Treatment of SSRI-Resistant Depression In Adolescents (TORDIA)

NCT00018902 | Completed Phase 2 DMC

• 4 other identifiers: U01MH061835TORDIADSIR B4-ARDMH61835
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of the study is to determine how best to treat adolescents with depression that is "resistant" to the first SSRI antidepressant they have tried. Participants receive one of three other antidepressant medications, either alone or in combination with cognitive behavioral therapy.

Conditions

Depression

Keywords

Depressive Disorder; Adolescents; Teenagers; Teens; Cognitive Behavior Therapy

Study Arms (4)

1

EXPERIMENTAL

Participants whose depression does not respond to an initial SSRI will switch to an alternative SSRI.

Drug: Fluoxetine; Drug: Citalopram

2

EXPERIMENTAL

Participants whose depression does not respond to an initial SSRI will switch to a different non-SSRI antidepressant.

Drug: Venlafaxine

3

EXPERIMENTAL

Participants whose depression does not respond to an initial SSRI will switch to an alternative SSRI and receive cognitive behavioral therapy (CBT).

Drug: Fluoxetine; Behavioral: Cognitive Behavioral Therapy (CBT); Drug: Citalopram

4

EXPERIMENTAL

Participants whose depression does not respond to an initial SSRI will switch to a different non-SSRI antidepressant and receive CBT.

Drug: Venlafaxine; Behavioral: Cognitive Behavioral Therapy (CBT)

Interventions

Fluoxetine DRUG

Standard anti-depressant treatment with the SSRI fluoxetine

Also known as: Prozac

1; 3

Venlafaxine DRUG

Standard antidepressant treatment with the non-SSRI medication venlafaxine

Also known as: Effexor XR

2; 4

Cognitive Behavioral Therapy (CBT) BEHAVIORAL

CBT addresses maladaptive beliefs in order to encourage behavioral change

3; 4

Citalopram DRUG

Standard anti-depressant treatment with the SSRI fluoxetine

Also known as: Celexa

1; 3

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

* between the ages of 12 and 18 years 11 months * currently in treatment for depression * taking Prozac,Zoloft, Luvox, Lexapro, Celexa or Paxil (Oregon and Rhode Island sites only) * still feeling depressed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (6)

University of California at Los Angeles

Los Angeles, California, 90095-6967, United States

Location

Kaiser Permanente Center for Health Research

Portland, Oregon, 97227-1098, United States

Location

Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Brown University

Providence, Rhode Island, 02906, United States

Location

University of Texas - Southwestern Medical Center

Dallas, Texas, 75390-8589, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0188, United States

Location

Related Publications (26)

• Brent DA, Holder D, Kolko D, Birmaher B, Baugher M, Roth C, Iyengar S, Johnson BA. A clinical psychotherapy trial for adolescent depression comparing cognitive, family, and supportive therapy. Arch Gen Psychiatry. 1997 Sep;54(9):877-85. doi: 10.1001/archpsyc.1997.01830210125017.

  PMID: 9294380 BACKGROUND

• Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, Rintelmann J. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry. 1997 Nov;54(11):1031-7. doi: 10.1001/archpsyc.1997.01830230069010.

  PMID: 9366660 BACKGROUND

• Keller MB, Ryan ND, Birmaher B, Klein RG, Strober M, Wagner KD, Weller EB: Paroxetine and imipramine in the treatment of adolescent depression. New Research Program Abstracts. Annual Meeting of the American Psychiatric Association [123], 1998.

  BACKGROUND

• Wagner KD, Asarnow JR, Vitiello B, Clarke G, Keller M, Emslie GJ, Ryan N, Porta G, Iyengar S, Ritz L, Zelanzny J, Onorato M, Brent D. Out of the black box: treatment of resistant depression in adolescents and the antidepressant controversy. J Child Adolesc Psychopharmacol. 2012 Feb;22(1):5-10. doi: 10.1089/cap.2011.0045. Epub 2012 Jan 17.

  PMID: 22251022 BACKGROUND

• Brent D, Emslie G, Clarke G, Wagner KD, Asarnow JR, Keller M, Vitiello B, Ritz L, Iyengar S, Abebe K, Birmaher B, Ryan N, Kennard B, Hughes C, DeBar L, McCracken J, Strober M, Suddath R, Spirito A, Leonard H, Melhem N, Porta G, Onorato M, Zelazny J. Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial. JAMA. 2008 Feb 27;299(8):901-913. doi: 10.1001/jama.299.8.901.

  PMID: 18314433 RESULT

• Brent DA, Emslie GJ, Clarke GN, Asarnow J, Spirito A, Ritz L, Vitiello B, Iyengar S, Birmaher B, Ryan ND, Zelazny J, Onorato M, Kennard B, Mayes TL, Debar LL, McCracken JT, Strober M, Suddath R, Leonard H, Porta G, Keller MB. Predictors of spontaneous and systematically assessed suicidal adverse events in the treatment of SSRI-resistant depression in adolescents (TORDIA) study. Am J Psychiatry. 2009 Apr;166(4):418-26. doi: 10.1176/appi.ajp.2008.08070976. Epub 2009 Feb 17.

  PMID: 19223438 RESULT

• Asarnow JR, Emslie G, Clarke G, Wagner KD, Spirito A, Vitiello B, Iyengar S, Shamseddeen W, Ritz L, Birmaher B, Ryan N, Kennard B, Mayes T, DeBar L, McCracken J, Strober M, Suddath R, Leonard H, Porta G, Keller M, Brent D. Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: predictors and moderators of treatment response. J Am Acad Child Adolesc Psychiatry. 2009 Mar;48(3):330-339. doi: 10.1097/chi.0b013e3181977476.

  PMID: 19182688 RESULT

• Goldstein BI, Shamseddeen W, Spirito A, Emslie G, Clarke G, Wagner KD, Asarnow JR, Vitiello B, Ryan N, Birmaher B, Mayes T, Onorato M, Zelazny J, Brent DA. Substance use and the treatment of resistant depression in adolescents. J Am Acad Child Adolesc Psychiatry. 2009 Dec;48(12):1182-92. doi: 10.1097/CHI.0b013e3181bef6e8.

  PMID: 19858762 RESULT

• Spirito A, Abebe KZ, Iyengar S, Brent D, Vitiello B, Clarke G, Wagner KD, Asarnow J, Emslie G, Keller M. Sources of site differences in the efficacy of a multisite clinical trial: the Treatment of SSRI-Resistant Depression in Adolescents. J Consult Clin Psychol. 2009 Jun;77(3):439-50. doi: 10.1037/a0014834.

  PMID: 19485586 RESULT

• Kennard BD, Clarke GN, Weersing VR, Asarnow JR, Shamseddeen W, Porta G, Berk M, Hughes JL, Spirito A, Emslie GJ, Keller MB, Wagner KD, Brent DA. Effective components of TORDIA cognitive-behavioral therapy for adolescent depression: preliminary findings. J Consult Clin Psychol. 2009 Dec;77(6):1033-41. doi: 10.1037/a0017411.

  PMID: 19968380 RESULT

• Brent D, Melhem N, Ferrell R, Emslie G, Wagner KD, Ryan N, Vitiello B, Birmaher B, Mayes T, Zelazny J, Onorato M, Devlin B, Clarke G, DeBar L, Keller M. Association of FKBP5 polymorphisms with suicidal events in the Treatment of Resistant Depression in Adolescents (TORDIA) study. Am J Psychiatry. 2010 Feb;167(2):190-7. doi: 10.1176/appi.ajp.2009.09040576. Epub 2009 Dec 15.

  PMID: 20008943 RESULT

• Emslie GJ, Mayes T, Porta G, Vitiello B, Clarke G, Wagner KD, Asarnow JR, Spirito A, Birmaher B, Ryan N, Kennard B, DeBar L, McCracken J, Strober M, Onorato M, Zelazny J, Keller M, Iyengar S, Brent D. Treatment of Resistant Depression in Adolescents (TORDIA): week 24 outcomes. Am J Psychiatry. 2010 Jul;167(7):782-91. doi: 10.1176/appi.ajp.2010.09040552. Epub 2010 May 17.

  PMID: 20478877 RESULT

• Asarnow JR, Porta G, Spirito A, Emslie G, Clarke G, Wagner KD, Vitiello B, Keller M, Birmaher B, McCracken J, Mayes T, Berk M, Brent DA. Suicide attempts and nonsuicidal self-injury in the treatment of resistant depression in adolescents: findings from the TORDIA study. J Am Acad Child Adolesc Psychiatry. 2011 Aug;50(8):772-81. doi: 10.1016/j.jaac.2011.04.003. Epub 2011 Jun 11.

  PMID: 21784297 RESULT

• Sakolsky DJ, Perel JM, Emslie GJ, Clarke GN, Wagner KD, Vitiello B, Keller MB, Birmaher B, Asarnow JR, Ryan ND, McCracken JT, Strober MJ, Iyengar S, Porta G, Brent DA. Antidepressant exposure as a predictor of clinical outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) study. J Clin Psychopharmacol. 2011 Feb;31(1):92-7. doi: 10.1097/JCP.0b013e318204b117.

  PMID: 21192150 RESULT

• Shamseddeen W, Asarnow JR, Clarke G, Vitiello B, Wagner KD, Birmaher B, Keller MB, Emslie G, Iyengar S, Ryan ND, McCracken JT, Porta G, Mayes T, Brent DA. Impact of physical and sexual abuse on treatment response in the Treatment of Resistant Depression in Adolescent Study (TORDIA). J Am Acad Child Adolesc Psychiatry. 2011 Mar;50(3):293-301. doi: 10.1016/j.jaac.2010.11.019. Epub 2011 Jan 14.

  PMID: 21334569 RESULT

• Vitiello B, Emslie G, Clarke G, Wagner KD, Asarnow JR, Keller MB, Birmaher B, Ryan ND, Kennard B, Mayes TL, DeBar L, Lynch F, Dickerson J, Strober M, Suddath R, McCracken JT, Spirito A, Onorato M, Zelazny J, Porta G, Iyengar S, Brent DA. Long-term outcome of adolescent depression initially resistant to selective serotonin reuptake inhibitor treatment: a follow-up study of the TORDIA sample. J Clin Psychiatry. 2011 Mar;72(3):388-96. doi: 10.4088/JCP.09m05885blu.

  PMID: 21208583 RESULT

• Woldu H, Porta G, Goldstein T, Sakolsky D, Perel J, Emslie G, Mayes T, Clarke G, Ryan ND, Birmaher B, Wagner KD, Asarnow JR, Keller MB, Brent D. Pharmacokinetically and clinician-determined adherence to an antidepressant regimen and clinical outcome in the TORDIA trial. J Am Acad Child Adolesc Psychiatry. 2011 May;50(5):490-8. doi: 10.1016/j.jaac.2011.01.018. Epub 2011 Mar 9.

  PMID: 21515198 RESULT

• Maalouf FT, Porta G, Vitiello B, Emslie G, Mayes T, Clarke G, Wagner KD, Asarnow JR, Spirito A, Keller M, Birmaher B, Ryan N, Shamseddeen W, Iyengar S, Brent D. Do sub-syndromal manic symptoms influence outcome in treatment resistant depression in adolescents? A latent class analysis from the TORDIA study. J Affect Disord. 2012 Apr;138(1-2):86-95. doi: 10.1016/j.jad.2011.12.021. Epub 2012 Jan 30.

  PMID: 22284022 RESULT

• Lynch FL, Dickerson JF, Clarke G, Vitiello B, Porta G, Wagner KD, Emslie G, Asarnow JR Jr, Keller MB, Birmaher B, Ryan ND, Kennard B, Mayes T, DeBar L, McCracken JT, Strober M, Suddath RL, Spirito A, Onorato M, Zelazny J, Iyengar S, Brent D. Incremental cost-effectiveness of combined therapy vs medication only for youth with selective serotonin reuptake inhibitor-resistant depression: treatment of SSRI-resistant depression in adolescents trial findings. Arch Gen Psychiatry. 2011 Mar;68(3):253-62. doi: 10.1001/archgenpsychiatry.2011.9.

  PMID: 21383263 RESULT

• Shamseddeen W, Clarke G, Wagner KD, Ryan ND, Birmaher B, Emslie G, Asarnow JR, Porta G, Mayes T, Keller MB, Brent DA. Treatment-resistant depressed youth show a higher response rate if treatment ends during summer school break. J Am Acad Child Adolesc Psychiatry. 2011 Nov;50(11):1140-8. doi: 10.1016/j.jaac.2011.07.022. Epub 2011 Sep 9.

  PMID: 22024002 RESULT

• Shamseddeen W, Clarke G, Keller MB, Wagner KD, Birmaher B, Emslie GJ, Ryan N, Asarnow JR, Porta G, Brent DA. Adjunctive sleep medications and depression outcome in the treatment of serotonin-selective reuptake inhibitor resistant depression in adolescents study. J Child Adolesc Psychopharmacol. 2012 Feb;22(1):29-36. doi: 10.1089/cap.2011.0027. Epub 2012 Jan 17.

  PMID: 22251024 RESULT

• McMakin DL, Olino TM, Porta G, Dietz LJ, Emslie G, Clarke G, Wagner KD, Asarnow JR, Ryan ND, Birmaher B, Shamseddeen W, Mayes T, Kennard B, Spirito A, Keller M, Lynch FL, Dickerson JF, Brent DA. Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression. J Am Acad Child Adolesc Psychiatry. 2012 Apr;51(4):404-11. doi: 10.1016/j.jaac.2012.01.011. Epub 2012 Mar 3.

  PMID: 22449646 RESULT

• Rengasamy M, Mansoor BM, Hilton R, Porta G, He J, Emslie GJ, Mayes T, Clarke GN, Wagner KD, Keller MB, Ryan ND, Birmaher B, Shamseddeen W, Asarnow JR, Brent DA. The bi-directional relationship between parent-child conflict and treatment outcome in treatment-resistant adolescent depression. J Am Acad Child Adolesc Psychiatry. 2013 Apr;52(4):370-7. doi: 10.1016/j.jaac.2013.01.012.

  PMID: 23582868 RESULT

• Hilton RC, Rengasamy M, Mansoor B, He J, Mayes T, Emslie GJ, Porta G, Clarke GN, Wagner KD, Birmaher B, Keller MB, Ryan N, Shamseddeen W, Asarnow JR, Brent DA. Impact of treatments for depression on comorbid anxiety, attentional, and behavioral symptoms in adolescents with selective serotonin reuptake inhibitor-resistant depression. J Am Acad Child Adolesc Psychiatry. 2013 May;52(5):482-92. doi: 10.1016/j.jaac.2013.02.013. Epub 2013 Apr 4.

  PMID: 23622849 RESULT

• Mansoor B, Rengasamy M, Hilton R, Porta G, He J, Spirito A, Emslie GJ, Mayes TL, Clarke G, Wagner KD, Shamseddeen W, Birmaher B, Ryan N, Brent D. The bidirectional relationship between body mass index and treatment outcome in adolescents with treatment-resistant depression. J Child Adolesc Psychopharmacol. 2013 Sep;23(7):458-67. doi: 10.1089/cap.2012.0095. Epub 2013 Sep 11.

  PMID: 24024532 RESULT

• Perloe A, Esposito-Smythers C, Curby TW, Renshaw KD. Concurrent trajectories of change in adolescent and maternal depressive symptoms in the TORDIA study. J Youth Adolesc. 2014 Apr;43(4):612-28. doi: 10.1007/s10964-013-9999-0. Epub 2013 Aug 22.

  PMID: 23975354 DERIVED

Related Links

• Click here for more information about this study: Treatment of Resistant Depression in Adolescents

MeSH Terms

Conditions

Depression; Depressive Disorder

Interventions

Fluoxetine; Venlafaxine Hydrochloride; Cognitive Behavioral Therapy; Citalopram

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Phenethylamines; Ethylamines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• David A. Brent, MD

  Western Psychiatric Institute and Clinic (Data Coordinating Center)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 10, 2001
• First Posted: July 12, 2001
• Study Start: January 1, 2001
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2007
• Last Updated: March 12, 2014

Record last verified: 2014-03

Locations

US (6)