Study Aimed at Treating Drug-Resistant Depression

Only about one-third of people with major depression respond to the most commonly used antidepressants. The National Institute of Mental Health has funded a multimillion-dollar study to figure out how to help people who don't respond to treatment.


Every year about 15 million Americans suffer one or more episodes of clinical depression. Two studies in the New England Journal of Medicine test ways to help people who don't respond to drug treatment. NPR's Joanne Silberner reports that the best thing to do is to keep trying.


The new studies stem from a basic problem of psychiatry. The major tools for treating depression are various drugs, and they don't work all that well. Thomas Insel heads the National Institute of Mental Health.

Dr. THOMAS R. INSEL (Director, National Institute of Mental Health): We know that in a 12-week trial with an adequate dose of an antidepressant about a third get well. That leaves two thirds still needing another treatment.

SILBERNER: But there's been no standard of what to do next. There are a lot of choices. Antidepressants that affect different chemicals in the brain. Some affect serotonin, some affect dopamine, some epinephrine. They had to limit what drugs they tested, so both studies used only people who didn't get better when they took a selective serotonin reactive inhibitor, or SSRI, called Citalopram or Celexa. In the first study, 700 people were switched from Citalopram to one of three other drugs known by their brand names Wellbutrin, Zoloft and Effexor. In the second study, 600 people were left on Citalopram while they also took one of two other drugs known by the brand name Wellbutrin and Buspar. John Rush of the University of Texas Southwestern Medical Center headed the analysis of the first study.

Dr. JOHN RUSH (University of Texas Southwestern Medical Center): The study results show that one in four of these patients achieved remission by switching to another antidepressant medication.

SILBERNER: Rush said they've had some success with all three drugs they tried.

Dr. RUSH: No one medication was clearly better than another, even though these treatments do differ in how we believe they work in the brain. They have different pharmacologic effects.

SILBERNER: In the second study, researchers tried adding Buspar or Wellbutrin to the Citalopram. In that study, one in three recovered from previously untreatable depression. Thomas Insul of the National Institute of Mental Health says the findings ought to give confidence to clinicians to keep trying. That switching drugs or adding drugs can help a significant number of people. He says researchers are going to have to keep trying, too.

Dr. INSUL: The glass is half full from our perspective. We've got something here that needs to be used better because it can really make a difference for people with a very serious illness. The glass is half empty in the sense that we need to come up with yet better treatments in the future that increase remission to a hundred percent, well beyond what it is now. And also do this much more quickly than acquiring 12, or in some case, maybe 24 weeks before one sees the remission that is being reported in these studies.

SILBERNER: The NIMH is sponsoring several studies that might take the trial and error out of this completely by using genetic tests that will predict which drug will work best for each individual. Meanwhile, psychiatrist Gregory Simon of Group Health Cooperative in Seattle says the studies might have some implications for prescription drug insurance. Given that some antidepressants cost dollars a dose, and some cost pennies.

Dr. GREGORY SIMON (Psychiatrist): With that information, it's reasonable for an insurance company to say if you're starting with the first medicine, you should use one of the less expensive ones. If you're switching to a second medicine, you should also use one of the less expensive ones.

SILBERNER: A thought that may not go over well with some doctors who would prefer more independence in their prescribing. The current studies have generated some debate within the psychiatric community. For one, the drugs weren't tested against no drugs at all. The researchers say that's because they would've had a hard time finding people with major depression willing to forego medication. And the current studies didn't include cognitive behavioral therapy or other talk therapy that's been shown to augment the effects of drugs. That study, in fact, has been done. Researchers are hoping to publish the results this fall. Joanne Silberner, NPR News.

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