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Bush DE, Ziegelstein RC, Patel UV, et al. Post-Myocardial Infarction Depression. Rockville (MD): Agency for Healthcare Research and Quality (US); 2005 May. (Evidence Reports/Technology Assessments, No. 123.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Post-Myocardial Infarction Depression.

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4Discussion

Conclusions and Limitations

1.

In patients hospitalized for acute MI what is the prevalence of depression during the initial hospitalization for MI?

Important technical and methodological issues affect the interpretation of studies that address this question. These issues include variations from study to study in (1) the definition of “depression” (modified major depression versus potentially significant symptoms of depression versus definition not specified), (2) the screening instrument or method of diagnosis employed, and (3) the clinical threshold criteria (i.e., cutoffs) used even with the identical screening instrument.

Major depression is reported in about one of every five patients hospitalized for MI. This proportion is fairly consistent among the seven studies that used a SCID 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. Although it is difficult to draw conclusions from small numbers of studies and different assessment methods, the variability in reported prevalence does not appear to be explained by differences in demographic characteristics such as age and sex.

Of note, although the reported prevalence of potentially significant symptoms of depression varies fairly widely from 10 to 47 percent, closer inspection suggests less variability in actual prevalence rates. The study that reported a prevalence rate of 47 percent was the only study that used the revised version of the BDI-II79 This study was reported in brief format (i.e., as a “Scientific letter”) and without key demographic information. Of the five studies that used a cutoff score of 10 or higher on the BDI,25, 77, 78, 80, 81 four reported prevalence rates between 32 and 37 percent. The sample size of the study that reported a prevalence rate of 21 percent80 was relatively small (85 patients).

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.

1a.

What is the prevalence of depression during initial hospitalization for MI in patients with or without a known history of depression as reported by study investigators?

Study investigators reported information about a history of depression in only two studies, and neither provided separate prevalence data for these patients. There is therefore insufficient evidence to address this question.

2.

What percentage of patients with post-MI depression continue to have depression (or depressive symptoms) 1 month or longer after initial hospital discharge?

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 follow-up.

These studies suggest that most patients (60–70 percent) with depression during the initial MI hospitalization continue to have depression (or depressive symptoms) 1 to 4 months later.

3.

What is the association of various measures of depression with outcomes in patients with acute MI, independent of known predictors of post-MI outcomes?

Seventeen 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 four studies that addressed cardiac mortality in a total of almost 2,000 patients.22, 23, 100

Six studies evaluated the relationship between depression and cardiac events. The study that examined the relation between depression during the initial MI hospitalization and cardiac readmission106 suggests depression is associated with increased cardiac readmission during the first year, even after controlling for important cardiac variables. That there may be a relation between post-MI depression and cardiac events is indicated by three studies that evaluated this association.84, 89, 95 Strik et al. found a relation between depression and cardiac events in one study.84 However, this relation was not significant after anxiety was added to the model. Shiotani et al.95 evaluated a much larger sample and found a trend toward a multivariate relationship between post-MI depression and cardiac events for patients younger than 65 years and a significant multivariate relationship in those older than 65. None of these three studies presented data on the statistical power to detect differences in cardiac events given the sample sizes. Given the relatively low cardiac event rates, the sample sizes of the studies that did not find a significant independent relation between depression and cardiac events84, 89 were relatively small compared with the larger sample size of the studies of Shiotani et al.95 and Frasure-Smith et al.106

During the first year after MI, depression during the initial MI hospitalization has been found to be inversely related to physical QOL, social QOL of women, sexual activity and satisfaction among men, return to work of employed men, and to physical, psychological, and social health and function. Studies show that even as long as 5 years after an MI, in-hospital depression can have a prolonged negative impact on psychological distress and physical health and functioning.

Limitations of the above-mentioned studies included the variety of diagnostic instruments used to assess depression (some of which were not categorical or diagnostic, but continuous in nature); the lack of agreement on what aspects of QOL are of greatest import or how to measure them; limits in the power to draw firm conclusions, based on the small number of subjects included in studies; the degree to which potential confounders were adequately considered; the question of whether it is appropriate to adjust for symptoms of fatigue when analyzing the association between depression and clinical outcomes after an MI; and the absence of data in early post-MI time points (e.g., 30 days).

3a.

What is the association of various measures of depression with surrogate markers of cardiac risk in patients with acute MI, independent of known predictors of post-MI outcomes?

Three studies have been performed in post-MI patients to compare HRV, platelet-derived substances, and inflammatory markers in those with and those without depression. All three studies reported differences in at least one surrogate marker between patients with a major depressive syndrome post-MI compared with post-MI groups without depression. All three studies found surrogate markers of increased risk in the patients with post-MI depression. The higher risk profile in all surrogate markers persisted after adjustment for covariates. Thus, a small amount of evidence suggests that post-MI patients with depression have alterations in autonomic function as reflected by decreased HRV, 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.

Few studies have evaluated these surrogate markers in post-MI patients with depression and compared them to post—MI patients without depression. All studies have compared only patients with major depressive syndrome to those without major depression. It is unknown whether other forms of depression are also associated with similar changes in these biomarkers.

4.

Do post-MI patients with depression have better outcomes with depression treatment than do those without such treatment?

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. However, there is evidence that SSRI antidepressants do not have common adverse cardiac effects when administered to early post-MI patients. Increases in rare adverse effects cannot be excluded. Some evidence suggests that SSRI antidepressants have beneficial effects on surrogate markers of post-MI risk (e.g., HRV, aortic time velocity integral).

There is evidence that both psychosocial intervention and SSRI antidepressants improve depression in post-MI patients. However, the possibility of increases in rare adverse events cannot be excluded. Current clinical trial evidence suggests psychosocial interventions do not improve post-MI cardiac outcomes.

5.

What are the performance characteristics (e.g., sensitivity, specificity, and predictive value) of instruments or methods that are used to screen for depression (or depressive symptoms) after MI?

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.

HAMD has adequate sensitivities and specificities for identifying depression within 3 months after hospitalization for an MI, as compared to a diagnosis of depression based on a SCID. There is also evidence for convergent validity and adequate internal consistency.

None of these measures has been normalized specifically in post-MI populations. It is unclear how well these instruments distinguish symptoms of depression from somatic symptoms related to the MI, to poor physical health, or to the hospitalization itself.

The very low PPVs 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 PPVs are particularly problematic if used to detect relationships to outcome variables in the research setting. The study that generated diagnostic utility figures used cutoffs that were slightly lower than those commonly employed in research studies. If the more commonly-used cutoffs had been employed, PPVs would have been slightly higher.

When compared with the HADS, SCL-90-Dep, and HAMD, the BDI tends to diagnose less significant symptoms of depression at higher rates,. It may be less effective in accurately diagnosing major depression.

Important questions remain and further research is needed to improve performance. This research should include more sophisticated analyses of existing measures as well as the potential development of new measurement techniques specifically validated for use with MI survivors.

6.

Does the use of cardiac treatment for patients with acute MI differ for those with and those without depression?

Four studies included in this review evaluated whether the use of medications for the secondary prevention of adverse cardiac events post-MI differs between depressed and nondepressed patients. The findings of these studies were inconsistent. Two studies found that beta-blockers were prescribed less frequently among post-MI patients with depression than among post-MI patients without depression. One study found that aspirin or antiplatelet agents were used less frequently in depressed than nondepressed post-MI patients. Finally, one study found no difference in the use of any recommended medication between depressed and nondepressed post-MI patients. Thus, 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.

Two small studies examined participation in post-MI cardiac rehabilitation programs and reported discordant results. No conclusion can be reached about the likelihood of patients completing cardiac rehabilitation programs based on the presence or absence of post-MI depression.

Future Research

1.

In patients hospitalized for acute MI, what is the prevalence of depression during the initial hospitalization for MI?

Additional studies are needed to define the most clinically relevant measure of “depression” during the initial MI hospitalization. The definition of depression varies considerably from study to study; to determine the most appropriate definition in this setting, clinical relevance should be determined for each definition.

Studies are needed to determine the clinical or demographic factors that are associated with post-MI depression. Given the episodic nature of depression, future studies on this topic should carefully document which patients have had depression diagnosed and/or treated in the past and which patients report significant depressive symptoms in the past that might not have been formally diagnosed or treated.

2.

What percentage of patients with post-MI depression continue to have depression (or depressive symptoms) 1 month or longer after initial hospital discharge?

Additional studies are needed that assess depression (or depressive symptoms) in groups of patients during the initial hospitalization and at various times after MI. In particular, the group of patients with depression (or depressive symptoms) during the initial MI hospitalization should be reassessed at certain time points after discharge.

3.

What is the association with various measures of depression with outcomes in patients with acute MI, independent of known predictors of post-MI outcomes?

Additional studies are needed to determine the major cause(s) of mortality among depressed post-MI patients and whether these causes differ in distribution from nondepressed post-MI patients. Additional studies also are needed to determine whether patients with depression are at higher risk for malignant arrhythmias than are comparable post-MI patients without depression.

3a.

What is the association of various measures of depression with surrogate markers of cardiac risk in patients with acute MI, independent of known predictors of post-MI outcomes?

Additional studies are needed to elucidate the mechanism(s) responsible for increased mortality in patients with post-MI depression. Additionally, studies which establish the time after an MI at which the adverse effects of depression on post-MI outcomes first become evident may yield important indirect insights into potential mechanisms involved.

Studies that evaluate the hemostatic and platelet function of patients with post-MI depression are needed. Studies also should address whether responses to commonly used antiplatelet agents differ between post-MI patients and those without depression.

4.

Do post-MI patients with depression have better outcomes with depression treatment than those without such treatment?

Additional studies are needed which evaluate this question. There are actually three questions within this larger question. The first is whether cardiac outcomes are better if depression is successfully treated. The second question is whether cardiac outcomes are better with antidepressant treatment regardless of whether depression improves. The third question is whether cardiac outcomes are better if depression resolves with antidepressant treatment compared to spontaneous resolution. None of these questions has been adequately addressed by the existing literature.

5.

What are the performance characteristics of instruments or methods that are used to screen for depression (or depressive symptoms) after MI?

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.

6.

Does the use of cardiac treatment for patients with acute MI differ for those with 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. Studies should also address whether potential differences in procedures are due to differences in providers' recommendations or to differences in patients' acceptance. Further studies also are needed to determine whether the treatment prescribed for post-MI patients differs between those with and those without 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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