As many as 97% of all adolescents who are diagnosed as having major depressive disorder recover within 4 years, but nearly half of them have a recurrence during that time, according to a report published online Nov. 1 in the Archives of General Psychiatry.
As expected, those who respond well to short-term treatment are more likely to recover. Surprisingly, however, full responders to short-term treatment are no less likely to develop a recurrence than are partial or nonresponders, said John Curry, Ph.D., of the child and family study center at Duke University, Durham, N.C., and his associates.
The investigators sought to characterize both recovery from and recurrences of major depression among adolescents. They performed an extended, 5-year follow-up of 196 subjects who had participated in TADS (Treatment for Adolescents With Depression Study), an 18-week trial that compared responses to fluoxetine, cognitive-behavioral therapy, a combination of the two, and placebo.
The researchers described this as "the largest treatment follow-up sample of depressed adolescents to date."
Approximately 97% of the study subjects recovered from their index episode of major depression. A total of 30% recovered at 6 months, 66% at 12 months, 85% at 18 months, 88% at 24 months, 92% at 30 months, 95% at 36 months, and 97% at 42 months.
As Dr. Curry and his colleagues had hypothesized, recovery at 2 years was significantly more likely to occur among adolescents who had fully responded to short-term treatment (96% recovery rate) than among those who had shown only a partial response or no response in the short term (79% recovery rate). Also as expected, recovery at 2 years was associated with less-severe depression, absence of sleep, or appetite disturbance, as well as better functioning during the depressive episode.
Of the 189 patients who recovered, 101 (53%) remained well throughout 5 years of follow-up, whereas 88 (47%) had a recurrence. Most of these patients had only a single recurrence, but 12 patients had two recurrences and 2 patients had three recurrences during that time. The cumulative recurrence rates were approximately 2% at 1 year post diagnosis, 12% at 2 years, 30% at 3 years, and 38% at 4 years, the investigators said (Arch. Gen. Psychiatry 2010 Nov. 1 [doi:10.1001/archgenpsychiatry.2010.150]).
The mean interval between recovery and onset of a first recurrence was 22 months.
Contrary to expectations, the recurrence rate among full responders (54%) was not lower than that among nonresponders or partial responders (46%). Also unexpected was the finding that patients who received the optimal therapy from the start – fluoxetine plus CBT – had a recurrence rate (49%) that was not significantly different from that of patients who had first been treated with less-than-optimal therapy or even placebo (46%).
Female sex proved to be the most robust predictor of recurrence. "To our knowledge, this is the first study documenting higher recurrence rates among treated adolescent females," the investigators noted.
In the literature, there is no sex difference in recurrence among adults; a community-based study did show such a difference but only in patients aged 19-23 years. "This age range overlaps ours, suggesting that female vulnerability to recurrence may be age-related." Hormonal factors, low perceived mastery, or a ruminative response style characteristic of females in this age group might be responsible, Dr. Curry and his associates said.
Another possible contributor to this sex difference may be related to anxiety. Concomitant anxiety disorder is a predictor of recurrence, and such disorders were more common among females (28%) than among males (15%) in this study.
The investigators also looked at the emergence of bipolar disorder among this population and found this to be a relatively rare occurrence. In all, 9 females and 3 males (6% of the study subjects overall) were diagnosed as having bipolar disorder during follow-up, and 9 of these 12 had not responded to short-term treatment. Bipolar disorder tended to emerge at the end of follow-up, when subjects were a mean age of 18 years old.
The investigators said the most significant limitation of their study was that slightly fewer than half of the TADS participants took part. "This likely reflects the difficulty of maintaining a sample of adolescents during a period when many are moving away from home," they wrote.
This study was funded by the National Institute of Mental Health. Dr. Curry disclosed ties to the REACH Institute, an organization dedicated to quickly disseminating the latest scientific findings on the mental health of children to professionals and families. His associates disclosed ties to numerous pharmaceutical companies.