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Humans (and lab rats) never evolved to be cooped up, still, all day long. Our brains simply may not be built for an environment without physical activity. Research has also suggested that exercise may be an effective treatment for not just depression but also related anxiety disorders and even substance dependence.
Other scientists have found that in mammals, exercise also boosts the production of brain-derived neurotrophic factor (BDNF), a substance that supports the growth and maintenance of brain cells. In depressed patients, BDNF has been shown to help repair brain atrophy, which can lift symptoms of the disease.
Smits says his exercise treatment appeals to patients for two main reasons. First, exercise doesn't carry the same stigma among patients (and some providers) that depression medication and psychotherapy do. Second, the mood-enhancing benefits of exercise can kick in fast — a lot faster than, say, its impact on weight loss or cardiovascular health. "By and large, for most people, when they exercise 30 minutes — particularly when it's a little bit more demanding and they get their heart rate up — they feel better," Smits says. "You get an immediate mood lift."
That effect doesn't reflect the longer-term changes in the brain that Holmes studies. But Smits uses the immediate mood boost as a way to motivate patients with depression (which, of course, manifests in a chronic lack of motivation) to get moving. Instead of a barrier to exercise, Smits suggests, depression can become a reason to exercise. "You feel crappy, so you get on the treadmill, and you look back and you say, 'Wow, I feel much better,' " he says.
Yet for all the potential clinical benefits, the big questions about exercise treatment remain unanswered: How much? How long? In which patients? In their recent book for therapists, Exercise for Mood and Anxiety Disorders (Oxford University Press, 2009), Smits and co-author Michael Otto at Boston University suggest precise exercise doses that they hope will aid psychologists and primary-care doctors in prescribing exercise as treatment — which can be administered in combination with other treatments, of course.
Smits and Otto recommend the familiar 30 minutes of moderate-intensity aerobic exercise, like walking, five times per week, or 30 minutes of high-intensity aerobic exercise three times a week. These doses, which are regularly recommended for physical fitness, are the only ones that have been well tested for depression. "But we can't say at this point that more wouldn't be better," Smits says. "Or maybe less would be better. We really don't know." Too few tests have been run. It is also unclear whether anaerobic exercise, like weight lifting, would have the same mood-lifting effects, or whether exercise works as well in severely depressed patients as it does in sufferers of mild to moderate depression.
For now, then, data on exercise are only suggestive. The clinical literature on antidepressant drugs is massive, since large-scale, rigorous studies are required for market approval from the FDA. The trials on exercise have all been smaller, perhaps in part because they need no government approval. "If you look at FDA standards [for evidence], it's not clear that exercise would meet that standard," says James Blumenthal, the Duke University professor of medical psychology who ran Duke's 1999 exercise study as well as a 2007 follow-up with more than 200 patients, which Blumenthal believes is the largest such trial to date.
But the evidence is mounting, and it's hard to argue with a free treatment that is exempt from side effects for a pervasive and debilitating mental-health scourge — especially when so many other health benefits of exercise are incontrovertible. "I think that we have reason to be optimistic," Blumenthal says. "For people who at least want to consider exercise as a possible treatment, and for whom exercise is safe, it's definitely worth a shot."