Dr. Carney calls this "the Holy Grail of behavioral psychology." He believes this goal has proved elusive to date because the standard antidepressant therapies, whether pharmacologic or psychotherapies, are "fairly modest" in their effects, and depression is often a remitting and relapsing disorder.
He noted that an analysis of clinical trials data on close to 7,000 patients that was submitted to the Food and Drug Administration on behalf of six widely prescribed antidepressants concluded that the medications were overall just 2 points better on the 17-item, 50-point HAM-D than placebo (Prevention & Treatment 2002;5: article 23). That’s not very impressive. And a recent meta-analysis of five randomized trials comparing exercise training to a control condition in treating patients with major depression concluded that exercise was a mean of only 2.4 HAM-D points better (J. Clin. Psychiatry 2011;72:529-38).
"Exercise appears to be doing about as well as antidepressant drugs or some of the psychotherapies, but it’s not doing a whole lot better," Dr. Carney asserted. "It seems clear to me that monotherapy for depression is often insufficient, both in psychiatric patients and in CHD."
There is, however, some intriguing evidence to suggest that exercise training might be particularly effective in patients whose depression doesn’t respond to traditional antidepressant therapies, the psychologist said. For example, Scottish investigators took 86 primary care patients with major depressive disorder unresponsive to at least 6 weeks of an adequately dosed antidepressant drug and randomized them to a combined endurance and weight-training exercise program or a group health education control group. The two groups met twice weekly for 10 weeks, at which point at least a 30% improvement in HAM-D scores had occurred in 55% of the exercise group, compared to 33% of controls (Br. J. Psychiatry 2002;180:411-5).
For this reason, Dr. Carney proposed that when planning gets underway for the next large, multicenter clinical trial testing the hypothesis that treating depression in CHD patients improves survival, an exercise-training arm should be incorporated. But not exercise as monotherapy; instead, exercise should be employed as part of a combination treatment or augmentation strategy, or perhaps in a sequential stepped-care regimen for initial nonresponders.
"If we could improve on [the low rates of cardiac rehab utilization], that alone would be doing a huge public health service." -- Dr. Davidson
This stepped-care approach proved highly effective in the landmark, randomized, multicenter Sequential Treatment Alternatives to Relieve Depression (STAR*D) trial. In step 1 of STAR*D, the remission rate with antidepressant monotherapy was 33%; in step 2, with the addition of a second antidepressant or a switch to a different one, the cumulative remission rate climbed to 53% (Am. J. Psychiatry 2006;163:1905-17).
Exercise training as part of combination antidepressant therapy in patients with CHD is attractive for several reasons. Not only may it be more effective than monotherapy, but it confers numerous cardiovascular and general health benefits. And it avoids drug-drug interactions.
"I think that’s a really important consideration in cardiac patients, who often are on 8, 10, or 12 different drugs. And SSRIs in particular seem to interact with other drugs," Dr. Carney said.
Dr. Blumenthal commented that he, too, is very interested in pursuing a STAR*D-type approach in clinical trials of antidepressant therapy in patients with CHD.
"I think combining exercise and cognitive behavioral therapy could potentially be very effective. We’re now looking at this in a small study at Duke," the psychologist said.
But he thinks that before exercise training for depression in CHD patients gets put to the test in a definitive multi-thousand-patient, National Institutes of Health–sponsored randomized trial, the groundwork needs to be carefully laid in a series of smaller, 150- to 200-patient trials that provide guidance as to how best to utilize the therapy.
Karina W. Davidson, Ph.D., commented that she found "just astounding" Dr. Lavie’s account of the low rates of cardiac rehab utilization in CHD patients.
"Those of us in the Society of Behavioral Medicine should be thinking scientifically about how we can lift those barriers. Where are the holes in the pipeline? What can you be doing to test if you are correct in your conceptualization and theory of why people aren’t making it to cardiac rehab? If we could improve on those numbers, that alone would be doing a huge public health service," said Dr. Davidson, professor of medicine and psychiatry at Columbia University, New York.
She also would like to see lots more cost-effectiveness analyses from behavioral scientists working in the field of antidepressant therapy for CHD patients. In this regard, she was particularly intrigued by Dr. Blumenthal’s finding in SMILE II that a home-based individual exercise training program was as effective as the standard, considerably costlier group class format.