This two-year, six-site, competitive renewal compares four strategies for the treatment of SSRI-resistant adolescent depression. We propose to complete our recruitment of 400 adolescents, aged 12-18, who continue to be depressed despite an adequate trial of one of the SSRI antidepressants currently used in community practice (i.e., fluoxetine, citalopram, escitalopram, sertraline). During this project period, we will empanel 100 adolescents with SSRI-resistant depression to complete our target recruitment. The rates of clinically acceptable response (defined as a CGI-I < 2, CGIS < 3, and > 50% decrease in the CDRS-R), slope of decrease of depressive symptoms on the CDRS-R, and direct cost of treatment per unit of improvement will be compared across the 4 cells in a 2x2 factorial design: (1) switch within SSRI class (those on citalopram switch to fluoxetine; those on fluoxetine switch to citalopram; those on sertraline switch randomly to either fluoxetine or citalopram); (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. """"""""Adequate treatment"""""""" with an SSRI is defined as > 8 weeks of total treatment, at least 4 weeks of which were at the equivalent of 20 mg of fluoxetine, and at least 4 weeks of which were at the equivalent > 40 mg of fluoxetine. In order to enter the study, subjects are assessed at two points in time 2 weeks apart, and must demonstrate sufficient severity (CDRS-R > 40, CGI-S > 4) and stability (decline in CDRS over two weeks < 30%). Subjects meeting these criteria will be cross-tapered gradually from their current regimen. The acute phase of treatment is 12 weeks, during which subjects can receive up to 40 mg of fluoxetine or citalopram, or 225 mg of venlafaxine. Subjects who show a clinically acceptable response will receive continuation treatment for an additional 12 weeks. All subjects, regardless of treatment compliance, will be assessed at intake, midpoint, and the end of acute treatment, and every 6 months thereafter for 1 year after the end of continuation treatment. We hypothesize that, with regard to adequate clinical response and rate of decline of depressive symptoms, venlafaxine will be superior to SSRI switch, CBT + medication will be superior to medication alone, and that CBT + venlafaxine will be superior to the other three cells. Significance. Because 40% of depressed adolescents do not respond to initial treatment with an SSRI, this is a common and serious public health problem. Subjects empaneled thus far are a high-risk group, with prevalent chronic depression and suicidality at intake. This is the only extant study to address the treatment of SSRI-resistant adolescent depression, and will be uniquely informative about treatment guidelines, the relative safety and efficacy of different antidepressants, and the value of adding CBT to medication treatment for this condition. This site is based in Pittsburgh, which also serves as the Data Coordinating Center for the study ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project--Cooperative Agreements (U01)
Project #
2U01MH061869-06
Application #
6926455
Study Section
Special Emphasis Panel (ZMH1-ERB-P (02))
Program Officer
Nottelmann, Editha
Project Start
2000-09-25
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
6
Fiscal Year
2005
Total Cost
$446,171
Indirect Cost
Name
Kaiser Foundation Research Institute
Department
Type
DUNS #
150829349
City
Oakland
State
CA
Country
United States
Zip Code
94612
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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