They are invisible — no bandages or scars — but the mental and physical pain of mood disorders can be unbearable. Anxiety overwhelms the mind with worry, fear and dread. Depression hijacks a person’s sense of well-being, manifesting itself not just in the brain but in an array of physical symptoms — weight loss, stomachaches, headaches. The joy of life is seized and “everything is pretty much flat,” says Robin Goad, 46, who suffers from depression. “It’s real easy to give up.”

      That hopelessness especially grave in people who do not respond to conventional treatments. The psychiatric field has made great strides in recent years: researchers are teasing out the chemical pathways responsible for mood disorders, and new classes of drugs are helping to relieve the agony for millions. Still, the brain is an enormously complex organ, and people’s conditions vary widely. A drug that works wonders for one patient will do nothing for another. And medications come with an array of side effects — jitteriness, drowsiness, sexual dysfunction — that send many people running. As a result, Americans are avidly pursuing alternatives: a telephone survey by Harvard scientists found that about half of those battling depression or anxiety had sought out complementary treatments.
       
     The research is still preliminary and the therapies, from herbs to hypnosis, may never help the most severely afflicted. But as researchers examine the options more closely, the science is beginning to improve. “There are so many people who are suffering,” says Dr. Jerrold Rosenbaum, chief of psychiatry at Massachusetts General Hospital. “The bottom line is, there’s a huge gap between where we are and where we need to be.”

NO BENEFITS?
       
     The market for herbal mood therapies is vast: sales for depression treatments alone rang in close to $60 million in 2001, according to the market-research firm SPINS. St. John’s wort (Latin - Hypericum, German - Johanniskraut), which affects the same brain chemicals targeted by antidepressants — serotonin, noradrenaline and dopamine — became the darling of the bunch over the last few years, boasting symptom relief with few side effects. But so far, results are mixed. The first large-scale trial in the United States, published in April, found no benefit over placebo for major depression of moderate severity in 340 patients. Those findings convinced some that the herb was “dead in the water,” says Dr. Maurizio Fava, head of Mass General’s depression-research program. But even a low dose of the antidepressant Zoloft failed to beat the placebo. A later French study found that St. John’s wort was better than a placebo for mild to moderate major depression. And new data from a still unpublished trial by Fava’s team found that the herb beat a low dose of fluoxetine (generic Prozac).

     Part of the problem is that the herb comes in a variety of formulations that may contribute to contradictory findings. “You never know what you’re getting,” says Dr. Mark Rapaport, a psychiatrist at the University of California, San Diego. Still, the herb is intriguing enough that Rapaport and others are launching a three-site trial to test it against the drug Celexa for minor depression. And even more research is in the works: the Dean Foundation in Madison, Wis., is trying St. John’s wort as a therapy for obsessive-compulsive disorder and social phobias.
       
ENCOURAGING RESEARCH
     
     Perhaps the most natural compound out there is SAMe (S-adenosylmethionine), a molecule produced by our own cells, which appears to boost the activity of dopamine and serotonin. Preliminary research — most of it in Europe, where it has been used for decades — is encouraging. The Department of Health and Human Services recently reviewed 47 studies on SAMe and deemed it better than a placebo and comparable to antidepressants. The compound does have drawbacks: it can cost more than $100 a month. And it should never be used to treat bipolar disorder, because it can induce mania. As with St. John’s wort, more research is needed to determine precisely who might benefit, how much to take and how safe it really is. Dr. Richard Brown, a psychiatrist at Columbia University, has seen promising results and says that for some patients SAMe may be a better option than standard drugs: “It works faster with a lot fewer side effects.”

     Wouldn’t it be great to eat your way out of mood disorders? Researchers have long been intrigued that Asian populations, whose diets are rich in soy and fish, have lower incidences of depression. That may have more to do with stigma and underreporting than daily meals, but the connection is alluring. The National Institutes of Health is now recruiting patients with major depression for an eight-week trial of the soy-based dietary supplement Novasoy. One reason: genistein, an active ingredient in soy, has been found to increase the activity of dopamine and other neurotransmitters in the brain.


DON’T BE SAD: EAT FISH
       
     Foods that contain omega-3 fatty acids, like nuts, flaxseed oil and fatty fish such as salmon and mackerel, have more research backing them up. A 1999 study of bipolar disorder found that patients taking omega-3 fatty-acid capsules as an adjunct to standard therapy were less likely to relapse than patients on drugs alone. In a promising study published last month, researchers reported that patients whose depression was resistant to drugs decreased the severity of symptoms, like sadness, by half when taking omega-3s. Joseph Hibbeln, a senior clinical investigator at the NIH, has found that people in Finland who eat fish twice a week or more cut their risk of depression in half. That may be because fats make up 60 percent of the solid mass of our brains. Omega- 3s “appear to be a fundamental nutrient for optimal brain functioning,” says Hibbeln. A bonus: they protect your heart.
       
     Sometimes the brain itself can adjust the way it functions. Psychotherapy is proof of that: it has been shown to be as effective as antidepressants for mild to moderate depression and can even change brain patterns. But therapy isn’t always available or affordable long term. Dr. David Spiegel, head of Stanford’s Center for Integrative Medicine, is focusing on self-hypnosis in the hopes that patients can think themselves out of negative thought cycles. He’s teaching patients to use self-hypnosis for five minutes, every one to two hours daily. They close their eyes, take a deep breath, imagine they’re floating and then picture a screen, putting what’s depressing them on one side and what they can do about it on the other. Spiegel helped one woman bury the assumption that her boss thought she was incompetent. By imagining herself from the boss’s point of view, then picturing herself working effectively, “she saw herself differently,” says Spiegel. Hypnosis, he says, “is an attempt to shake up the mind-set that depressed people are habitually in.”
       
     Treatments for the body may also help the mind, especially for milder disorders or in combination with other approaches. A pilot study at the University of Arizona found that acupuncture relieved symptoms of major depression in 38 women at rates comparable to psychotherapy or drugs. Interesting, but in no way conclusive. Results from a larger trial of both men and women are expected next year. Columbia’s Brown is teaching psychiatrists an Indian yogic technique through the Art of Living Foundation in New York City, alternating deep breathing with short rapid breaths. A pilot study in India found that half an hour a day of the practice was as effective as the antidepressant imipramine. Is it a first-line treatment? We need more studies. But, like other relaxation methods, it offers another approach—and with no known side effects.
       
LOW ANXIETY
     
     Depression often goes hand in hand with anxiety, so researchers have been looking for ways to damp down the worrying, too. Solid research, however, is sparse. In a recent British study participants taking the herbs valerian and kava in a lab setting reported less stress when performing a word game under pressure. Kava gives people the “near-immediate sensation of relaxation,” says Mark Blumenthal, head of the American Botanical Council. A month-long trial at Duke University found it helped more than a placebo in mild anxiety, but was not as effective in more severe cases. But there’s reason for caution. The compound has been associated with liver problems in Europe, putting a damper on U.S. research — and serving as a reminder that just because a compound is natural doesn’t mean it’s safe.
       
     Other therapies, like yoga and massage, have long been practiced to reduce stress and ease the mind. Exercise helps, too, and has big advantages: no doctors or pharmacies necessary. Duke researchers found that depressed people over 50 who exercised together 30 minutes a day — walking, jogging or biking — three times a week did as well as a cohort taking Zoloft. Six months later, the exercisers had relapse rates of 9 percent, compared with 30 percent among pill takers. James Blumenthal, who led the trials, says social support and the release of endorphins, the brain’s “feel good” neurotransmitters, may contribute to well-being.
     
     Complementary treatments need more research — and they’ll never replace drugs or psychotherapy. But given the wide range in conditions and responses, new options are well worth investigating, especially for people like Robin Goad. After giving up on antidepressants (one worked but left her riddled with side effects), she took St. John’s wort as part of a trial but felt no significant benefits. Now she’s looking for a new therapy and hoping for relief. “You want anything that will make you feel better,” she says. A simple desire for one woman — an ongoing challenge for scientists.

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