updated 1/2/2006 10:52:16 AM ET 2006-01-02T15:52:16

A third of people suffering serious depression recover with the first antidepressant they try, and well-educated white women are most likely to benefit, according to initial results of an eagerly awaited study on the controversial drugs.

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One key finding: Patients whose depression symptoms disappeared took higher than typical drug doses, and received close monitoring and frequent dose adjustments in the first three months — a level of care that few U.S. patients today receive.

Stay tuned.

The main goal of the government-funded study is to identify what harder-to-treat patients should try when initial treatment fails, instead of abandoning therapy in frustration. Those results are due in a few months.

Psychiatrists have long known that for most depression sufferers, the first antidepressant choice won't be a panacea, just as patients with epilepsy, heart disease or cancer often must mix and match medications before finding the best choice.

But unlike those illnesses, physicians have had little scientific evidence until now to guide their choices of myriad antidepressants — or how to maximize each patient's chances of benefit.

To do that, "tailor the treatment," stressed Dr. Madhukar Trivedi of the University of Texas Southwestern Medical Center, who reported first results from the study Sunday in The American Journal of Psychiatry.

How? The study created an easy-to-use rating system to quickly assess depression symptoms and report drug side effects. That rating system — now posted on a Web site for any doctor to use — allowed patients' drug doses to be adjusted every two to three weeks until they hit the right balance, or it became clear that some other therapy was needed.

It's rare today that antidepressant users receive this so-called measurement-based care, said Dr. Richard Nakamura, deputy director of the National Institute of Mental Health, which funded the $35 million study.

"Many people, because they're not given followup, the medications aren't adjusted ... do end up being frustrated, and any negative side effects, any trouble with dosage levels, will cause them to end treatment," Nakamura said.

A bonus: The ratings led to closer physician monitoring, with five to six visits during the critical first months of antidepressant use.

Controversial drugs
Antidepressants have proved extremely controversial in recent years because of evidence that they on rare occasions worsen suicidal tendencies in children or teenagers. In 2004, the Food and Drug Administration ordered strong warnings about the pediatric risk be put on antidepressant labels, and began analyzing whether adults face a similar risk.

Meanwhile, FDA urges that antidepressant users of all ages be closely watched for agitation of other symptoms that might signal suicidal behavior during the first weeks of therapy.

There were no suicides among the almost 3,000 patients in Trivedi's study, known as STAR-D.

A separate study also published in the psychiatry journal tracked more than 65,000 people — mostly adults — who used antidepressants in a 10-year period and were insured by the Seattle-based Group Health Cooperative. The risk of a serious suicide attempt actually was highest in the month before patients started antidepressants, and the risk of a serious attempt or a completed suicide dropped in the weeks after treatment began, the Cooperative researchers, also funded by NIMH, concluded.

"This study lends us some very important information" about adults, but "it doesn't, however, alter our ongoing concern about children," cautioned Dr. Paul Seligman, who heads FDA's Office of Drug Safety.

Ten percent of men and a quarter of women will suffer from depression some time in their lives, and it often recurs. There are about 20 medications and a variety of talk-based therapies, but little evidence to say who is most likely to benefit from which approach.

Until now, most research has consisted of industry-funded comparisons of a single drug with a placebo, among patients not considered particularly difficult to treat.

The six-year STAR-D study aims to fill that gap.

In step 1, all enrolled patients were given Celexa, part of a newer class of antidepressants known as selective serotonin reuptake inhibitors, or SSRIs.

The researchers aren't endorsing Celexa, Trivedi stressed. The odds of benefit should be similar with any first-choice SSRI. Celexa was chosen for research-oriented reasons, including once-daily dosing.

Researchers can't explain why white women, especially the well-educated, were most likely to recover with initial treatment. Also more likely to benefit were patients with fewer co-existing illnesses and less severe depression.

Those who didn't become symptom-free were moved to step 2, assigned a variety of different therapies to determine care for harder-to-treat patients.

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