The largest trial of its kind, STAR*D (Sequenced Treatment Alternatives to Relieve Depression) followed 3,671 patients, most of whom had suffered from depression for years, as they tried a sequence of treatments that were closely supervised by their own doctors. "Unlike previous studies that had strict inclusion criteria, the focus of our research now is on real-world practices so that the results will be of practical use," says Thomas Insel, MD, director of the National Institute of Mental Health, which sponsored the study. Participants were first put on the antidepressant Celexa for 12 to 14 weeks. Those whose symptoms cleared up or improved significantly entered a yearlong follow-up phase. Others had three options: switching to a new drug (Wellbutrin, Effexor, or Zoloft), remaining on Celexa and adding another drug (Wellbutrin or BusPar) or cognitive therapy, or trying the therapy alone. The third and fourth phases let patients try other antidepressants, such as Pamelor or Remeron.

The results: One-third of depressed patients, the study indicates, will not get better—symptom free—even with up to four treatment attempts. About two-thirds will (37 percent did by just taking Celexa). At the same time, however, the more options they tried, the more likely they were to relapse, with 34 percent of those helped by Celexa alone showing symptoms again within a year, and half of those who tried four treatments falling back into depression.

"The good news is, if a first treatment doesn't work, you should not give up, because a second, third, or fourth might," says Madhukar Trivedi, MD, a professor of psychiatry at the University of Texas Southwestern and one of the lead researchers. Even drugs in the same class may have different effects, says Helen Mayberg, MD, a professor of psychiatry and neurology at Emory University in Atlanta.

For patients who don't respond to any drugs, the experts say that one clear choice is cognitive therapy. "Research has found that it can increase one's chances of staying well long-term," says Mayberg. In more extreme cases, electroconvulsive therapy or vagus nerve stimulation (in which a small pacemaker-like device is implanted in the chest to stimulate nerves that send impulses to affect mood centers in the brain) may be worth trying.

"No one in this field is satisfied with the status quo," says Mayberg. "We know we need better treatments. But we still have to identify the brain patterns and genetic markers that will help us get there. Luckily, we have the tools to do that now, and science is beginning to catch up."
As a reminder, always consult your doctor for medical advice and treatment before starting any program.


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