A 5-year, 6-site study, consisting of 6 interlocking R01 applications is proposed to study the treatment of SSRI-resistant depression in 400 adolescents. Subjects will be those with DSM-IV MDD, currently in treatment, and still depressed despite at least 6 weeks of treatment, at least 2 weeks of which are at a higher dosage (40mg) of either paroxetine or fluoxetine and the remainder at an adequate dosage (20 mg). We focus on these two SSRIs because they are most commonly used drugs in this class, and the only two for which efficacy has been demonstrated for the treatment of adolescent depression. After an initial assessment, the adolescents will be observed at the higher dosage of SSRI for an additional 2 weeks and then be reassessed. Those who show no significant response over that time (decrease in CDRS-R equal to or <20%) will be tapered from their current regimen and entered into the protocol. These 400 subjects will be assigned to one of four conditions to be delivered over 12 weeks. The rate of clinically acceptable response to treatment (defined as a CGI-I equal to or <2 and equal to or >50% decrease in the CDRS-R) will be compared across the 4 cells in a 2x2 factorial design: (l) switch within SSRI class (those On paroxetine switch to fluoxetine; those on fluoxetine switch to paroxetine); (2) switch to a different class of agent (venlafaxine); (3) switch within SSRI class plus receive cognitive behavior therapy (CBT), and; (4) switch to a different class of agent (venlafaxine) plus CBT. Subjects who show a clinically acceptable response will receive l2 additional weeks of continuation treatment with the same intervention as in the acute phase. Non- responders will be offered 12 weeks of open treatment. All subjects will be followed up for l2 months after the continuation phase, regardless of treatment compliance. We hypothesize that there will be a medication effect (venlafaxine superior to SSRI switch), a CBT effect (CBT + medication superior to medication alone), and that CBT + venlafaxine superior to the other 3 cells. In addition, we hypothesize that the rate of relapse and recurrence will be lower in the CBT treated cells. The six sites participating and the number of subjects to be enrolled are: Brown (n=40), the site of this application, Dallas (n=80), Galveston (n=80), Oregon (n=80), UCLA (n=40), and Pittsburgh (n=80), with the latter being the coordinating site for the overall study.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01MH062014-01
Application #
6190403
Study Section
Special Emphasis Panel (ZMH1-CRB-J (03))
Program Officer
Vitiello, Benedetto
Project Start
2000-09-22
Project End
2005-08-31
Budget Start
2000-09-22
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$235,641
Indirect Cost
Name
Brown University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Hilton, Robert C; Rengasamy, Manivel; Mansoor, Brandon et al. (2013) 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 52:482-92
Mansoor, Brandon; Rengasamy, Manivel; Hilton, Robert et al. (2013) The bidirectional relationship between body mass index and treatment outcome in adolescents with treatment-resistant depression. J Child Adolesc Psychopharmacol 23:458-67
Rengasamy, Manivel; Mansoor, Brandon M; Hilton, Robert et al. (2013) The bi-directional relationship between parent-child conflict and treatment outcome in treatment-resistant adolescent depression. J Am Acad Child Adolesc Psychiatry 52:370-7
Wagner, Karen Dineen; Asarnow, Joan Rosenbaum; Vitiello, Benedetto et al. (2012) Out of the black box: treatment of resistant depression in adolescents and the antidepressant controversy. J Child Adolesc Psychopharmacol 22:5-10
McMakin, Dana L; Olino, Thomas M; Porta, Giovanna et al. (2012) Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression. J Am Acad Child Adolesc Psychiatry 51:404-11
Maalouf, Fadi T; Porta, Giovanna; Vitiello, Benedetto et al. (2012) Do sub-syndromal manic symptoms influence outcome in treatment resistant depression in adolescents? A latent class analysis from the TORDIA study. J Affect Disord 138:86-95
Shamseddeen, Wael; Clarke, Gregory; Keller, Martin B et al. (2012) Adjunctive sleep medications and depression outcome in the treatment of serotonin-selective reuptake inhibitor resistant depression in adolescents study. J Child Adolesc Psychopharmacol 22:29-36
Lynch, Frances L; Dickerson, John F; Clarke, Greg et al. (2011) 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 68:253-62
Sakolsky, Dara J; Perel, James M; Emslie, Graham J et al. (2011) Antidepressant exposure as a predictor of clinical outcomes in the Treatment of Resistant Depression in Adolescents (TORDIA) study. J Clin Psychopharmacol 31:92-7
Shamseddeen, Wael; Clarke, Gregory; Wagner, Karen Dineen et al. (2011) Treatment-resistant depressed youth show a higher response rate if treatment ends during summer school break. J Am Acad Child Adolesc Psychiatry 50:1140-8

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