New frontiers in cardiovascular behavioral medicine: Comparative effectiveness of exercise and medication in treating depression
ABSTRACT
Exercise, considered a mainstay of cardiac rehabilitation, has been shown to reduce cardiac risk factors such as hyperlipidemia and hypertension. Growing evidence also suggests that exercise has beneficial effects on mental health, which is relevant for cardiac patients because of the prognostic significance of depression in patients with coronary heart disease (CHD). Depression has been associated with increased mortality and nonfatal cardiac events in patients with CHD; it is also associated with worse outcomes in patients who undergo coronary artery bypass graft surgery and those who have heart failure. The standard therapy for depression is pharmacologic treatment, often with second-generation antidepressants such as selective serotonin reuptake inhibitors. Despite their widespread use, antidepressants have only modest effects on depression for many patients compared with placebo controls. Exercise therapy, already an established component of cardiac rehabilitation, has potential efficacy as a treatment for depression in cardiac disease patients. Randomized controlled trials are needed to determine the clinical effects of exercise in this population and to compare the effects of exercise with those of antidepressants.
Treatment of depression not necessarily a research priority
The IOM committee sought advice from a broad range of stakeholders and prioritized areas for research. The top-ranked topic was comparison of treatment strategies for atrial fibrillation, including surgery, catheter ablation, and pharmacologic treatment. Coming in at #98 was comparison of the effectiveness of different treatment strategies (eg, psychotherapy, antidepressants, combination treatment with case management) for depression after MI and their impact on medication adherence, cardiovascular events, hospitalization, and death.
In a second Duke study that compared exercise and antidepressant medication,92 202 adults (153 women; 49 men) diagnosed with MDD were randomly assigned to one of four groups: supervised exercise in a group setting, home-based exercise, antidepressant medication (sertraline, 50 to 200 mg daily), or placebo pill for 16 weeks. Once again, patients underwent the Structured Clinical Interview for Depression and completed the HAM-D. After 4 months of treatment, 41% of participants achieved remission, defined as no longer meeting criteria for MDD and a HAM-D score of less than 8 points. Patients receiving active treatments tended to have higher remission rates than placebo controls: supervised exercise, 45%; home-based exercise, 40%; medication, 47%; placebo, 31% (P = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (P = .23). However, when immediate responders (ie, those patients who reported more than 50% reduction in depressive symptoms after only 1 week of treatment) were excluded from the analysis, patients receiving active treatments (ie, either sertraline or exercise) had greater reductions in depressive symptoms compared with placebo controls (P = .048). There was no difference between the exercise and antidepressant groups. We concluded that the efficacy of exercise appears generally comparable with antidepressant medication and both tend to be better than placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response could be determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors. Similar to our previous trial, participants who continued to exercise following the completion of the program were less likely to be depressed.93
Another RCT94 also demonstrated that exercise was associated with reduced depression, independent of group support. Participants exercised alone in a secluded setting, and the study included a no-treatment control group. Only 53 of 80 patients actually completed the 12-week trial, however, including only five of 13 no-treatment controls. Moreover, there was no active treatment comparison group, so that an estimate of comparative effectiveness could not be determined.
While these results are preliminary and should be interpreted with caution, it appears that exercise may be comparable with conventional antidepressant medication in reducing depressive symptoms, at least for patients who are willing to try it, and maintenance of exercise reduces the risk of relapse.
SUMMARY
Three decades ago, we recognized that CR was a new frontier for behavioral medicine. We now know that successful rehabilitation of patients with CHD involves modification of lifestyle behaviors, including smoking cessation, dietary modification, and exercise. Exercise is no longer considered unsafe for most cardiac patients, and exercise is currently the key component of CR services. Research also has provided strong evidence that depression is an important risk factor for CHD, although there is no consensus regarding the optimal way to treat depression in CHD patients.95 Research on comparative effectiveness of established and alternative treatments for depressed cardiac patients is a new frontier for future pioneers in heart-brain medicine.
