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Teens Who Recover from Hard-to-treat Depression Still at Risk for Relapse

Science Update

teen couple embracing

Teens with hard-to-treat depression who reach remission after 24 weeks of treatment are still at a significant risk for relapse, according to long-term, follow-up data from an NIMH-funded study published online ahead of print November 16, 2010, in the Journal of Clinical Psychiatry. The long-term data reiterate the need for aggressive treatment decisions for teens with stubborn depression.


In the Treatment of Resistant Depression in Adolescents (TORDIA) study, teens whose depression had not improved after an initial course of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment were randomly assigned to one of four interventions for 12 weeks:

  • Switch to another SSRI-paroxetine (Paxil), citalopram (Celexa) or fluoxetine (Prozac)
  • Switch to a different SSRI plus cognitive behavioral therapy (CBT), a type of psychotherapy that emphasizes problem-solving and behavior change
  • Switch to venlafaxine (Effexor), a different type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI)
  • Switch to venlafaxine plus CBT

As reported in May 2010, nearly 40 percent of those who completed 24 weeks of treatment achieved remission, regardless of the treatment to which they had initially been assigned. However, those who achieved remission were more likely to have responded to treatment early—during the first 12 weeks.

After 24 weeks of treatment, the participants were discharged from the study and urged to continue care within their community. They were then asked to return for an assessment at 72 weeks.

Results of the Study

Of the 334 original TORDIA participants, about 61 percent had reached remission by week 72. Symptoms of depression steadily decreased after the initial 24 weeks of treatment. But at 72 weeks, many participants still reported having residual symptoms of depression, such as irritability, fatigue and low self-esteem.

Those with more severe depression at baseline were less likely to reach remission. Those who responded early to treatment—within the first six weeks of treatment—were more likely to reach remission. Initial treatment assignment during the study did not appear to influence the remission rate or time to remission.

However, of the 130 participants who had remitted by week 24, 25 percent had relapsed by week 72. Ethnic minorities tended to have a higher risk for relapse than whites.


Because more than one-third of the teens did not recover and the relapse rate was high, the authors conclude that more effective interventions early in the treatment process are needed. In addition, the higher risk of relapse for ethnic minorities suggests that cultural factors may influence the long-term course of depression and recovery, but it is unclear what those factors may be.

What's Next

The findings indicate that new methods are needed to accurately identify those who may not respond early in treatment so that patients unlikely to reach remission using a particular treatment may be offered alternative treatments earlier in the process. More data is needed, however, to be able to predict who might be more likely to remit and who may not.


Vitiello B, Emslie G, Clarke G, Wagner K, Asarnow JR, Keller M, Birmaher B, Ryan N, Kennard B, Mayes T, DeBar L, Lynch F, Dickerson J, Strober M, Suddath R, McCraken JT, Spirito A, Onorato M, Zelazny J, Porta G, Iyengar S, Brent D. Long-term outcome of adolescent depression initially resistant to SSRI treatment. Journal of Clinical Psychiatry. online ahead of print November 16, 2010.