Depressed and Coping: Treating Depression When Medication Fails

James Russo has wrestled for some 60 years with his "black dog" of depression, since the days back in high school when a B left him feeling like an utter failure. He tried Valium, a tricyclic antidepressant, and Prozac before finding some relief in Paxil. Still, says Russo, 74, of Bernville, Pa.: "My disease lives in the corner of my mind, sometimes sleepy enough to let me enjoy a little optimism but ever ready to ruin a day or a week or a year." What has become abundantly clear in the antidepressant age—the drugs are now the most commonly prescribed medications in the country—is that depression is terribly difficult, if not impossible, to cure. Many primary-care doctors, who treat 80 percent of depressed people, labor under the assumption that a prescription is a panacea. But antidepressants completely alleviate symptoms in only about 35 to 40 percent of people compared with 15 to 20 percent of those who take a placebo—a fact not publicized in pharmaceutical ads. And about 70 percent of people who successfully beat one bout can expect to face another.

Video: Learning About Depression

"We just don't have one magical pill that will do the whole trick," says Madhukar Trivedi, a professor of psychiatry at the University of Texas Southwestern Medical Center in Dallas. He recently participated in the government-funded "Star*D" trial of more than 4,000 patients with difficult-to-treat depression, which showed that success rates of antidepressants could be increased but that it sometimes took four tries of various drugs plus therapy. Even then, in 30 percent of those who completed the yearlong study, symptoms still lingered. And 5 percent of study participants, according to new Star*D data published last week, actually had a worsening of their symptoms while on an antidepressant. In an effort to better combat treatment-resistant depression, the Food and Drug Administration last month approved a combination pill for those who aren't helped by antidepressants alone. The drug, called Symbyax, combines the antidepressant Prozac and the antipsychotic Zyprexa.

Lifestyle culprits. Gradually, though, many mental-health practitioners are coming to believe that adjusting brain chemistry with medication isn't enough—that depression is a complex chronic disease, akin to diabetes, requiring lifestyle changes and ongoing monitoring to address underlying causes. As with diabetes, experts have begun to look for culprits in the 21st-century lifestyle. Might the isolating, sedentary, indoor computer culture explain, for example, why the disorder appears to be surging in young adults? Today's 20-somethings have a 1-in-4 lifetime risk of experiencing depression's hallmark black mood, joylessness, fatigue, and suicidal thoughts compared with the 1-in-10 risk of their grandparents' generation. Americans are 10 times as likely to have depression today as they were 60 years ago, a development that is not merely a result of increased awareness and diagnosis.

There's certainly evidence that vigorous exercise has an effect on mood. Trivedi and others have shown that burning off 350 calories three times a week in sustained, sweat-inducing activity can reduce symptoms of depression about as effectively as antidepressants. Brain-imaging studies indicate that exercise stimulates the growth of neurons in certain brain regions damaged during depression. And animal studies have found that physical exertion increases the production of brain molecules that improve connections between nerve cells and act as a natural antidepressant. Sunlight or light-box exposure often helps people prone to seasonal affective disorder. And there's no doubt that getting a decent night's sleep can lift the spirits. Nutrition may play a role, too: It's fairly well established that those who eat the most fish have the lowest rates of depression.

Realizing that primitive societies like the Kaluli of Papua New Guinea experience virtually no depression, Stephen Ilardi, an associate professor of psychology at the University of Kansas, has been testing a cave-man-esque approach to treatment with promising results. His 14-week Therapeutic Lifestyle Change program entails large doses of simulated hunter-gatherer living in people suffering from prolonged, unremitting depression. Participants sign up for 35 minutes of aerobic exercise (running, walking briskly, biking) three days a week, at least 30 minutes of daily sunlight or exposure from a light box that emits 10,000 lux, eight hours of sleep per night, and a daily fish oil supplement containing 1,000 mg of the fatty acid EPA and 500 mg of the fatty acid DHA.