Summary
Evidence Report/Technology Assessment: Number 123
Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) is developing scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools. Contractor institutions review all relevant scientific literature on assigned clinical care topics and produce evidence reports and technology assessments, conduct research on methodologies and the effectiveness of their implementation, and participate in technical assistance activities.
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Introduction / Methods / Results / Discussion / Availability of Full Report / References
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.
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:
- 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.
- 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?
- What percentage of patients with post-MI
depression continue to have depression (or
depressive symptoms) one or more months
after initial hospital discharge?
- What is the association of post-MI
depression with outcomes independent of
other predictors of post-MI outcomes? Post-MI 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.
- 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.
- 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.
- Do outcomes differ with or without improvement in
depression for post-MI patients with depression that
do receive depression treatment?
- Do outcomes differ with or without improvement in
depression for post-MI patients with depression that
do not receive depression treatment?
- 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?
- 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?
- 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?
- 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.
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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 face-to-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.
- 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.
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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
- 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
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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:
- Variety of diagnostic instruments used to assess depression.
- 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.
- 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 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 post-MI patients and evaluate measures that could improve
adherence to recommended treatment.
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Availability of 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 Evidence-based
Practice Center under Contract No. 290-02-0018. 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.
The Evidence Report is also online on the National Library of Medicine Bookshelf, or can be downloaded as a PDF File (1.8 MB). PDF Help.
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AHRQ Publication Number 05-E018-1
Current as of May 2005
Internet Citation:
Bush DE, Ziegelstein RC, Patel UV, et al. Post-Myocardial Infarction Depression. Summary, Evidence Report/Technology Assessment: Number 123. AHRQ Publication Number 05-E018-1, May 2005. Agency for Healthcare Research and Quality, Rockville, MD. http://www.ahrq.gov/clinic/epcsums/midepsum.htm