Treatment for Adolescents with Depression Study (TADS): safety results.
OBJECTIVE
To compare the rates of physical, psychiatric, and suicide-related events in adolescents with MDD treated with fluoxetine alone (FLX), cognitive-behavioral therapy (CBT), combination treatment (COMB), or placebo (PBO).


METHODS
Safety assessments included adverse events (AEs) collected by spontaneous report, as well as systematic measures for specific physical and psychiatric symptoms. Suicidal ideation and suicidal behavior were systematically assessed by self- and clinician reports. Suicidal events were also reanalyzed by the Columbia Group and expert raters using the Columbia-Classification Algorithm for Suicidal Assessment used in the U.S. Food and Drug Administration reclassification effort.


RESULTS
Depressed adolescents reported high rates of physical symptoms at baseline, which improved as depression improved. Sedation, insomnia, vomiting, and upper abdominal pain occurred in at least 2% of those treated with FLX and/or COMB and at twice the rate of placebo. The rate of psychiatric AEs was 11% in FLX, 5.6% in COMB, 4.5% in PBO, and 0.9% in CBT. Suicidal ideation improved overall, with greatest improvement in COMB. Twenty-four suicide-related events occurred during the 12-week period: 5 patients (4.7%) in COMB, 10 (9.2%) in FLX, 5 (4.5%) in CBT, and 3 (2.7%) in placebo. Statistically, only FLX had more suicide-related events than PBO (p =.0402, odds ratio (OR) = 3.7, 95% CI 1.00-63.7). Only five actual attempts occurred (2 COMB, 2 FLX, 1 CBT, 0 PBO). There were no suicide completions.


CONCLUSIONS
Different methods for eliciting AEs produce different results. In general, as depression improves, physical complaints and suicidal ideation decrease in proportion to treatment benefit. In this study, psychiatric AEs and suicide-related events are more common in FLX-treated patients. COMB treatment may offer a more favorable safety profile than medication alone in adolescent depression.
Emslie
Graham
G
UT Southwestern Medical Centre at Dallas, TX 75390-8589, USA. emslie@utsouthwestern.edu
Kratochvil
Christopher
C
Vitiello
Benedetto
B
Silva
Susan
S
Mayes
Taryn
T
McNulty
Steven
S
Weller
Elizabeth
E
Waslick
Bruce
B
Casat
Charles
C
Walkup
John
J
Pathak
Sanjeev
S
Rohde
Paul
P
Posner
Kelly
K
March
John
J
D000293:Adolescent; D000465:Algorithms; D002648:Child; D015928:Cognitive Behavioral Therapy / Q000379:methods*; 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 / Q000627:therapeutic use*; D006801:Humans; D008016:Life Change Events; D008297:Male; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data; D011795:Surveys and Questionnaires
D005473:Fluoxetine