Substance Use and the Treatment of Resistant Depression in Adolescents

Benjamin I. Goldstein, Wael Shamseddeen, Anthony Spirito, Graham Emslie, Greg Clarke, Karen Dineen Wagner, Joan Rosenbaum Asarnow, Benedetto Vitiello, Neal Ryan, Boris Birmaher, Taryn Mayes, Matthew Onorato, Jamie Zelazny, David A. Brent

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Objective: Despite the known association between substance use disorders and major depressive disorder (MDD) among adolescents, little is known regarding substance use among adolescents with MDD. Method: Youths with MDD who had not improved after an adequate selective serotonin reuptake inhibitor trial (N = 334) were enrolled in the Treatment of SSRI-Resistant Depression in Adolescents trial. Analyses examined substance use (via the Drug Use Severity Index) and changes therein in relation to treatment and depressive symptoms. Adolescents meeting substance use disorder criteria via the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version at baseline were excluded. Results: Substance use was common: 28.1% reported repeated experimentation at baseline. Substance-related impairment was associated with baseline depression severity, older age, physical/sexual abuse, family conflict, hopelessness, and comorbid oppositional defiant disorder/conduct disorder. There was significant improvement in substance-related impairment among adolescents who responded to MDD treatment. Baseline suicidal ideation was higher among the subjects who progressed to high substance-related impairment (≥75th percentile) versus those whose substance-related impairment remained low (<75th percentile), and parental depressive symptoms predicted persistence of high substance-related impairment during the study. The MDD response was best among the adolescents with low 12 week substance-related impairment scores regardless of whether they had high or low baseline substance-related impairment. There were no significant differential effects of specific treatments, pharmacological or cognitive-behavioral therapy, on substance use. Conclusions: Substance use is common among adolescents with treatment-resistant MDD. The subjects who had persistently low substance-related impairment or who demonstrated reduced substance-related impairment had better MDD treatment response, although the direction of this association is uncertain.

Original languageEnglish (US)
Pages (from-to)1182-1192
Number of pages11
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number12
StatePublished - Dec 2009


  • depression
  • substance use
  • treatment

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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