New frontiers in cardiovascular behavioral medicine: Comparative effectiveness of exercise and medication in treating depression

EXERCISE THERAPY FOR DEPRESSION

Some studies of exercise treatment for CHD patients have tracked depressive symptoms and thus have provided information regarding the potential efficacy of exercise as a treatment for depression in this population.^{76 –81} Although most previous studies have reported significant improvements in depression after completion of an exercise program, many studies had important methodologic limitations, including the absence of a control group.

In one of the few controlled studies in this field, Stern et al⁸² randomized 106 male patients who had a recent history of AMI along with elevated depression and anxiety or low fitness to 12 weeks of exercise training, group therapy, or a usual-care control group. At 1-year followup, both the exercise and counseling groups showed improvements in depression relative to controls.

Cross-sectional studies of non-CHD samples have reported that active individuals obtain significantly lower depression scores on self-report measures than sedentary persons.⁸³ Studies also have shown that aerobic exercise may reduce self-reported depressive symptoms in nonclinical populations and in patients diagnosed with MDD.⁸³ In 2001, a meta-analysis evaluating 11 randomized controlled trials of non-CHD patients with MDD⁸⁴ noted that studies were limited because of self-selection bias, absence of control groups or nonrandom controls, and inadequate assessment of exercise training effects; the authors concluded that “the effectiveness of exercise in reducing symptoms of depression cannot be determined because of a lack of good quality research on clinical populations with adequate followup.”

Randomized controlled trials needed

A subsequent meta-analysis⁸⁵ included 25 studies; for 23 trials (907 participants) that compared exercise with no treatment or a control intervention, the pooled standardized mean difference (SMD) was −0.82 (95% CI, −1.12, −0.51), indicating a large effect size. However, when only the three trials (216 participants) with adequate allocation concealment, intention to treat analysis, and blinded outcome assessment were included, the pooled SMD was −0.43 (95% CI, −0.88, 0.03), with a point estimate that was half the size of that with all trials. As a result, the authors concluded that “exercise seems to improve depressive symptoms in people with a diagnosis of depression, but when only the methodologically robust trials are included, the effect size is only moderate.”

To date, no randomized clinical trials (RCTs) have examined the effects of exercise on clinical outcomes in depressed cardiac patients. However, data from the ENRICHD trial suggest that exercise may reduce the rates of mortality and nonfatal reinfarction in patients with depression or in post-MI patients who are socially isolated.⁸⁶ Self-report data were used to categorize participants as exercising regularly or not exercising regularly. After controlling for medical and demographic variables, the magnitude of reduction in risk associated with regular exercise was nearly 40% for nonfatal reinfarction and 50% for mortality. The evidence that exercise mitigates depression, reduces CHD risk factors, and improves CHD outcomes suggests that exercise may be a particularly promising intervention for depressed CHD patients.

COMPARATIVE EFFECTIVENESS OF EXERCISE AND ANTIDEPRESSANT MEDICATION

In 2008, an Institute of Medicine (IOM) report called for a national initiative of research that would provide a basis for better decision-making about how to best treat various medical conditions, including depression. In 2009, the American Reinvestment Recovery Act provided a major boost in funding for comparative effectiveness research (CER). The act allotted $1.1 billion to support this form of research. CER refers to the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, or to improve the delivery of care. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers in reaching informed decisions that will improve health care at both the individual and population levels.⁸⁷

Two research categories inform decision-making

Two broad categories of research have been used to inform decision-making:

• Epidemiologic studies provide evidence linking various treatments with patient outcomes. These sources of data are limited because they seldom specify the basis for medical decisions and they fail to consider patient characteristics that affect both clinical decisions and clinical outcomes. Indeed, it has been suggested that “overcoming the limitations of observational research is the most important frontier of research on study methods.”⁸⁸
• RCTs address these limitations by randomly assigning patients to different treatment conditions. While this design may eliminate some of the uncertainty and potential confounders that characterize purely observational studies, most RCTs are efficacy studies; patients are carefully selected and a treatment is usually compared with a placebo or usual care.

The RCT design addresses the question of whether a given treatment is effective, but it does not necessarily address questions that many physicians want answers to: namely, is this treatment better than that treatment? Further, physicians want to know if one treatment is more effective than another for a given patient. For example, Hlatky et al⁸⁹ showed that mortality associated with percutaneous coronary interventions (PCIs) and CABG surgery was comparable; however, mortality with CABG surgery was significantly lower for patients older than 65 years while PCI was superior for patients younger than 55 years. Thus, examination of individual differences may also help to inform clinicians about the optimal therapy for their particular patients.