Treatment of SSRI-Resistant Depression In Adolescents (TORDIA) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Depression	Drug: Fluoxetine Drug: Venlafaxine Behavioral: Cognitive Behavioral Therapy (CBT) Drug: Citalopram	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Treatment of SSRI-Resistant Depression in Adolescents (TORDIA)

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants Depression

Drug Information available for: Fluoxetine Fluoxetine hydrochloride Citalopram hydrobromide Citalopram Venlafaxine Venlafaxine hydrochloride Escitalopram oxalate

U.S. FDA Resources

Further study details as provided by National Institute of Mental Health (NIMH):

Enrollment:	334
Study Start Date:	January 2001
Study Completion Date:	January 2007

Arms	Assigned Interventions
Experimental: 1 Participants whose depression does not respond to an initial SSRI will switch to an alternative SSRI.	Drug: Fluoxetine Standard anti-depressant treatment with the SSRI fluoxetine Other Name: Prozac Drug: Citalopram Standard anti-depressant treatment with the SSRI fluoxetine Other Name: Celexa
Experimental: 2 Participants whose depression does not respond to an initial SSRI will switch to a different non-SSRI antidepressant.	Drug: Venlafaxine Standard antidepressant treatment with the non-SSRI medication venlafaxine Other Name: Effexor XR
Experimental: 3 Participants whose depression does not respond to an initial SSRI will switch to an alternative SSRI and receive cognitive behavioral therapy (CBT).	Drug: Fluoxetine Standard anti-depressant treatment with the SSRI fluoxetine Other Name: Prozac Behavioral: Cognitive Behavioral Therapy (CBT) CBT addresses maladaptive beliefs in order to encourage behavioral change Drug: Citalopram Standard anti-depressant treatment with the SSRI fluoxetine Other Name: Celexa
Experimental: 4 Participants whose depression does not respond to an initial SSRI will switch to a different non-SSRI antidepressant and receive CBT.	Drug: Venlafaxine Standard antidepressant treatment with the non-SSRI medication venlafaxine Other Name: Effexor XR Behavioral: Cognitive Behavioral Therapy (CBT) CBT addresses maladaptive beliefs in order to encourage behavioral change

Detailed Description:

The TORDIA study aims to develop useful clinical guidelines for the care and management of adolescent depression. Adolescents ages 12 to 18, currently taking a prescribed selective serotonin reuptake inhibitor (SSRI) and still experiencing depression, participate in a 12-week randomized treatment study that includes one of four conditions: (1) switching to an alternative SSRI, (2) switching to a different non-SSRI antidepressant, (3) switching to an alternative SSRI and receiving cognitive behavioral therapy (CBT), or (4) switching to a different non-SSRI antidepressant and receiving CBT. This is a double-blind study, which means that neither the participant nor the clinical staff will know which of the three possible medications has been assigned. Participants who respond to the assigned treatment will receive 12 additional weeks of the same treatment. Those who do not appear to be getting better will be offered 12 weeks of an alternative, individualized treatment plan based on each participant's particular needs. All participants will receive follow-up psychiatric evaluations for 12 months after the 12-week continuation phase of the study, regardless of treatment adherence.

Eligibility

Ages Eligible for Study:	12 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00018902

Locations

United States, California
University of California at Los Angeles
Los Angeles, California, United States, 90095-6967
United States, Oregon
Kaiser Permanente Center for Health Research
Portland, Oregon, United States, 97227-1098
United States, Pennsylvania
Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Brown University
Providence, Rhode Island, United States, 02906
United States, Texas
University of Texas - Southwestern Medical Center
Dallas, Texas, United States, 75390-8589
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0188

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

David A. Brent, MD

Western Psychiatric Institute and Clinic (Data Coordinating Center)

More Information

Additional Information:

Click here for more information about this study: Treatment of Resistant Depression in Adolescents This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

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):901-13.

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.

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.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Epub 2012 Mar 3.

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. Epub 2012 Jan 30.

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. Epub 2012 Jan 17.

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. Epub 2012 Jan 17.

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. Epub 2011 Sep 9.

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. Epub 2011 Jun 11.

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. Epub 2011 Mar 9.

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.

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. Epub 2011 Jan 14.

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.

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. Epub 2010 May 17.

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. Epub 2009 Dec 15.

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.

Responsible Party:	David A. Brent, MD, Western Psychiatric Institute and Clinic (Data Coordinating Center)
ClinicalTrials.gov Identifier:	NCT00018902 History of Changes
Other Study ID Numbers:	U01 MH61835, TORDIA, DSIR B4-ARD, MH61835
Study First Received:	July 10, 2001
Last Updated:	December 23, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Mental Health (NIMH):

Depressive Disorder
Adolescents
Teenagers
Teens
Cognitive Behavior Therapy

Additional relevant MeSH terms:

Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Citalopram
Fluoxetine
Venlafaxine
Dexetimide
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antidepressive Agents, Second-Generation

Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on May 23, 2013