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The TORDIA Randomized Controlled Trial

David Brent, MD; Graham Emslie, MD; Greg Clarke, PhD; Karen Dineen Wagner, MD, PhD; Joan Rosenbaum Asarnow, PhD; Marty Keller, MD; Benedetto Vitiello, MD; Louise Ritz, MBA; Satish Iyengar, PhD; Kaleab Abebe, MA; Boris Birmaher, MD; Neal Ryan, MD; Betsy Kennard, PsyD; Carroll Hughes, PhD; Lynn DeBar, PhD; James McCracken, MD; Michael Strober, PhD; Robert Suddath, MD; Anthony Spirito, PhD; Henrietta Leonard, MD; Nadine Melhem, PhD; Giovanna Porta, MS; Matthew Onorato, LCSW; Jamie Zelazny, MPH, RN

JAMA. 2008;299(8):901-913.

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

Author Affiliations: University of Pittsburgh, Pittsburgh, Pennsylvania (Drs Brent, Iyengar, Birmaher, Ryan, and Melhem, Messrs Abebe and Onorato, and Mss Porta and Zelazny); University of Texas Southwestern Medical Center at Dallas (Drs Emslie, Kennard, and Hughes); Kaiser Permanente Center for Health Research, Portland, Oregon (Drs Clarke and DeBar); The University of Texas Medical Branch, Galveston (Dr Wagner); University of California, Los Angeles (Drs Rosenbaum Asarnow, McCracken, Strober, and Suddath); Brown University, Providence, Rhode Island (Drs Keller, Spirito, and Leonard); and National Institute of Mental Health, Bethesda, Maryland (Dr Vitiello and Ms Ritz); Mr Onorato is now with Nationwide Children’s Hospital, Columbus, Ohio.
Deceased.

RELATED LETTERS

SSRI Tapering and Suicidal Ideation in the TORDIA Study for Treatment of Depressed Adolescents
Ion Anghelescu and Francesca Regen
JAMA. 2008;299(23):2745-2746.
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SSRI Tapering and Suicidal Ideation in the TORDIA Study for Treatment of Depressed Adolescents—Reply
David Brent and Karen Dineen Wagner
JAMA. 2008;299(23):2746.
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