Skip to main content

Transforming the understanding
and treatment of mental illnesses.

Celebrating 75 Years! Learn More >>

 Archived Content

The National Institute of Mental Health archives materials that are over 4 years old and no longer being updated. The content on this page is provided for historical reference purposes only and may not reflect current knowledge or information.

Getting Closer to Personalized Treatment for Teens with Treatment-resistant Depression

Science Update

teenage boy in front of brick wall

Some teens with treatment-resistant depression are more likely than others to get well during a second treatment attempt of combination therapy, but various factors can hamper their recovery, according to an NIMH-funded study published online ahead of print February 4, 2009, in the Journal of the American Academy of Child and Adolescent Psychiatry.


About 40 percent of teens with major depression do not get well after a first treatment attempt with an antidepressant medication. The NIMH-funded Treatment of Resistant Depression in Adolescents (TORDIA) study was designed to test second-step treatment strategies for these teens.

In TORDIA, 334 teens who did not get well after taking a type of antidepressant called a selective serotonin reuptake inhibitor (SSRI) before the trial were randomly assigned to one of four treatments for 12 weeks:

  • Switch to another SSRI
  • Switch to venlafaxine, a different type of antidepressant
  • Switch to another SSRI and add cognitive behavioral therapy (CBT), a type of psychotherapy
  • Switch to venlafaxine and add CBT

Results of the trial, which were reported in February 2008, showed that the teens who received medication plus CBT were more likely to get well than those who switched medications only. In this most recent data analysis, Joan Rosenbaum Asarnow, Ph.D., of the University of California Los Angeles, and colleagues aimed to identify how to better predict a teen's response to treatment, and any factors that might affect response.

Results of the Study

Many predictors were similar to those found in studies of first-step treatments, such as the NIMH-funded Treatment for Adolescents with Depression Study (TADS), underscoring the importance of early treatment before the depression becomes chronic. For instance, like in TADS, teens in the TORDIA study were less likely to respond to treatment if they had very severe depression or higher levels of suicidal thinking. In addition, teens prone to self-harming behavior and family conflict were less likely to respond to treatment.

In contrast to TADS, however, the TORDIA teens with coexisting disorders, such as an anxiety disorder, attention deficit hyperactivity disorder (ADHD), or others, did respond to TORDIA's combination therapy. The researchers theorize that in this SSRI-resistant group, adding a CBT framework may have helped the teens deal with difficulties associated with coexisting disorders. In addition, the type of CBT used in the trial included general strategies for coping with a wide range of disorders, such as ways of solving problems and improving social functioning. Because community settings often must treat patients with coexisting disorders, this finding supports the use of CBT with patients who have complex diagnoses, according to the researchers.

Combination treatment, however, was not as beneficial for teens with a history of abuse, and those reporting high levels of hopelessness. This suggests a need to strengthen treatment strategies for teens suffering from these problems, said the researchers.


Knowing predictors and moderators of treatment response may help identify the most appropriate treatment for each individual.

"Selecting the optimal treatment for teens with depression is particularly crucial for those who do not respond to an initial treatment, because when depression is unremitting, teens and their parents often give up, which makes them less likely to stick to treatment," concluded Dr. Asarnow. "With this new data, personalizing depression treatment based on a teen's individual circumstances becomes a real possibility."

What's Next

Future studies can help confirm these findings and therefore contribute to a more personalized approach to the treatment of depression in adolescence. In addition, the researchers conclude that findings from this study can inform efforts to build better treatment strategies.


Asarnow JR, Emslie G, Clarke G, Wagner KD, Spirito A, Vitiello B, Iyengar S, Shamseddeen W, Ritz L, Birmaher B, Ryan N, Kennard B, Mayes T, DeBar L, McCracken J, Strober M, Suddath R, Leonard H, Porta G, Keller M, Brent D. Treatment of SSRI-resistant depression in adolescents: predictors and moderators of treatment response . Journal of the American Academy of Child and Adolescent Psychiatry. Published online ahead of print February 4, 2009.