depression compared to the HADS and the Symptom

Checklist-90 Depression scale.

Key question 5a. What are the performance characteristics

of instruments or methods that are used to screen for

depression (or depressive symptoms) following an acute MI

during hospitalization?

There was insufficient data to address this question.

Key question 5b. What are the performance characteristics

of instruments or methods that are used to screen for

depression (or depressive symptoms) following an acute MI,

within three months after hospitalization?

There was insufficient data to address this question.

Key Question 6

Does the use of cardiac treatment for patients with acute MI

differ for those with and without depression?

• Nine studies published between 1982 and 2004 met

criteria for review on this question. 23,26,37,50,71-75

• Four studies compared prescribed discharge medications

and were inconsistent in their findings: United States and

United Kingdom50,71 studies suggested decreased

prescriptions of beta-blockers and aspirin, while

European26 and Canadian23 studies found no difference.

• Three studies compared adherence to prescribed

medications and lifestyle modifications and consistently

found decreased adherence among depressed patients.71-73

• Two studies compared use of cardiac procedures and

reached divergent conclusions about the use of procedures

in post-MI patients.23,37

• Two studies assessed completion of cardiac rehabilitation

but had insufficient numbers to reach conclusions about

the influence of depression on completion of

rehabilitation.74,76

Discussion

Key Question 1

Major depression is reported in about one of every five

patients hospitalized for MI. This proportion is fairly consistent

among the eight studies that used a structured clinical interview

to establish this diagnosis. The reported prevalence of

potentially significant symptoms of depression varies more

widely (range 10 to 47 percent). This wide range of reported

prevalence rates appears to be due almost exclusively to

differences in measurement instruments used, and even to

differences in threshold criteria applied from study to study

when the same instrument was used. In general, the reported

prevalence of potentially significant symptoms of depression is

higher when this diagnosis is based on a BDI score of 10 or

higher than when it is based on a HADS score of either 8 or

higher or 11 or higher. This difference may be attributed to the

BDI’s inclusion of somatic symptoms that may overlap with

MI symptoms, whereas the HADS does not include somatic

symptoms and is designed for use in hospitalized patients. 

Additional studies also are needed to define the most

clinically-relevant measure of depression during the initial MI

hospitalization. Studies are needed to determine the clinical or

demographic factors that are associated with post-MI

depression.

Key Question 2

Although 22 studies reported the prevalence of depression in

patients 1 month or longer after initial hospital discharge, only
three reported the prevalence of depression in patients during

the MI hospitalization and then specifically reassessed and

reported the prevalence of depression in these same patients at

followup. These studies suggest that most patients (60 to 70

percent) with depression during the initial MI hospitalization

continue to have depression (or depressive symptoms) 1 to 4

months later.

Additional studies are needed that assess depression (or

depressive symptoms) in groups of patients during the initial

hospitalization and at various time points after MI. Studies of

patients who are reassessed for depression at multiple time

points post-MI are also needed.

Key Question 3

Sixteen studies evaluated the relationship between

depression, measured shortly after an acute MI, and subsequent

mortality. Studies have assessed this relationship as early as 4

months post-MI and as late as 10 years post-MI. Despite the

facts that various measures of depression have been used, that

different subgroups of depressed patients have been evaluated,

and that different post-MI survival times have been assessed,

the weight of the evidence is strikingly consistent. Overall, the

evidence supports the notion that post-MI depression is

associated with a significantly increased risk for subsequent

death, whether by cardiac or other causes. Depression appears

to be associated with about a 3-fold increased risk of cardiac

mortality per se based on at least three studies that addressed

cardiac mortality in a total of almost 2,000 patients.39,77,78

Depression during the initial hospitalization is associated with

poor quality of life in the first year after an MI.

During the first year after MI, depression during the initial

MI hospitalization has been found to be inversely related to

physical quality of life, social quality of life of women, sexual

activity and satisfaction among men, return to work of

employed men, and to physical, psychological, and social health

and function. Limitations of the above mentioned studies

included the variety of diagnostic instruments used to assess

depression; the lack of agreement on what aspects of quality of

life are of greatest import or how to measure included studies;

the degree to which potential confounders were adequately

considered; and the absence of data in early post-MI time

points.

Additional studies are needed to determine the major

cause(s) of mortality among depressed post-MI patients.

Additional studies also are needed to determine whether

patients with depression are at higher risk for malignant

arrhythmias than comparable post-MI patients without

depression.

Key question 3a. A small amount of evidence suggests that

post-MI patients with depression have alterations in autonomic

function as reflected by decreased heart rate variability,

increased platelet activity, and increased levels of soluble

adhesion molecule 4. These studies suggest that the risk

associated with post-MI depression could be transmitted by

multiple biological pathways.

Additional studies are needed to elucidate the mechanism(s)

responsible for increased mortality in patients with post-MI

depression. Particular emphasis should be placed on surrogate

markers which have been previously associated with increased

risk without regard to depression, including markers for sudden

death including heart rate variability, T-wave alternans, etc, and

inflammatory markers including C-reactive protein,

interleukins, adhesion molecules and others. Studies are needed

that evaluate the hemostatic and platelet function of patients

with post-MI depression. Future studies also should address

whether responses to commonly used antiplatelet agents differ

among post-MI patients with versus without depression.

Key Question 4

No studies of sufficient power have yet been performed that

directly address the question as to whether treatment with

antidepressants improves survival in depressed patients after an

MI. Some evidence suggests that selective serotonin reuptake

inhibitor antidepressants have beneficial effects on surrogate

markers of post-MI risk (e.g., heart rate variability, aortic time

velocity integral). There is evidence that both psychosocial

intervention and selective serotonin reuptake inhibitor

antidepressants improve depression in post-MI patients.

However, the possibility of increases in rare adverse events

cannot be excluded. 

Studies are needed to determine whether patients with

depression who are treated for depression, especially with highly

effective drugs, differ in outcomes from patients who are not

treated. Future studies should also determine whether treatment

for depression per se or resolution of depression is associated

with different outcomes.

Key Question 5

There are insufficient data to allow an adequate assessment

of the performance characteristics of instruments or methods

used to screen for depression during the initial MI

hospitalization. The very low positive predictive values of these

screening instruments (generally in the 25 to 50 percent range)

may be acceptable clinically if followed by a more thorough

assessment of those who screen positive; however, the low

positive predictive values are particularly problematic if used to

detect relationships to outcome variables in the research setting.

When compared with the HADS and Symptom Checklist-90

5
Depression scale, the BDI tends to diagnose less significant

symptoms of depression at higher rates. It may be less effective

in accurately diagnosing major depression.

Additional studies are needed to determine the performance

characteristics of instruments or methods used to screen for

depression (or depressive symptoms) during the initial MI

hospitalization. Studies are needed in post-MI patients that

examine the ability for depression screening instruments or

methods to distinguish symptoms of depression from

symptoms attributable to the MI, to poor physical health, or to

the hospitalization itself.

Key Question 6

It remains unclear whether there are significant differences in

cardiac medications prescribed to post-MI patients based on

the presence or absence of depression. Three studies evaluated

adherence to prescribed medications and secondary prevention

measures in post-MI patients and consistently found lower

adherence in those with depression than those without

depression. Two good-quality studies, using different methods,

came to diverse conclusions about whether the frequency with

which cardiac procedures are used varies between post-MI

patients with depression and those without depression. 

Additional large studies are needed to examine whether the

use of diagnostic and therapeutic procedures differs between

depressed and non-depressed post-MI patients. Future studies

should also address whether potential differences in procedures

are due to differences in provider recommendation or to

differences in patient acceptance. Further studies are needed to

determine whether the treatment prescribed to post-MI

patients with depression differs from those without depression.

Future studies should address whether the non-pharmacologic

interventions (including diet, exercise and cardiac

rehabilitation) recommended to post-MI patients differ

between those patients with and without post-MI depression.

Future studies should examine the adherence behavior of postMI patients and evaluate measures that could improve

adherence to recommended treatment.

Availability of the Full Report

The full evidence report from which this summary was taken

was prepared for the Agency for Healthcare Research and

Quality (AHRQ) by The Johns Hopkins University Evidencebased Practice Center under Contract No. 290-02-0018. It is

expected to be available in spring 2005. At that time, printed

copies may be obtained free of charge from the AHRQ

Publications Clearinghouse by calling 800-358-9295.

Requesters should ask for Evidence Report/Technology

Assessment No. 123, Post-Myocardial Infarction Depression. In

addition, Internet users will be able to access the report and this

summary online through AHRQ’s Web site at www.ahrq.gov.

Suggested Citation

Bush DE, Ziegelstein RC, Patel UV, Thombs BD, Ford DE,

Fauerbach JA, McCann UD, Stewart KJ, Tsilidis KK, Patel AL,

Feuerstein CJ, Bass EB. Post-Myocardial Infarction Depression.

Summary, Evidence Report/Technology Assessment No. 123.

(Prepared by the Johns Hopkins University Evidence-based

Practice Center under Contract No. 290-02-0018.) AHRQ

Publication No. 05-E018-1. Rockville, MD: Agency for

Healthcare Research and Quality. May 2005.

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