Depression and cardiovascular disease: Selected findings, controversies, and clinical implications from 2009
ABSTRACT
We systematically searched published empirical research on depression and cardiovascular disease (CVD) and found 494 unique articles published in 2009. Several particularly notable and provocative findings and controversies emerged from this survey of the 2009 literature. First, multiple large observational studies found that antidepressant use was associated with increased risk of incident stroke, CVD, or sudden cardiac death. Second, four randomized controlled trials on depression interventions in CVD patients reported important efficacy results that should guide future trials. Finally, the vigorous debate on whether patients with CVD should be routinely screened (and subsequently treated) for depression continued in 2009 even as some observed that routine screening for CVD in depressed patients is more evidence-based and appropriate. This article reviews these selected provocative findings and controversies from our search and explores their clinical implications.
Summary and clinical implications
Each of these four efficacy trials adds critical information to the evidence base. Depressed patients who have undergone CABG can be effectively treated in primary care settings with integrative care,17 and CBT is also extremely effective for these patients.18 Additional studies of omega-3 supplementation should not be pursued at this time, but using a run-in period to better identify patients who are prepared to engage in treatment is a prudent idea and should be used in future trials in this area.19 Patients with CHD and persistent depressive symptoms are a promising group to target for depression therapy, and asking patients to choose their type of depression treatment may improve response to therapy for both depression and CHD.20
DEPRESSION SCREENING, REFERRAL, AND TREATMENT IN PATIENTS WITH CVD
We finish with the least evidence-based and most controversial issue in the area of depression and CVD. This controversy started in 2008 when the American Heart Association recommended in an advisory (endorsed by the American Psychiatric Association) that “screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment” if appropriate referral for further depression assessment and treatment is available.21 Partly in response to this advisory, Thombs et al conducted a systematic review of the evidence on whether screening or treatment improves outcomes of depression or CVD in patients with CVD.22 They found no trial that tested whether depression screening was beneficial in patients with CVD, and the randomized controlled trials of depression treatment provided evidence of only mild improvement of depressive symptoms and no improvement in CVD outcome. Therefore, they questioned whether routine depression screening was appropriate.22
In at least eight editorials, letters, and reviews published on this subject in 2009, investigators continued to debate this issue.23–30 Below we provide a simplified list of reasons presented for and against screening and subsequent treatment raised in these articles.
Arguments for depression screening and treatment
The proponents of screening contend that depression is highly prevalent in patients with CVD and is clearly a risk marker for increased adverse events, reduced quality of life, and poorer adherence to treatment.24 They argue that since there are plausible biologic and behavioral mechanisms for this association, and since SSRI use improves depressive symptoms in other patient populations and is safe in patients with CVD, health care providers should not hesitate to screen and refer patients for appropriate depression treatment. At the same time, they have cautioned that SSRIs interact with anti coagulants and that bleeding should be monitored closely in patients with CVD who are taking SSRIs.24
Whooley28 noted that although there are controversial findings in this area, depression screening provided in conjunction with collaborative care depression management is cost-effective and has a documented positive impact on depression, if not on CVD outcomes.17,31 She observed that there are some costs to screening, such as false-positive findings (resulting in stigma for patients incorrectly diagnosed) and diversion of resources from other health care needs. However, Whooley suggested that primary care providers, rather than cardiologists, should conduct depression screening and that patients should undergo screening only when an established collaborative care treatment protocol exists.28
Carney et al argued that depression, like age, clearly marks CVD risk, and that health care providers should aggressively treat readily modifiable CVD risk factors.23 They added that because of the strong association between depression and medication nonadherence,32 providers should carefully monitor patient adherence to life-saving therapies.
Taking another tack, Shemesh and colleagues advocated the importance of documenting the prevalence of suicidal ideation and intent if recommendations to screen for depression in CVD patient populations were implemented.25 Using a sample of more than 1,000 patients with CVD, they determined the prevalence of suicidal ideation (12.0%) and the number of patients who required hospitalization for risk of suicide (0.5%) when routine depression screening occurred in a large cardiology clinic. They concluded that identification and stabilization of imminently suicidal patients would be a benefit of universal screening and that there is a high societal cost to neglecting suicidal ideation, intent, and risk in patients with CVD. However, more patients would need immediate thorough psychiatric evaluations for safety, which would affect resource allocation and cost in cardiology clinics.
Arguments against depression screening and treatment
The main argument against screening for and treating depression in patients with CVD is that there are neither randomized controlled trials nor systematic evidence-based reviews showing that screening for depression and/or referring for additional treatment sufficiently improves outcomes for depression or CVD, and that existing evidence does not support the recommendation to screen all patients with CVD.22,30 Furthermore, antidepressant use is associated with only mild improvement in depressive symptoms, even in other patient populations,33 and publication bias (“the file-drawer problem”) has prevented the publication of antidepressant trials with null results, thereby skewing the evidence base.34 In addition, considerable health care resources would be needed to mount such a large screening effort, and these resources would come at the expense of other efforts. Finally, the adverse effects of medications and the inevitability of some false-positive screening results must be weighed against any benefit that might occur with universal screening.35
In addition to the arguments above, Ziegelstein et al,29 in commenting on the American Heart Association advisory,21 wryly observed that there is far greater observational evidence that depressed patients seen in mental health settings are at risk for incident and recurrent CVD and that there should be universal screening and referral for CVD in patients with depression. They contended as well that the evidence is insufficient to recommend that patients with CVD undergo universal depression screening and referral.
Summary and clinical implications
Although we were hesitant to raise this tense and often emotional issue, we are in favor of routine, algorithm-based depression screening by all cardiologists, with the critical proviso that a nationwide and/or Centers for Medicare and Medicaid Services–coordinated randomized controlled trial be conducted to evaluate this practice. All patients with pronounced depressive symptoms should be referred to the trial, and two depression treatments should be evaluated, such as usual referral versus telephone-based collaborative care17 or enhanced depression care.20 Such a trial would allow us to ensure that data are collected on the cost,36 the benefit, and even the possible harms associated with routine depression screening for patients with CVD, and we could ascertain if there is an acceptable, beneficial treatment for depression that can be delivered and definitively tested.
