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Long-Term Outcome of Adolescent Depression Initially Resistant to Selective Serotonin Reuptake Inhibitor Treatment: A Follow-Up Study of the TORDIA Sample

Benedetto Vitiello, MD; Graham Emslie, MD; Gregory Clarke, PhD; Karen Dineen Wagner, MD, PhD; Joan R. Asarnow, PhD; Martin B. Keller, MD; Boris Birmaher, MD; Neal D. Ryan, MD; Betsy Kennard, PsyD; Taryn L. Mayes, MS; Lynn DeBar, PhD; Frances Lynch, PhD; John Dickerson, PhD; Michael Strober, PhD; Robert Suddath, MD; James T. McCracken, MD; Anthony Spirito, PhD; Matthew Onorato, LCSW; Jamie Zelazny, MPH, RN; Giovanna Porta, MS; Satish Iyengar, PhD; and David A. Brent, MD

Published: November 16, 2010

Article Abstract

Background: We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive-behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while nonresponders were given open treatment.

Method: For the current study, patients were reassessed 48 (n = 116) and 72 (n = 130) weeks from intake. Data were gathered from February 2001 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology, and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE]), and relapse, as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed-effects regression models were applied to estimate remission, relapse, and functional recovery.

Results: By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRIs had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (P < .03). Participants with more severe depression, greater dysfunction, and alcohol or drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of nonremitters by the first 6 weeks of treatment (P < .001). Of the 130 participants in remission at week 24, 25.4% relapsed in the subsequent year.

Conclusions: While most adolescents achieved remission, more than one-third did not, and one-fourth of remitted patients experienced a relapse. More effective interventions are needed for patients who do not show robust improvement early in treatment.

Trial Registration: Identifier: NCT00018902

J Clin Psychiatry

Submitted: December 7, 2009; accepted March 25, 2010.

Online ahead of print: November 16, 2010 (doi:10.4088/JCP.09m05885blu).

Corresponding author: Benedetto Vitiello, MD, National Institute of Mental Health, Room 7147, 6001 Executive Blvd, Bethesda, MD 20892-9633 (

Volume: 71

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