NIMH releases clinical research on medication and psychotherapy for treating depression in adolescents (TADS)
- What is TADS?
- Who sponsored this study?
- What do the results of the study mean for children who have depression?
- How can results of TADS be generalized?
- What treatments were used?
- What happened during the treatment phase of the study?
- What happened during the follow-up period?
- Will there be additional studies on the efficacy of using other antidepressants for depression in adolescents?
- Do the pros outweigh the cons for adolescents using an antidepressant?
- What is fluoxetine?
- Is fluoxetine approved by the FDA?
- What is cognitive-behavioral therapy?
- What is a placebo?
- What is a clinical trial?
- Who was eligible for TADS?
- How many children and adolescents have depression?
- Was compensation provided for participation?
Q. What is TADS?
A. The Treatment for
Adolescents with Depression Study (TADS) was a multi-site clinical research
study comparing short- and longer-term effectiveness of medication and psychotherapy
for depression in adolescents aged 12 to 17. Thirteen academic and
community clinics across the country were involved in the $17 million federally
funded, peer reviewed and monitored clinical research study. For the 439 participants
studied in TADS, the trial was designed to test best-practice care for depression,
also known as Major Depressive Disorder (MDD). The first participant entered
TADS in spring 2000 and the last one in the summer 2003.
The initial findings published in the August 18, 2004, issue of the Journal
of the American Medical Association (JAMA), provide data from the first
12-week treatment period. Additional reports will be available as data from
the remainder of the study are collected and reviewed.
Q. Who sponsored this study?
A. TADS was sponsored by the National Institute of Mental Health (NIMH)
and coordinated by the Department of Psychiatry and the Duke Clinical Research
Institute at Duke University Medical Center. The principal investigator for
the study was John March, M.D., MPH; the principal statistician was Susan Silva,
Ph.D., both at Duke University. NIMH is part of the National Institutes of Health
(NIH), the Federal Government's primary agency for biomedical and behavioral
research. NIH is a component of the U.S. Department of Health and Human Services.
Eli Lilly provided the drug and matching placebo to Duke as an independent
educational grant. Eli Lilly had no role in the design or implementation of
the study, analysis of the data, or writing of the manuscript.
Q. What do the results of the study mean for children
who have depression?
A. The TADS study showed that fluoxetine and cognitive-behavioral
therapy combined produced the best success rate in treating depression in adolescents;
71 percent of participants receiving both medication and talk therapy improved
at the end of 12 weeks of treatment. Medication alone was also an effective
treatment; 61 percent of participants improved; cognitive-behavioral therapy
alone improved 44 percent of the cases; and clinical management with placebo,
35 percent (on the latter two, the difference is not statistically significant).
The placebo condition helped scientists determine to what extent the active
treatments improved adolescent depression compared to an inactive treatment.
Cognitive-behavioral therapy, which was used to treat depression, taught the
adolescent participant and family new skills to cope with and then relieve the
depression. The combination of medication and cognitive-behavioral therapy allowed
researchers to evaluate the relative benefits of combining the two treatments
when treating depressed adolescents.
Q. How can results of TADS be generalized?
A. The results of TADS apply to the treatments that were tested
in this study, that is fluoxetine (Prozac®) and cognitive-behavioral therapy
Q. What Treatments Were Used?
A. There were four treatment conditions to which TADS participants
were randomly assigned. These treatments were:
Fluoxetine - medication alone
Clinical management with placebo (inert pill) - alone
Cognitive-behavior therapy (CBT) - talking with a therapist
Combination of both medication and CBT
At the time the TADS study was launched, the Food and Drug Administration
(FDA) had approved fluoxetine for use in the treatment of adult depression.
During the course of the study, FDA extended approved use of fluoxetine to include
treatment of adolescents. Generic versions of the drug became available to consumers
Q. What happened during the treatment phase of the study?
A. The 9-month treatment phase was conducted in stages. Stage
I lasted 12 weeks and included 6-14 visits to the clinic. Participants were
randomly assigned to one of four treatments—active medication alone, placebo
alone, CBT alone, or active medication and CBT.
At the end of the first 12-week stage researchers told the participant, family
and doctors which pill the participant took—placebo or active medication. Participants
taking the placebo who did not improve during the first 12 weeks, or whose depression
returned within 3 months, were offered any one of the other three treatments
in the study—active medication, CBT, or both.
The placebo condition was used only in Stage I. During Stages II and III participants
received one of three treatment groups - fluoxetine alone, CBT alone, and fluoxetine
with CBT. Only participants who responded to one of the active treatments in
Stage I continued with treatment in Stages II and III. Stage II took 6 weeks
and involved two to six visits to the clinic. Participants who responded well
in Stage II continued with their original treatment in Stage II and later in
Stage III lasted 18 weeks and included three clinic visits. If a participant?s
depression worsened or did not improve, the doctor talked with the family about
other treatment options.
Q. What happened during the follow-up period?
A. During the one year follow-up period, participants came
to the clinic four times at 3, 6, 9, and 12 months following the end of the
treatment period. These visits were called "assessments" and consisted
of interviews and questionnaires similar to those administered at the beginning
of the study.
Because the study did not provide treatment during the follow-up period, the
TADS doctors met with the family when needed or requested to discuss recommendations
for treatment options in the community.
Q. Will there be additional studies on the efficacy
of using other antidepressants for depression in adolescents?
A. NIMH is currently funding other studies involving adolescents
with depression including Treatment
of Resistant Depression in Adolescents (TORDIA) and Treatment
of Adolescent Suicide Attempters (TASA). For a complete list of all NIMH
clinical trials and for information about these two in particular, please visit
http://www.nimh.nih.gov/studies/index.cfm or clinicaltrials.gov.
Q. Do the pros outweigh the cons for adolescents using
A. The data from TADS indicate that there is a favorable balance
between risk and benefits for the use of fluoxetine in the treatment of adolescents
with depression, especially when this medication is used in conjunction with
cognitive-behavioral therapy. However, decisions about treatment for adolescents
with depression must be made on a case-by-case basis involving their parents
and their doctors.
Before starting treatment, each child should be carefully and thoroughly evaluated
by a physician to determine if medication is appropriate. Those who are prescribed
an SSRI should receive ongoing monitoring by a health care professional, especially
during the first few days. For more information about treatment of depression
in adolescents, visit the NIMH website at http://www.nimh.nih.gov/HealthInformation/depchildmenu.cfm.
Q. What is fluoxetine?
A. Fluoxetine is the generic name for Prozac®, a member of
the medication class called selective serotonin reuptake inhibitors (SSRI).
Medications in this class primarily affect the neurotransmitter serotonin, one
of the chemicals in the brain that play a role in depression and to modulate
mood, emotion, sleep and appetite. 1Generic versions
of the drug became available to consumers in 2001.
Q. Is fluoxetine approved by the FDA?
A. Fluoxetine is the only medication approved by the FDA to
treat depression in adolescents.
Q. What is cognitive-behavioral therapy?
A. Cognitive-behavioral therapy (CBT) is a talking therapy
that teaches the patient new skills to cope better with depression. Specific
topics may 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. 2
Q. What is a placebo?
A. A placebo is made of material without pharmacological
activity but is presented to be identical in appearance to an active drug. Placebos
are used in clinical pharmacological research to allow comparisons and determine
the actual effects of the drug being tested.3
Q. What is a clinical trial?
A. A clinical trial is a clinical research study in human
volunteers to answer specific questions. Carefully conducted clinical trials
are the gold standard to study treatments that work in people.
Q. Who was eligible for TADS?
A. TADS recruited participants, between 12-17 years of age,
who at the time of recruitment were experiencing symptoms of depression. At
least one parent was required to participate in order to collect information
and supervise treatment at home. Other criteria were based on such factors as
age, gender, the type and stage of a disease, previous treatment history, and
other medical conditions.4 Inclusion and
exclusion criteria were used to identify appropriate participants and keep them
Q. How many children and adolescents have depression?
A. Experts estimate that in the United States, 1 in 20 teens,
or five percent, have moderately severe to severe major depression. This means
that in a high school of 1,000 adolescents, 50 would be likely to have a significant
major depressive episode on any given day.5 Depression
occurs both in boys and in girls. Major depression is one of the most common
disorders of adolescence. A substantial number of depressed adolescents, but
by no means all, have suicidal thoughts. Without effective treatment some will
eventually commit suicide.
Q. Was compensation provided for participation?
A. Families received $100 for each major assessment completed.
An additional $10 was provided at each visit to cover travel and parking costs.
The medical evaluation, study medication, and/or treatment sessions that were
provided free of charge to the participants.
1 Medications, Revised.
NIMH, Department of Health and Human Services. 2002.
3 American Psychiatric Glossary,
7th Edition, American Psychiatric Press, Inc. ed. Jane E. Edgerton
and Robert J. Campbell III, M.D., Washington, DC 1994.
5 Essau C, Dobson K. Epidemiology
of depressive disorders. In: Essau C, Petermann F, eds. Depressive Disorders
in Children and Adolescents: Epidemiology, Course and Treatment. Northvale,
NJ: Jason Aronson Inc; 1999:69-103.
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