Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: The TORDIA randomized controlled trial

David Brent, Graham Emslie, Greg Clarke, Karen Dineen Wagner, Joan Rosenbaum Asarnow, Marty Keller, Benedetto Vitiello, Louise Ritz, Satish Iyengar, Kaleab Abebe, Boris Birmaher, Neal Ryan, Betsy Kennard, Carroll Hughes, Lynn DeBar, James McCracken, Michael Strober, Robert Suddath, Anthony Spirito, Henrietta LeonardNadine Melhem, Giovanna Porta, Matthew Onorato, Jamie Zelazny

Research output: Contribution to journalArticlepeer-review

419 Scopus citations


Context: Only about 60% of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor (SSRI). There are no data to guide clinicians on subsequent treatment strategy. Objective: To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI. Design, Setting, and Participants: Randomized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI, conducted at 6 US academic and community clinics from 2000-2006. Interventions: Twelve weeks of: (1) switch to a second, different SSRI (paroxetine, citalopram, or fluoxetine, 20-40 mg); (2) switch to a different SSRI plus cognitive behavioral therapy; (3) switch to venlafaxine (150-225 mg); or (4) switch to venlafaxine plus cognitive behavioral therapy. Main Outcome Measures: Clinical Global Impressions- Improvement score of 2 or less (much or very much improved) and a decrease of at least 50% in the Children's Depression Rating Scale-Revised (CDRS-R); and change in CDRS-R over time. Results: Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate (54.8%; 95% confidence interval [CI], 47%-62%) than a medication switch alone (40.5%; 95% CI, 33%-48%; P = .009), but there was no difference in response rate between venlafaxine and a second SSRI (48.2%; 95% CI, 41%-56% vs 47.0%; 95% CI, 40%-55%; P = .83). There were no differential treatment effects on change in the CDRS-R, self-rated depressive symptoms, suicidal ideation, or on the rate of harm-related or any other adverse events. There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment. Conclusions: For adolescents with depression not responding to an adequate initial treatment with an SSRI, the combination of cognitive behavioral therapy and a switch to another antidepressant resulted in a higher rate of clinical response than did a medication switch alone. However, a switch to another SSRI was just as efficacious as a switch to venlafaxine and resulted in fewer adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT00018902.

Original languageEnglish (US)
Pages (from-to)901-913
Number of pages13
JournalJAMA - Journal of the American Medical Association
Issue number8
StatePublished - Feb 27 2008

ASJC Scopus subject areas

  • General Medicine


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