Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: Predictors and moderators of treatment response

Joan Rosenbaum Asaknow, Graham Emslie, Greg Clarke, Karen Dineen Wagner, Anthony Spirito, Benedetto Vitiello, Satish Iyengar, Wael Shamseddeen, Louise Ritz, Boris Birmaher, Neal Ryan, Betsy Kennard, Taryn Mayes, Lynn DeBar, James McCracken, Michael Strober, Robert Suddath, Henrietta Leonard, Giovanna Porta, Martin KellerDavid Brent

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


Objective: To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we conducted a randomized controlled trial evaluating alternative treatment strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with medication change was associated with higher rates of positive response to short-term (12-week) treatment than medication alone. This study examines predictors and moderators of treatment response, with the goal of informing efforts to match youths to optimal treatment strategies. Method: Youths who had not improved during an adequate SSRI trial (N= 334) were randomized to an alternative SSRI, an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses examined predictors and moderators of treatment response. Results: Less severe depression, less family conflict, and absence of nonsuicidal self-injurious behavior predicted better treatment response status. Significant moderators of response to CBT + medication (combined) treatment were number of comorbid disorders and abuse history; hopelessness was marginally significant. The CBT/combined treatment superiority over medication alone was more evident among youths who had more cornorbid disorders (particularly attention-deficit/hyperactivity disorder and anxiety disorders), no abuse history, and lower hopelessness. Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer prestudy pharmacotherapy. Conclusions: Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders. Given the additional costs of adding CBT to medication, consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment.

Original languageEnglish (US)
Pages (from-to)330-339
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number3
StatePublished - Mar 2009


  • Adolescents
  • Cognitive-behavioral therapy
  • Depression
  • Treatment-resistant

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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