Is Exercise the Best Drug for Depression?

At his research clinic in Dallas, psychologist Jasper Smits is working on an unorthodox treatment for anxiety and mood disorders, including depression. It is not yet widely accepted, but his treatment is free and has no side effects. Compare that with antidepressant drugs, which cost Americans $10 billion each year and have many common side effects: sleep disturbances, nausea, tremors, changes in body weight.

This intriguing new treatment? It's nothing more than exercise. (See how to handle illness at any age.)

That physical activity is crucial to good health — both mental and physical — is nothing new. As early as the 1970s and '80s, observational studies showed that Americans who exercised were not only less likely to be depressed than those who did not but also less likely to become depressed in the future. (See the Year in Health for 2009 from A to Z.)

In 1999, Duke University researchers demonstrated in a randomized controlled trial that depressed adults who participated in an aerobic-exercise plan improved as much as those treated with sertraline, the drug that, marketed as Zoloft, was earning Pfizer more than $3 billion annually before its patent expired in 2006.

Subsequent trials have repeated these results, showing again and again that patients who follow aerobic-exercise regimens see improvement in their depression comparable to that of those treated with medication, and that both groups do better than patients given only a placebo. But exercise trials on the whole have been small, and most have run for only a few weeks; some are plagued by methodological problems. Still, despite limited data, the trials all seem to point in the same direction: exercise boosts mood. It not only relieves depressive symptoms but also appears to prevent them from recurring. (See the top 10 medical breakthroughs of 2009.)

"I was really surprised that more people weren't working in this area when I got into it," says Smits, an associate professor of psychology at Southern Methodist University.

Molecular biologists and neurologists have begun to show that exercise may alter brain chemistry in much the same way that antidepressant drugs do — regulating the key neurotransmitters serotonin and norepinephrine. At the University of Georgia, neuroscience professor Philip Holmes and his colleagues have shown that over the course of several weeks, exercise can switch on certain genes that increase the brain's level of galanin, a peptide neurotransmitter that appears to tone down the body's stress response by regulating another brain chemical, norepinephrine.

The result is that exercise primes the brain to show less stress in response to new stimuli. In the case of lab rats and mice, those stimuli include being plunged into very cold water or being suspended by the tail. And while those are not exactly problems most people face, the thinking is that the human neurochemical response may well react similarly, with exercise leaving our brain less susceptible to stress in the face of harmless but unexpected events, like missing an appointment or getting a parking ticket. A little bit of mental strain and excess stimulation from exercise, in other words, may help us to keep day-to-day problems in perspective.

Researchers wonder whether this interaction between body and brain may, evolutionarily speaking, be hardwired. "It occurs to us that exercise is the more normal or natural condition and that being sedentary is really the abnormal situation," Holmes says.

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