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

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

429 patients Age 12 -17 years (mean age 15 years) Primary diagnosis of major depressive

disorder (DSM-IV)

Inclusion Criteria

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

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

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

Blinding Independent evaluators

Fluoxetine

6 medication visits x 20-30 minutes Dosage adjusted

Starting dose 10 mg/d Optimum 20 mg/d Maximum 40 mg/d

Mean highest dose 30 mg/d

CBT

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

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

Reynolds Adolescent Depression Scale (RADS)

Suicidal Ideation Questionnaire-Junior High School Version (SIQ-Jr)

All measures reported acceptable psychometric properties

Harm-Related Adverse Event

Harm to self; e.g. cutting Worsening of suicidal ideation Suicidal attempt Harm to others

Suicide-Related Adverse Event

Worsening suicidal ideation Suicidal attempt

Results

Combination of fluoxetine with CBT was significantly superior to placebo fluoxetine alone CBT alone

Results

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

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

0.980.843

Fluoxetine alone

0.680.584

CBT alone-0.030.2012

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

Suicidal ideation decreased in all of the treatment groups

6% of the patients experienced a suicide-related 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

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

Combination treatment with fluoxetine and CBT shows highest efficacy

CBT is a protective factor for suicide in adolescents receiving fluoxetine