The Treatment for Adolescents With Depression Study (TADS): long-term effectiveness and safety outcomes.
BACKGROUND
The Treatment for Adolescents With Depression Study evaluates the effectiveness of fluoxetine hydrochloride therapy, cognitive behavior therapy (CBT), and their combination in adolescents with major depressive disorder.


OBJECTIVE
To report effectiveness outcomes across 36 weeks of randomized treatment.


METHODS
Randomized, controlled trial conducted in 13 academic and community sites in the United States. Cognitive behavior and combination therapies were not masked, whereas administration of placebo and fluoxetine was double-blind through 12 weeks, after which treatments were unblinded. Patients assigned to placebo were treated openly after week 12, and the placebo group is not included in these analyses by design.


METHODS
Three hundred twenty-seven patients aged 12 to 17 years with a primary DSM-IV diagnosis of major depressive disorder.


METHODS
All treatments were administered per protocol.


METHODS
The primary dependent measures rated blind to treatment status by an independent evaluator were the Children's Depression Rating Scale-Revised total score and the response rate, defined as a Clinical Global Impressions-Improvement score of much or very much improved.


RESULTS
Intention-to-treat analyses on the Children's Depression Rating Scale-Revised identified a significant time x treatment interaction (P < .001). Rates of response were 73% for combination therapy, 62% for fluoxetine therapy, and 48% for CBT at week 12; 85% for combination therapy, 69% for fluoxetine therapy, and 65% for CBT at week 18; and 86% for combination therapy, 81% for fluoxetine therapy, and 81% for CBT at week 36. Suicidal ideation decreased with treatment, but less so with fluoxetine therapy than with combination therapy or CBT. Suicidal events were more common in patients receiving fluoxetine therapy (14.7%) than combination therapy (8.4%) or CBT (6.3%).


CONCLUSIONS
In adolescents with moderate to severe depression, treatment with fluoxetine alone or in combination with CBT accelerates the response. Adding CBT to medication enhances the safety of medication. Taking benefits and harms into account, combined treatment appears superior to either monotherapy as a treatment for major depression in adolescents.
March
John S
JS
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA. jsmarch@duke.edu
Silva
Susan
S
Petrycki
Stephen
S
Curry
John
J
Wells
Karen
K
Fairbank
John
J
Burns
Barbara
B
Domino
Marisa
M
McNulty
Steven
S
Vitiello
Benedetto
B
Severe
Joanne
J
D000293:Adolescent; D002985:Clinical Protocols; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010919:Placebos; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013405:Suicide / Q000523:psychology; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D000092864:Suicide Prevention
D005473:Fluoxetine; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors