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A study of adolescents who had a major depressive disorder found that nearly all recovered from their episode after treatment. But within five years, nearly half of them had relapsed, and females were at much higher risk of another major episode, researchers at Duke University Medical Center found.

"We need to learn why females in this age range have higher chances of descending into another major depression after they have made a recovery," said John Curry, PhD, lead author of the study and professor in the Duke Department of Psychiatry and Behavioral Sciences.

The study was published in the Nov. 1 issue of the Archives of General Psychiatry.

The current study was a follow-up investigation of 86 male and 110 female adolescents who had participated in the Treatment for Adolescents with Depression Study (TADS), a short-term depression treatment study of 12 weeks.

Major depression is a mood disorder characterized by depressed mood; loss of interest, disruptions in appetite, sleep, energy; poor concentration; worthlessness; and suicidal thoughts or behavior. Adolescents must have at least five of these symptoms for a length of time to be diagnosed with major depression.

In TADS, the adolescents were all at least moderately to severely depressed and the average length of time they had been depressed before they started treatment was about 40 weeks. The depression had also interfered with their school work, family life, or their friendships.

After the initial 12-week treatment, the subjects were then followed for five years by the current study, known as SOFTAD (Survey of Outcomes Following Treatment for Adolescent Depression).

The followup study found that 96.4 percent of the participants had recovered for at least eight weeks after short-term treatment. Those who responded to the short-term treatment rather than partially or not at all were significantly more likely to recover by the two-year follow-up mark.

The most effective treatment was a combination of the antidepressant fluoxetine (Prozac) with cognitive behavioral therapy.

Reaching recovery within two years was not significantly related to being in the group that received the combination therapy. Instead, it mattered whether the patients responded to treatment, no matter what the treatment, as opposed to being partial responders or nonresponders.

The three other arms of the short-term treatment were fluoxetine alone, cognitive therapy alone, or a placebo. (After the short-term treatment, those who had been in the placebo group were offered their TADS treatment of choice).

Of the 189 patients who recovered (out of the total of 196), 88 of them, or nearly half, had a recurrence of major depression. Recurrence couldn't be predicted by the child's full short-term treatment response or by original treatment. Those who responded fully or partially were less likely to have a recurrence than were nonresponders, 42.9 percent versus 67.6 percent, respectively.

Gender played a significant role in recurrence, with a majority of females (57.6 percent) having another major depression versus just 32.9 percent of males.

Curry hypothesized that females may tend toward depression recurrence for a variety of reasons.

Young females may be at risk for a second depression if they have a feeling that they cannot personally make any impact, which affects the desire to set or reach goals, or if they have a tendency toward unproductive, repetitive thoughts that focus on their negative experiences, personal weaknesses, or bad feelings, he said.

Although females are more likely to become depressed than males during adulthood as well as adolescence, adult women are not more likely than men to have a second major depression, Curry said.

"Further research needs to be done to confirm our findings and to sort out the variables that may be associated with recurrent major depression in young women," Curry said.

The study was funded by the National Institute of Mental Health.

Senior author was John March, MD, MPH, professor of child and adolescent psychiatry at Duke and director of Neurosciences Medicine for the Duke Clinical Research Institute.

Other Duke authors include Susan Silva, Barbara Burns and Karen Wells of the Department of Psychiatry and Behavioral Sciences, and from the Duke Clinical Research Institute, Dr. Silva and Jerry Kirchner. Many other authors from other institutions contributed to this study.

Dr. Curry and Dr. Wells provide training through the REACH Institute. Dr. March owns equity in MedAvante; is a consultant for Pfizer, Wyeth, Bristol-Myers Squibb, and Johnson & Johnson; is an advisor for Lilly (maker of Prozac), Pfizer, Scion, and Psymetrix; receives research support from Pfizer and Lilly; and receives royalties from MultiHealth Systems, Guilford Press, and Oxford University Press.