TADS is designed to compare the effectiveness of established treatments for teenagers suffering from major depressive disorder (MDD). The treatments are: psychotherapy ("talking therapy"); medication; and the combination of psychotherapy and medication. Altogether, 432 teenagers (both males and females) ages 12 to 17, will take part in this study at 12 sites in the United States.

The TADS design will provide answers to the following questions: What is the long-term effectiveness of medication treatment of teenagers who have major depression? What is the long-term effectiveness of a specific psychotherapy ("talking therapy) in the treatment of teenagers who have major depression? How does medication treatment compare with psychotherapy in terms of effectiveness, tolerability and teenager and family acceptance? And, What is the cost-effectiveness of medication, psychotherapy and combined treatments?

The medication being used in this study is called fluoxetine. Fluoxetine is also known as Prozac. Research has shown that medications like Prozac help depression in young persons. Fluoxetine has been approved by the FDA for use in the treatment of child and adolescent (ages 7 to 17 years) depression.

The psychotherapy or "talking therapy" being used in this study is called Cognitive Behavioral Therapy (CBT). CBT is a talking therapy that will teach both the teenager and his or her family member (e.g., parent) new skills to cope better with depression. Specific topics include education about depression and the causes of depression, setting goals, monitoring mood, increasing pleasant activities, social problem-solving, correcting negative thinking, negotiation, compromise and assertiveness. CBT sessions may also help with resolving disagreements as they affect families.

Condition	Treatment or Intervention	Phase
Major Depressive Disorder Depression	Drug: Fluoxetine  Behavior: Psychotherapy	Phase III

Further Study Details: 

Expected Total Enrollment:  432

TADS is a randomized controlled clinical trial that will compare the effectiveness of established treatments---cognitive-behavioral psychotherapy, medication management, and their combination---for adolescents suffering from major depressive disorder (MDD).

The experimental design consists of three treatment stages and a follow-up phase. Stage I (12 weeks) is a four-group randomized comparison of four treatments: antidepressant medication alone (Fluoxetine); psychotherapy alone (CBT); a combination of the medication and psychotherapy (Comb); and a placebo control medication condition (Pbo). Stage II (six weeks) is a treatment consolidation phase in which we ask whether longer treatment in responders and higher intensity treatment in partial responders to their Stage I treatment would be helpful. Non-responders at the end of Stage I will be referred to open community treatment, or for ethical and practical reasons in the case of non-responders to Placebo, to open treatment of their choice with one of the three active study treatments administered by the study team. Responders at the end of Stage I advance to 6 weeks of maintenance treatment in their assigned arm. Partial responders to CBT receive an additional 6 weeks of CBT in their assigned arm; partial responders to Fluoxetine may receive a higher dose for six weeks. Partial responders to the Comb treatment will receive an additional 6 weeks of CBT and may receive a higher dose of medication for six weeks. Stage III (18 weeks) is a treatment maintenance phase for those teenagers who have continued to respond well. Treatment will be continued and progress will be monitored. Stage IV (one year) is an assessment-only follow-up phase to help us understand the long-term benefits of the treatments.

The recruitment strategy is designed to enter into treatment a volunteer clinical sample of 432 teenagers, both males and females, ages 12 to 17, at ten sites. A multiple gating procedure will be used in which patients will be screened, assessed for study eligibility, and if eligible, consented before randomization to one of the four treatment groups. Patients will be selected without regard to race, gender, or ethnicity and it is expected that the sample will match patients seen in general clinical practice. Patients will be recruited from multiple sources including: mental health identified children, i.e., children already coming to a clinic; primary care identified children (pediatric and family physicians); teacher or school identified children (i.e., school refers through the parents or primary caretaker); and families who self-refer.

Ages Eligible for Study:  12 Years   -   17 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Primary diagnosis DSM-IV of Major Depressive Disorder, pervasive and stable; Children's Depression Rating Scale-R total score at least 45; Ages 12-17 inclusive; Grade in school: 6-12; Full-Scale IQ at least 80; Medication-free before start of study; Outpatient; Parent (or family member) involvement

Exclusion Criteria:

• Bipolar disorder; Severe Conduct Disorder; Substance Use/Abuse/Dependence; Pervasive Developmental Disorders; Thought Disorder; Suicidality or homicidality; Concurrent treatment with psychotropic drug (stable stimulant for ADHD permitted) or psychotherapy outside study; Two previous failed SSRI trials or a failed trial of CBT for depression; Intolerance to fluoxetine; Non-English speaking patient; Pregnancy or breastfeeding; No phone in home; Lack of parent or family member)involvement.

Illinois
      Northwestern University, Chicago,  Illinois,  60611,  United States
Maryland
      Johns Hopkins Hospital, Baltimore,  Maryland,  21287,  United States
Michigan
      Wayne State University, Detroit,  Michigan,  48207,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-5581,  United States
New York
      New York University Medical Center, New York,  New York,  10016,  United States
      New York State Psychiatric Institute, New York,  New York,  10032,  United States
North Carolina
      Behavioral Health Center, Charlotte,  North Carolina,  28203,  United States
Ohio
      Case Western Reserve University, Cleveland,  Ohio,  44106,  United States
      Children's Hospital Medical Center, Cincinnati,  Ohio,  45229,  United States
Oregon
      University of Oregon, Eugene,  Oregon,  97403,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
Texas
      University of Texas Southwestern Medical Center at Dallas, Dallas,  Texas,  75235,  United States

Study chairs or principal investigators

John March,  Study Director,  Duke University   
Anne Marie Albano,  Principal Investigator,  New York University Medical Center   
David Rosenberg, MD,  Principal Investigator,  Wayne State Univ   
Charles Casat,  Principal Investigator,  Carolinas Medical Center-Randlolph   
Graham Emslie,  Principal Investigator,  University of Texas Soutwestern   
Christopher Kratochvil,  Principal Investigator,  University of Nebraska   
Paul Rohde and Anne Simons,  Principal Investigator,  University of Oregon   
John Walkup,  Principal Investigator,  Johns Hopkins University   
Elizabeth Weller,  Principal Investigator,  Children's Hospital of Philadelphia   
Bruce Waslick,  Principal Investigator,  New York State Psychiatric Inst   
Mark Reinecke,  Principal Investigator,  Northwestern University   
Elizabeth Cottingham, MD,  Principal Investigator,  Children's Hospital Medical Center - Cincinnati   
Norah Feeny, PhD,  Principal Investigator,  Case Western Reserve University   

Study ID Numbers:  NO1-MH-80008
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  September 14, 2000
ClinicalTrials.gov Identifier:  NCT00006286
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08