The Treatment for Adolescents with Depression Study (TADS)
The Treatment for Adolescents with Depression Study (TADS)
Definition
The Treatment for Adolescents with Depression Study (TADS) was a clinical trial sponsored by the National Institutes of Health that examined the effectiveness of short- and long-term medication and psychotherapy treatments for teenagers (aged 12-17) with major depressive disorder (MDD).
MDD is a mood disorder also known as major depression, clinical depression, or unipolar depression. A person with MDD has experienced at least five of the nine symptoms below for two weeks or more, for most of the time almost every day, and this is a change from their prior level of functioning. One of the symptoms must be either (a) depressed mood, or (b) loss of interest. Recurrent MDD is diagnosed when two or more of these depressive periods occur with at least two months between episodes.
- Depressed mood (may be manifested as irritable mood).
- A significantly reduced level of interest or pleasure in most or all activities.
- A considerable loss or gain of weight (may also be an increase or decrease in appetite).
- Difficulty falling or staying asleep (insomnia), or sleeping more than usual (hypers omnia).
- Behavior that is agitated or slowed down (observable by others).
- Feeling fatigued, or having diminished energy.
- Thoughts of worthlessness or extreme guilt (not about being ill).
- Ability to think, concentrate, or make decisions is reduced.
- Frequent thoughts of death or suicide (with or without a specific plan), or suicide attempt.
It is estimated that 3 to 5% of adolescents in the United States have MDD. Depression occurs both in boys and in girls, although it is more prevalent in girls, and it is one of the most common disorders of adolescence. MDD frequently interferes with home, school, and family life, and often causes a high degree of family stress. Suicide is the third leading cause of death among teenagers, with approximately 50% of the deaths associated with depression.
Description
TADS was conducted at 13 academic and community clinics across the United States and enrolled 439 participants. The first participant entered TADS in the spring of 2000 and the last one in the summer of 2003. The initial findings were gathered from data from the first 12-week treatment period. The study showed that the antidepressant fluoxetine and cognitive behavioral therapy combined produced the best success rate in treating depression in adolescents; 71% of participants receiving both medication and cognitive behavioral therapy improved at the end of 12 weeks of treatment. Medication alone was also an effective treatment; 61% of participants improved; cognitive behavioral therapy alone improved 44% of the cases; and 35% percent of the subjects improved with clinical management and placebo combined. Cognitive behavioral therapy taught the adolescent participant and their family skills to help relieve the depression.
TADS participants were randomly assigned to four treatment arms: 1) fluoxetine medication alone, 2) clinical management with placebo, 3) cognitive behavior therapy (CBT, talking with a therapist), and 4) combination of medication and CBT. The treatment phase was conducted in stages. Stage I lasted 12 weeks and included 6–14 visits to the clinic.
At the end of the first 12-week stage participants were advised of the treatment group to which they were assigned. Participants in the placebo group 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 (6 weeks, 2–6 clinic visits) and stage III (18 weeks, 3 clinic visits) participants received one of three treatments: 1) fluoxetine alone, 2) CBT
alone, or 3) fluoxetine with CBT. Only participants who responded to one of the active treatments in stage I continued with treatment in stages II and III. Participants who responded well in stage I continued with their original treatment in stage II and later in stage III.
Fluoxetine is the generic name for Prozac, a selective serotonin reuptake inhibitor (SSRI). SSRIs primarily affect serotonin, a neurotransmitter in the brain that plays a pivotal role in depression. Neurotransmitters modulate mood, emotion, sleep, and appetite. Fluoxetine is the only medication approved by the FDA to treat depression in adolescents. However, since the TADS study, more recent studies suggest that antidepressant use in adolescents may be associated with a higher incidence of suicidal behavior and suggest close observation and caution.
CBT is a form of psychotherapy that emphasizes modifying everyday thoughts and behaviors, with the aim of positively influencing emotions. The precise therapeutic techniques vary according to particular client and issue, but commonly include keeping a diary of significant events and associated feelings, thoughts, and behaviors; questioning and testing assumptions or habits of thoughts that might be unhelpful and unrealistic; gradually facing activities that may have been avoided; and trying out new ways of behaving and reacting. Relaxation and distraction techniques are also commonly used.
Results
The study determined that the combination of fluoxetine with CBT was significantly better than fluoxetine alone or CBT alone in treating the symptoms of depression in adolescents. Fluoxetine alone was found to be a superior treatment to CBT alone. Clinically significant suicidal thinking, which was present in 29% of the sample at the beginning of the study, while improved significantly in all four treatment arms, was most improved in the fluoxetine with CBT group. The data suggest that the combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with MDD.
Resources
BOOK
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text rev. Washington D.C.: American Psychiatric Association, 2000.
PERIODICALS
Bhatia, S. K., and S. C. Bhatia. “Childhood and Adolescent Depression.” American Family Physician 75.1 (2007): 73–80.
Emslie, G., and others. Columbia Suicidality Classification Group; TADS Team. “Treatment for Adolescents with Depression Study (TADS): Safety Results.” Journal of the American Academy of Child and Adolescent Psychiatry 45.12 (2006):1440–55.
March, J., S. Silva, and B. Vitiello. TADS Team. “The Treatment for Adolescents with Depression Study (TADS): Methods and Message at 12 Weeks.” Journal of the American Academy of Child and Adolescent Psychiatry 45.12 (2006): 1393–1403.
Simon, G. E. “The Antidepressant Quandary: Considering Suicide Risk when Treating Adolescent Depression.” New England Journal of Medicine 355.26 (2006): 2722–23.
Vitiello, B., and others. TADS Team. “Functioning and Quality of Life in the Treatment for Adolescents with Depression Study (TADS).” Journal of the American Academy of Child and Adolescent Psychiatry 45.2 (2006): 1419–26.
ORGANIZATION
National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892. Telephone: (301) 496-4000. Web site: http://www.nih.gov
Andrew J. Bean, PhD