Approximately half of the people battling depression can achieve complete remission by either adding one more drug to their regimen or by switching to a new medication, according to researchers.

Selective serotonin reuptake inhibitor (SSRIs), which include citalopram (Celexa), paroxetine (Paxil), fluoxetine (Prozac) and sertraline (Zoloft)-are considered effective medications to treat depression. However doctors have not had good evidence on the best course of action if a patient fails to respond to a particular SSRI.

The Trial-Part 1

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest effectiveness study ever done on depression, examined the benefits of antidepressants in "real world" settings.

The trial looked at rates of remission (full recovery)-as opposed to response (partial relief of symptom)-in people who had nonpsychotic major-depressive disorder. Unlike many other clinical trials, most 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 not responded to Celexa or who could not tolerate this drug were randomly assigned to receive instead either sustained release bupropion (Wellbutrin, not an SSRI), Zoloft or venlafaxine (Effexor, not an SSRI) for up to 14 weeks.

Approximately 25% of the participants in the trial achieved total remission, regardless of the drug used.

"Three different 'switch' medications were tested," says Dr. A. John Rush, principal investigator of the study and professor of psychiatry at the University of Texas (UT) Southwestern Medical Center in Dallas. "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."

The study also indicated that four weeks of drug therapy, the amount of time doctors believe is necessary before improvements are noticed, is often not long enough to see a benefit, Rush says.

The Trial-Part 2

The second part of the study looked at the value of adding Celexa to the drug regimens of 565 adult outpatients who were taking either Wellbutrin or Buspar (buspirone) for depression.

"One in three patients went into remission with the addition of another medication," Rush says. 'Again, despite differences in how the drugs work, both worked with approximately the same degree of efficacy and tolerability, and therefore, both are reasonable choices for patients who have not gotten fully well with the first treatment step."

Patients who did not respond to a second-tier treatment are being followed-up to see if other treatments are effective.


"Remission can be achieved in 500/o of those who receive two treatment steps," Rush concludes. "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," adds 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."

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

Dr. Eva Ritvo, an associate professor of psychiatry at the Miller School of Medicine at the University of Miami, agrees. "It's real-world data with big numbers, which are so hard to get. There's tremendous value in the study," she notes.

"This is by no means the end game," explains 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."

Depression is a chronic, disabling condition affecting approximately 15 million Americans -almost 7% of the adult population in the United States, Insel says. Approximately 4% of the people who have depression will end their own lives, resulting in 30,000 suicides each year. "That's almost twice the number of homicides," Insel points out. "It's a very real public health challenge."

In addition, approximately half of the people who experience depression don't receive treatment, and of those who do get treatment, only approximately 400/o receive the best, "evidence based" treatment.

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