EDITORIAL COMMENT

Exercise as Medical
Treatment for Depression*
Alan Rozanski, MD
New York, New York
Major depression is a now well-established risk factor for
cardiovascular disease (CVD), comparable in potency with
conventional risk factors (1). Epidemiological study has
demonstrated a proportional relationship between the severity
of depressive symptoms and the likelihood of subsequent
cardiac events, and patients with even mild depressive symp-
toms have been noted to have an increase in mortality risk
compared with patients without depression (2,3). The mech-
anisms by which depression causes CVD fall into 2 general
categories: a higher concentration of poor health habits such as
smoking, physical inactivity, and medication noncompliance in
depressed patients and direct pathophysiological effects (4).
See page 1053
Chronic depression is associated with persistent activation of
both the sympathetic nervous system and the hypothalamic-
pituitary-adrenal axis, with resultant development of auto-
nomic, endothelial, platelet, and ovarian dysfunction, elevation
in inammatory proteins, and increased risk for diabetes (1,4).
Depression also impairs cognitive function and adversely alters
brain plasticity, although there are indications that these
changes are not irreversible.
The relationship between depression and CVD is bidi-
rectional. Just as depression increases the risk for CVD, the
development of CVD increases the risk for depression. As a
consequence, the prevalence of depressive symptoms in
cardiac populations is more than 30%, and approximately
15% of cardiac patients manifest major depression, a rate
that is 3-fold higher than the point prevalence for depres-
sion within the general community (4).
Consequently, there has been growing interest in devel-
oping treatment strategies that effectively reduce depression
among cardiac patients. In general, patients with depression
can be treated by specic types of psychotherapy, such as
cognitive therapy or interpersonal psychotherapy, and/or by
use of antidepressant medications, primarily selective sero-
tonin reuptake inhibitors (SSRIs). Whereas psychotherapies
have been shown to be effective for treating mild to
moderate depression, their use among cardiac patients with
comorbid depression is in need of further study. Cognitive
therapy, which is based on the concept that the quality of
our thoughts affects our emotions, focuses on identifying
present distortions in thoughts and behavior patterns and
acquiring tools to change them. Whereas cognitive therapy
may be particularly apt for short-term therapy, to date,
only 1 large study, the ENRICHD (Enhancing Recovery
in Coronary Heart Disease) trial, studied cognitive ther-
apy in cardiac patients, with randomization of 2,481
postmyocardial infarction patients to either cognitive
therapy or usual care. During a mean follow-up period of
29 months, no mortality difference was noted with cognitive
therapy versus usual care, and cognitive therapy produced
only modestly greater reduction in depression symptoms (5).
A second randomized study did not nd improvement in
depressive symptoms with interpersonal psychotherapy ver-
sus usual care in cardiac patients (6).
SSRIs are widely used by internists, general practitioners,
and psychiatrists to treat both mild and severe depression
and have been demonstrated to have an acceptable safety
prole among cardiac patients (7). However, there is limited
evidence that cardiac outcomes in patients with depression and
cardiac disease are improved by SSRIs. In the ENRICHD
study, a secondary ad hoc analysis found that SSRI use was
associated with reduced mortality during follow-up (8). The
few other prospective studies have involved small sample
sizes and yielded conicting results, and a meta-analysis of
randomized trials to date demonstrated no signicant prog-
nostic benet for SSRI use (9). Thus, more study in this
arena is also required.
Exercise as Antidepressant Treatment
In this issue of the Journal, Blumenthal et al. (10) now assess
exercise training as a third way to treat depression in cardiac
patients. Physiologically, exercise training can increase pre-
frontal cortex blood ow (11) and hippocampal volume (12)
and increase brain mediators such as brain-derived neutro-
trophic factor (which may be a key feature of depression)
(13). Regular exercise enhances executive function, learning,
and retention and serves as a protector against the develop-
ment of dementia (11,12,14). Epidemiologically, cross-
sectional studies, such as the Alameda County Study (15),
have found a lower frequency of depressive symptoms
among community dwellers who exercise versus those who
do not. Longitudinal studies that have measured physical
activity levels at baseline and then followed subjects over
time have also found relatively lower levels of subsequent
depressive symptoms among those who were physically
active at baseline (16). Subsequent studies have assessed the
prospective reduction in depression after formal exercise
*Editorials published in the Journal of the American College of Cardiology reect the
views of the authors and do not necessarily represent the views of JACC or the
American College of Cardiology.
From the Division of Cardiology, St. Lukes-Roosevelt Hospital Center, and the
Department of Medicine, Columbia University College of Physicians and Surgeons,
New York, New York. Dr. Rozanski has reported that he has no relationships relevant
to the contents of this paper to disclose.
Journal of the American College of Cardiology Vol. 60, No. 12, 2012
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training. A recent meta-analysis of 25 randomized studies
that compared exercise with standard treatment for depres-
sion, no treatment, or placebo found a large treatment effect
for exercise (17). However, the investigators also noted the
relatively poor design of many of the studies included in this
meta-analysis. Hence, there is a need for more well-
designed prospective studies, such as the present study by
Blumenthal et al. (10).
The investigators randomized 101 patients with vari-
ous degrees of depression into 3 treatment groups:
sertraline (50 to 200 mg), group exercise 3 times per
week, or placebo. Baseline depressive symptoms were
assessed both by the Hamilton Rating Scale for Depres-
sion and a structured interview. Approximately one-half
of the patients had major depression. At 4-month follow-
up, there were comparable reductions in depressive symp-
toms among the patients who received sertraline and
those who underwent exercise, and both groups had
greater reductions in depressive symptoms compared with
placebo. These results are concordant with those of 2
prior randomized studies these investigators performed to
compare exercise with antidepressant medication in non-
cardiac subjects with depression (18,19).
The chief limitation of the present study is its lack of
generalizability. The study population consisted of volun-
teers, who may thus not be typical of depressed patients in
general. The nearly complete compliance with exercise and
prescribed medication in this study is certainly atypical and
suggests that these volunteers were particularly motivated
and less severely depressed than many clinic patients. The
study population was also skewed toward those of higher
socioeconomic status and was ethnically narrow. In addi-
tion, the 3 randomized trials that have now been conducted
by Blumenthal et al. (10,18,19) represent the experience
garnered at only 1 medical center. Thus, there is a need to
perform further multicenter studies that would enroll
broader spectra of patients. It is also notable that the present
study was not an assessment of exercise per se but rather,
supervised group exercise. As such, it is possible that the
social support or the sense of purpose provided by being part
of a group study were important determinants of the
improved mood of the patients assigned to group exercise.
However, in 1 study, Blumenthal et al. (19) found that both
home-based exercise and group exercise served to reduce
depressive symptoms, thus mitigating this concern. Finally,
it is somewhat surprising that exercise was as effective as
sertraline among the subgroup of subjects with severe
depression. This nding, however, is based on a very small
sample size and, given the volunteer status of this popula-
tion, would need to be reproduced in more real-life settings
to assess the applicability of this nding
If further study continues to reproduce these present
ndings, there would be strong clinical appeal for develop-
ing exercise as treatment for depression in cardiac patients.
First, on a practical basis, the use of SSRIs is not without
side effects, which, beyond transient effects involved with
medication initiation, can include sexual dysfunction, a
tendency to polypharmacy in some patients, and a need to
be watchful for drug interactions among patients on multi-
ple cardiac medications. Indeed, in the present study, 25%
of patients randomized to sertraline experienced sexual
dysfunction, and 18% experienced fatigue, while such symp-
toms were rare in the group randomized to group exercise.
Second, in contrast to the current paucity of prognostic
benet associated with SSRI use in cardiac patients, exercise
training is of known prognostic benet among patients with
heart disease. Of interest, a secondary analysis of the
ENRICHD trial found that depressed patients who exer-
cised had a 40% reduction in mortality compared with
depressed patients who did not engage in exercise (20).
Third, the occurrence of acute cardiac events may heighten
not only the risk for depression but also associated fear and
anxiety. Prescribing exercise for such patients may convey a
message of empowerment.
Implementing Exercise as
Medical Treatment for Cardiac Patients
The ndings of Blumenthal et al. (10) raise a practical
question. Overall, current American society is highly sed-
entary and depressed patients even more so. Comorbid
depression and cardiac disease make exercise instruction and
maintenance more complex. Although some depressed pa-
tients may simply respond to their physician instructions
concerning exercise, many will require more assistance than
practicing doctors can provide in constrained medical prac-
tice. In the present study, group exercise for cardiac patients
was freely sponsored through funded research. But in the
real world, there is currently no third-party payer support
for exercise training programs for cardiac patients besides
conventional cardiac rehabilitation, which is relatively
costly, limited in geographic availability, and narrow in its
patient eligibility requirements. Thus, future research
should address the realities of this situation. A practical line
of exploration lies in the medical testing of inexpensive
hospital or community exercise programs that provide either
home-based and/or group-based exercise and adherence
assistance, such as that provided by peer-based and profes-
sional social support, pedometer-based self-monitoring, and
coaching assistance designed to increase patient autonomy,
self-efcacy, and stress management (21). Such exercise
programs can be tested versus conventional medical practice
for their ability to reduce depression and important se-
quelae, such as medication noncompliance, work absentee-
ism, and the high utilization of medical resources that is
associated with depression. The clinical reasons for devel-
oping such exercise programs are already compelling, but
by demonstrating the efcacy of exercise versus antide-
pressant medication for reducing depressive symptoms,
Blumenthal et al. (10) have now provided an important
additional incentive for developing practical exercise
programs for medical patients.
1065 JACC Vol. 60, No. 12, 2012 Rozanski
September 18, 2012:10646 Exercise for Depression in Coronary Disease
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Reprint requests and correspondence: Dr. Alan Rozanski, St.
Lukes and Roosevelt Hospitals, Division of Cardiology, 1111
Amsterdam Avenue, New York, New York 10025. E-mail:
arozanski@chpnet.org.
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Key Words: coronary heart disease y depression y exercise.
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