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Early Treatment Decisions Crucial for Teens with Treatment-resistant Depression

Science Update

two young men sitting on bleachers talking

An early response to second-course treatment is associated with greater likelihood of remission among teens with hard-to-treat depression, according to recent data from an NIMH-funded study published online ahead of print May 17, 2010, in the American Journal of Psychiatry.

"These results suggest that early treatment decisions are probably the most crucial to the recovery of teens with hard-to-treat depression," said NIMH Director Thomas R. Insel, M.D.

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), another type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI)
  • Switch to venlafaxine plus CBT

As reported in February 2008, after 12 weeks, about 55 percent of those who switched to either type of medication and added CBT responded, while 41 percent of those who switched to another medication alone responded.

For the most recent findings, Graham Emslie, M.D., of the University of Texas Southwestern Medical Center at Dallas, and colleagues measured the teens' rate of remission after 24 weeks of treatment. Among the 334 TORDIA participants, 78 percent completed the 24-week assessment. The researchers found that nearly 40 percent of those who completed 24 weeks of treatment achieved remission, regardless of which 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.

Those who had very severe depression at baseline, a sense of hopelessness, anxiety and family conflict were less likely to achieve remission. Those who were taking an additional mood stabilizing medication, such as an antipsychotic or anti-anxiety medication, or who were receiving CBT, were more likely to achieve remission, but ONLY if the teens received these additional treatments in the first 12 weeks.

Moreover, those who achieved remission tended to have responded to treatment by six weeks into treatment compared to those who had not achieved remission by 24 weeks, underscoring the importance of early treatment decisions.

The authors suggest that the current clinical guidelines, which recommend staying with a treatment for at least eight to twelve weeks before trying another, may need to be revisited. More research is needed to clarify when is the optimal time to change a treatment strategy among treatment-resistant teens with depression, they concluded.


Emslie GJ, Mayes T, Porta G, Vitiello B, Clarke G, Wagner KD,Asarnow JR, Spirito A, Birmaher B, Ryan N, Kennard B, DeBar L, McCracken J, Strober M, Onorato M, Zalazny J, Keller M, Iyengar S, Brent D. Treatment of resistant depression in adolescents (TORDIA): week 24 outcomes . American Journal of Psychiatry. Online ahead of print May 17, 2010.