Transcript Treatment for Adolescents With Depression Study (TADS)

Treatment for
Adolescents With
Depression Study
(TADS)
Fluoxetine, Cognitive Behavioral
Therapy, and Their Combination for
Adolescents With Depression
Treatment for Adolescents With Depression
Study (TADS) Team
JAMA 2004: Vol 292, No. 7
TADS
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A randomized controlled trial funded by the
National Institute of Mental Health
Conducted at 13 academic and community
centers in the United States
To evaluate the effectiveness of treatments
for adolescents with MDD
Participants
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429 patients
Age 12 -17 years (mean age 15 years)
Primary diagnosis of major depressive
disorder (DSM-IV)
Inclusion Criteria
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Outpatient
CDRS ≥ 45
IQ ≥ 80
Not taking antidepressants
Depressive mood in at least 2 contexts for at
least 6 weeks prior to consent
Exclusion criteria
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Bipolar disorder
Severe conduct disorder
Substance abuse
PDD
Thought disorder
Concurrent psychotropic medications
Failed 2 SSRIs or CBT
Exclusion criteria
Dangerousness to self or others
 Had been hospitalized for dangerousness
within 3 months
 Suicidal attempt within 6 months
 Active plan of suicide
 Suicidal ideation with disorganized family
Participants
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Moderate to severe symptoms
Average depressive episode duration - 72
weeks
27% had at least minimal suicidal ideation at
baseline
Randomization
To 1 of 4 treatments for 12 weeks
1. Fluoxetine alone
2. CBT alone
3. Fluoxetine with CBT
4. Placebo
Randomization
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Blinding
Independent evaluators
Fluoxetine
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6 medication visits x 20-30 minutes
Dosage adjusted
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Starting dose 10 mg/d
Optimum 20 mg/d
Maximum 40 mg/d
Mean highest dose 30 mg/d
CBT
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15 sessions over 12 weeks x 50-60 minutes
Psychoeducation
Mood monitoring
Increasing pleasant activities
Social problem solving
Cognitive restructuring
Parent and family sessions
Outcome Assessment
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Children’s Depression Rating Scale-Revised
(CDRS-R)
CGI improvement score (much improved or
very much improved)
Assessed at baseline, week 6, and week12
Outcome Assessment
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Reynolds Adolescent Depression Scale
(RADS)
Suicidal Ideation Questionnaire-Junior High
School Version (SIQ-Jr)
All measures reported acceptable
psychometric properties
Harm-Related Adverse Event
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Harm to self; e.g. cutting
Worsening of suicidal ideation
Suicidal attempt
Harm to others
Suicide-Related Adverse Event
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Worsening suicidal ideation
Suicidal attempt
Results
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Combination of fluoxetine with CBT was
significantly superior to
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placebo
fluoxetine alone
CBT alone
Results
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Fluoxetine alone was superior to placebo
CBT alone was not superior to placebo
Fluoxetine alone was significantly better than
CBT alone
Response Rate Based On CGI
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71% in the fluoxetine with CBT
61% in the fluoxetine alone
43% in the CBT alone
35% in the placebo
Results
Effect size
(CDRS-R)
Effect size
(CGI)
NNT
Fluoxetine
+ CBT
0.98
0.84
3
Fluoxetine
alone
0.68
0.58
4
CBT alone
-0.03
0.20
12
Results
“Combination of fluoxetine with CBT is better
than fluoxetine alone, which is better than
CBT alone, which is equal to placebo”
Suicidal Behavior in Children
Receiving SSRIs
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Suicidal ideation decreased in all of the
treatment groups
6% of the patients experienced a suiciderelated event with no statistically significant
difference among the 4 treatment groups
Seven patients made a suicide attempt and
there were no completed suicides
Suicidal Behavior in Children
Receiving SSRIs
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Harm-related adverse events: increased risk
(odds ratio = 2.19) for patients receiving
fluoxetine compared with those who were not
The odds ratio was higher for fluoxetine alone
compared with fluoxetine with CBT.
Protective effect for CBT for suicidal ideation
Summary
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Combination treatment with fluoxetine and
CBT shows highest efficacy
CBT is a protective factor for suicide in
adolescents receiving fluoxetine