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Substance Use Associated with Low Response to Depression Treatment Among Teens

Science Update

teen boy asleep with book

Depressed teens who report low levels of impairment related to drug or alcohol use tended to respond better to depression treatment than depressed teens with higher levels substance-related impairment, according to an analysis of data from the NIMH-funded Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. However, it is unclear whether less substance-related impairment allowed for better response to depression treatment, or if better treatment response led to less substance-related impairment. The study was published in the December 2009 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.


Substance use is more common among teens with depression than among those without depression. Researchers have also found that depression can inhibit teens' response to treatment of substance abuse, and substance abuse is associated with a poorer response to treatment of depression. Still, few trials have examined how coexisting depression and substance use among teens may affect treatment outcomes for both.

In the TORDIA study, 334 teens who did not respond to 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 (Effexor), 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 were previously reported in February 2008. They showed that teens who received combination therapy, with either type of antidepressant, were more likely to improve than those on medication alone.

In this new analysis, Benjamin Goldstein, M.D., of the University of Toronto, and colleagues examined TORDIA data to determine the relationship, if any, between substance use, major depression and response to depression treatment. Substance use was defined as using alcohol or drugs without meeting criteria for having a full-blown substance abuse disorder. Teens who were diagnosed with a substance abuse disorder were excluded from the TORDIA study.

Results of the Study

Substance use was fairly common among TORDIA participants. At baseline, about 28 percent reported experimenting with drugs or alcohol. Those who showed more substance -related impairment were older, felt more hopeless, had greater family conflict, developed depression at an earlier age, were more likely to have a history of physical or sexual abuse, and were more likely to have coexisting oppositional defiant disorder (ODD) or conduct disorder (CD). Substance-related impairment included certain attitudes and behaviors such as craving the substance, feeling hooked on it, accidentally hurting oneself or others while using it, and other similar effects.

Participants with low levels of substance use and substance-related impairment throughout the study tended to respond better to depression treatment than those who showed persistently high or increasing levels of substance-related impairment. There were no significant differences in rates of substance use and impairment among the treatment groups.


This study is one of the first to examine the association between substance use and depression treatment among depressed teens. The findings are consistent with other studies that found depression severity to be associated with a history of physical or sexual abuse, coexisting ODD or CD, and substance-related impairment. However, the direction of the association is uncertain. The data could not determine whether low substance-related impairment facilitates improvement in depression symptoms, or whether improvement in depressed mood leads to a decrease in substance-related impairment.

What's Next

The authors caution that the study does not provide definitive conclusions about depression treatment and substance use. However, they do suggest that clinicians treating teens for depression screen for signs of substance use and address those issues as well, even if the teen does not meet criteria for a full-blown substance abuse disorder.


Goldstein BI, Shamseddeen W, Spirito A, Emslie G, Clarke G, Wagner KD, Asarnow JR, Vitiello B, Ryan N, Birmaher B, Mayes T, Onorato M, Zelazny J, Brent D. Substance use and the treatment of resistant depression in adolescents . Journal of the American Academy of Child and Adolescent Psychiatry. 2009 Dec. 48(12):1182-1192.