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David Baxter PhD

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Change in Antidepressants May Beat Depression
March 23, 2006
By Amanda Gardner, HealthDay

About half of people battling depression can achieve complete remission by either adding one more drug to their regimen, or switching to a new medication, a major new trial finds.

"Remission can be achieved in 50 percent of those who receive two treatment steps," said Dr. John Rush, principal investigator of the study and professor of psychiatry at the University of Texas (UT) Southwestern Medical Center in Dallas. "Thus, for patients, it's important to not give up if the first treatment doesn't work fully, or if it causes side effects."

"Treatment does work for most people if it's delivered in an adequate dose and over an appropriate period of time, meaning 12 weeks," added Dr. Thomas Insel, director of the National Institute of Mental Health, which funded the trial. "For someone who's not well at 12 weeks, another medication can bring remission. That's an extremely important and hopeful message. One size doesn't fit all."

Both Rush and Insel spoke at a teleconference Monday to announce the latest results of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest effectiveness study ever done on depression, and one which examined the benefits of antidepressants in "real world" settings. The results are also published in two papers in the March 23 issue of the New England Journal of Medicine.

Depression is a chronic, disabling condition affecting some 15 million Americans -- almost 7 percent of the adult U.S. population, Insel said. Some 4 percent of people with depression will end their own lives, resulting in 30,000 suicides each year. "That's almost twice the number of homicides," Insel pointed out. "It's a very real public health challenge."

Unfortunately, about half of people with depression don't receive treatment and, of those who do get treatment, only about 40 percent get the best, "evidence-based" treatment. Some people still don't get better even with this type of treatment, however.

Antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) -- which include drugs such as Celexa, Paxil, Prozac and Zoloft -- are considered among the most effective treatments available for depression. However, doctors haven't had good evidence on the best course of action to take if and when a patient fails to respond to a particular SSRI.

The STAR*D trial was designed to answer that question. Importantly, the trial looked at remission, meaning full recovery, as opposed to "response," which means partial relief of symptoms. Participants, all of whom had nonpsychotic major-depressive disorder, were being treated in real-world settings. Unlike many clinical trials, many of the STAR*D participants also had coexisting psychiatric and/or medical conditions, or were unemployed or lacked health insurance.

For the first part of the study, more than 700 adults who had failed Celexa (citalopram) or who could not tolerate the drug were randomly assigned to receive, instead, one of three drugs for up to 14 weeks: sustained-release Wellbutrin (bupropion, not an SSRI), Zoloft or Effexor (venlafaxine, an SSRI-SNRI).

About a quarter of the participants achieved total remission, regardless of the particular drug used.

"Three different 'switch' medications were tested," Rush said. "No one was clearly better than another, even though these treatments do differ in how they work in the brain. Which treatment may be less important than the drugs being used diligently and effectively."

Importantly, the study showed that the current standard of four weeks of therapy is often not enough to see a benefit. "This suggests that longer treatment would be beneficial," Rush said.

The second study looked at the value of adding Celexa (citalopram) to either Wellbutrin or Buspar (buspirone) in 565 adult outpatients treated for depression.

"One in three got into remission with the addition of another medication," Rush said. "Again, despite differences in how the drugs work, both worked with about the same degree of efficacy [people on Wellbutrin did slightly better] and tolerability, and therefore both are reasonable choices for patients who have not gotten fully well with the first treatment step."

However, about 50 percent of patients did not achieve full remission with the strategies used, a statistic that an accompanying editorial called "discouraging."

The authors, however, defended the results.

"In this kind of real-world, chronic medical illness, two steps produced full recovery in over 50 percent of patients," said Dr. Madhukar H. Trivedi, co-principal investigator of the trial and professor of psychiatry at UT Southwestern Medical Center, Dallas. "When you compare that to most major medical illness, they are actually very encouraging results."

"It's a multi-center trial taking place around the country and they really tried to take a variety of patients who would be representative of the real world, and that is so important," added Dr. Eva Ritvo, an associate professor of psychiatry at Miller School of Medicine of the University of Miami. "It's real-world data with big numbers, which are so hard to get. There's a tremendous amount of value in the study."

In the meantime, the patients who did not respond to even a second-tier treatment are being followed to see if other treatments are effective. That data is not yet available.

"This is by no means the end game," said Dr. Maurizio Fava, director of the Massachusetts General Hospital's Depression Clinical and Research Program in Boston. "In the near future, we may be able to predict who is going to respond to what."
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