Assessment of safety and long-term outcomes of initial treatment with placebo in TADS.
OBJECTIVE
The authors examined whether initial assignment to receive placebo for 12 weeks followed by open active treatment as clinically indicated was associated with different levels of benefit and risk of harm across 36 weeks as compared with initial assignment to receive active treatments.


METHODS
Adolescents with major depressive disorder (N=439) were randomly assigned to receive an initial 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy (CBT), combination treatment with fluoxetine and CBT, or clinical management with placebo; those assigned to placebo received open active treatment as clinically indicated after 12 weeks of placebo. Assessments were conducted every 6 weeks for 36 weeks. The primary outcome measures were response and remission based on scores on the Children's Depression Rating Scale-Revised and the Clinical Global Impression improvement subscale.


RESULTS
At week 36, the response rate was 82% in the placebo/open group and 83% in the active treatment groups. The remission rate was 48% in the placebo/open group and 59% in the active treatment groups, a difference that approached statistical significance. Patients who responded to placebo generally retained their response. Those who did not respond to placebo subsequently responded to active treatment at the same rate as those initially assigned to active treatments. There were no differences between groups in rates of suicidal events, study retention, or symptom worsening.


CONCLUSIONS
Remission rates at 9 months were lower in patients treated initially with placebo, but 3 months of placebo treatment was not associated with any harm or diminished response to subsequent treatment.
Kennard
Betsy D
BD
University of Texas Southwestern Medical Center at Dallas, 75390-8589, USA. beth.kennard@utsouthwestern.edu
Silva
Susan G
SG
Mayes
Taryn L
TL
Rohde
Paul
P
Hughes
Jennifer L
JL
Vitiello
Benedetto
B
Kratochvil
Christopher J
CJ
Curry
John F
JF
Emslie
Graham J
GJ
Reinecke
Mark A
MA
March
John S
JS
D000293:Adolescent; D002648:Child; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000628:therapy*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors