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1.
Essau  CDobson  K Epidemiology of depressive disorders. Essau  CPetermann  Feds Depressive Disorders in Children and Adolescents: Epidemiology, Course and Treatment. Northvale, NJ Jason Aronson, Inc1999;69- 103Google Scholar
2.
Angold  AMesser  SCStangl  DFarmer  EMCostello  EJBurns  BJ Perceived parental burden and service use for child and adolescent psychiatric disorders.  Am J Public Health 1998;88 (1) 75- 80PubMedGoogle Scholar
3.
Shaffer  DGould  MSFisher  PTrautman  PMoreau  DKleinman  MFlory  M Psychiatric diagnosis in child and adolescent suicide.  Arch Gen Psychiatry 1996;53 (4) 339- 348PubMedGoogle Scholar
4.
Gould  MSKing  RGreenwald  SFisher  PSchwab-Stone  MKramer  RFlisher  AJGoodman  SCanino  GShaffer  D Psychopathology associated with suicidal ideation and attempts among children and adolescents.  J Am Acad Child Adolesc Psychiatry 1998;37 (9) 915- 923PubMedGoogle Scholar
5.
Treatment for Adolescents With Depression Study Team, Treatment for Adolescents With Depression Study (TADS): rationale, design, and methods.  J Am Acad Child Adolesc Psychiatry 2003;42 (5) 531- 542PubMedGoogle Scholar
6.
Treatment for Adolescents With Depression Study Team, The Treatment for Adolescents With Depression Study (TADS): demographic and clinical characteristics.  J Am Acad Child Adolesc Psychiatry 2005;44 (1) 28- 40PubMedGoogle Scholar
7.
March  JSilva  SPetrycki  SCurry  JWells  KFairbank  JBurns  BDomino  MMcNulty  SVitiello  BSevere  JTreatment for Adolescents With Depression Study (TADS) Team, Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial.  JAMA 2004;292 (7) 807- 820PubMedGoogle Scholar
8.
Hammad  TALaughren  TRacoosin  J Suicidality in pediatric patients treated with antidepressant drugs.  Arch Gen Psychiatry 2006;63 (3) 332- 339PubMedGoogle Scholar
9.
Emslie  GKratochvil  CVitiello  BSilva  SMayes  TMcNulty  SWeller  EWaslick  BCasat  CWalkup  JPathak  SRohde  PPosner  KMarch  JColumbia Suicidality Classification Group, TADS Team. Treatment for Adolescents with Depression Study: safety results.  J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1440- 1455PubMedGoogle Scholar
10.
Vitiello  BSwedo  S Antidepressant medications in children.  N Engl J Med 2004;350 (15) 1489- 1491PubMedGoogle Scholar
11.
Curry  JFWells  KC Striving for effectiveness in the treatment of adolescent depression: cognitive behavior therapy for multisite community intervention.  Cogn Behav Pract 2005;12 (2) 177- 185Google Scholar
12.
Ginsburg  GSAlbano  AMFindling  RLKratochvil  CWalkup  J Integrating cognitive behavioral therapy and pharmacotherapy in the treatment of adolescent depression.  Cogn Behav Pract 2005;12 (2) 252- 262Google Scholar
13.
Kennard  BDGinsburg  GSFeeny  NCSweeney  MZagurski  R Implementation challenges to TADS cognitive-behavioral therapy.  Cogn Behav Pract 2005;12 (2) 230- 239Google Scholar
14.
Kratochvil  CJSimons  AVitiello  BWalkup  JEmslie  GRosenberg  DMarch  JS A multisite psychotherapy and medication trial for depressed adolescents: background and benefits.  Cogn Behav Pract 2005;12 (2) 159- 16510.1016/S1077-7229(05)80021-5Google Scholar
15.
Rogers  GMReinecke  MACurry  JF Case formulation in TADS CBT.  Cogn Behav Pract 2005;12 (2) 198- 208Google Scholar
16.
Rohde  PFeeny  NCRobins  M Characteristics and components of the TADS CBT approach.  Cogn Behav Pract 2005;12 (2) 186- 197PubMedGoogle Scholar
17.
Simons  ADRohde  PKennard  BDRobins  M Relapse and recurrence prevention in the Treatment for Adolescents With Depression Study.  Cogn Behav Pract 2005;12 (2) 240- 251Google Scholar
18.
Sweeney  MRobins  MRuberu  MJones  J African-American and Latino families in TADS: recruitment and treatment considerations.  Cogn Behav Pract 2005;12 (2) 221- 229Google Scholar
19.
Poznanski  EMokros  H Children's Depression Rating Scale–Revised (CDRS-R).  Los Angeles, CA WPS1995;
20.
Guy  W ECDEU Assessment Manual for Psychopharmacology. 2nd Washington, DC Dept of Health Education and Welfare1976;DHEW publication (ABM)76- 388
21.
Reynolds  WM Professional Manual for the Reynolds Adolescent Depression Scale.  Odessa, FL Psychological Assessment Resources Inc1987;
22.
Reinecke  MARyan  NEDuBois  DL Cognitive-behavioral therapy of depression and depressive symptoms during adolescence: a review and meta-analysis.  J Am Acad Child Adolesc Psychiatry 1998;37 (1) 26- 34PubMedGoogle Scholar
23.
Reynolds  WM Professional Manual for the Suicidal Ideation Questionnaire.  Odessa, FL Psychological Assessment Resources Inc1987;
24.
Brown  HPrescott  R Applied Mixed Models in Medicine.  New York, NY John Wiley & Sons Inc1999;
25.
Koch  GGGansky  SA Statistical considerations for multiplicity in confirmatory protocols.  Drug Inf J 1996;30523- 534Google Scholar
26.
Rosenthal  RRosnow  RRubin  DB Contrasts and Effect Sizes in Behavioral Research.  New York, NY Cambridge University Press2000;
27.
Sackett  DRichardson  WRosenberg  WHaynes  B Evidence-Based Medicine. 2nd New York, NY Churchill Livingston Inc2000;
28.
Jensen  PS NIMH's TADS: more than just a tad of progress?  Cogn Behav Pract 2005;12 (2) 156- 158Google Scholar
29.
Kennard  BSilva  SVitiello  BCurry  JKratochvil  CSimons  AHughes  JFeeny  NWeller  ESweeney  MReinecke  MPathak  SGinsburg  GEmslie  GMarch  J TADS Team. Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with Depression Study (TADS).  J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1404- 1411PubMedGoogle Scholar
30.
Vitiello  BRohde  PSilva  SWells  KCasat  CWaslick  BSimons  AReinecke  MWeller  EKratochvil  CWalkup  JPathak  SRobins  MMarch  J TADS Team. Functioning and quality of life in the Treatment for Adolescents With Depression Study (TADS).  J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1419- 1426PubMedGoogle Scholar
31.
March  JSilva  SVitiello  B TADS Team. The Treatment for Adolescents With Depression Study (TADS): methods and message at 12 weeks.  J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1393- 1403PubMedGoogle Scholar
32.
Melvin  GATonge  BJKing  NJHeyne  DGordon  MSKlimkeit  E A comparison of cognitive-behavioral therapy, sertraline, and their combination for adolescent depression.  J Am Acad Child Adolesc Psychiatry 2006;45 (10) 1151- 1161PubMedGoogle Scholar
33.
Clarke  GDebar  LLynch  FPowell  JGale  JO’Connor  ELudman  EBush  TLin  EHVon Korff  MHertert  S A randomized effectiveness trial of brief cognitive-behavioral therapy for depressed adolescents receiving antidepressant medication.  J Am Acad Child Adolesc Psychiatry 2005;44 (9) 888- 898PubMedGoogle Scholar
34.
Curry  JRohde  PSimons  ASilva  SVitiello  BKratochvil  CReinecke  MFeeny  NWells  KPathak  SWeller  ERosenberg  DKennard  BRobins  MGinsburg  GMarch  J Predictors and moderators of acute treatment outcome in the Treatment for Adolescents With Depression Study (TADS).  J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1427- 1439PubMedGoogle Scholar
35.
Compton  SNMarch  JSBrent  DAlbano  AMWeersing  RCurry  J Cognitive-behavioral psychotherapy for anxiety and depressive disorders in children and adolescents: an evidence-based medicine review.  J Am Acad Child Adolesc Psychiatry 2004;43 (8) 930- 959PubMedGoogle Scholar
36.
Whittington  CJKendall  TFonagy  PCottrell  DCotgrove  ABoddington  E Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data.  Lancet 2004;363 (9418) 1341- 1345PubMedGoogle Scholar
37.
Emslie  GJMayes  TLRuberu  M Continuation and maintenance therapy of early-onset major depressive disorder.  Paediatr Drugs 2005;7 (4) 203- 217PubMedGoogle Scholar
38.
Hollon  SDGarber  JShelton  RC Treatment of depression in adolescents with cognitive behavior therapy and medications: a commentary on the TADS project.  Cogn Behav Pract 2005;12 (2) 149- 155Google Scholar
39.
Hollon  SDDeRubeis  RJShelton  RCAmsterdam  JDSalomon  RMO’Reardon  JPLovett  MLYoung  PRHaman  KLFreeman  BBGallop  R Prevention of relapse following cognitive therapy vs medications in moderate to severe depression.  Arch Gen Psychiatry 2005;62 (4) 417- 422PubMedGoogle Scholar
40.
Hollon  SDJarrett  RBNierenberg  AAThase  METrivedi  MRush  AJ Psychotherapy and medication in the treatment of adult and geriatric depression: which monotherapy or combined treatment?  J Clin Psychiatry 2005;66 (4) 455- 468PubMedGoogle Scholar
41.
Weisz  JRMcCarty  CAValeri  SM Effects of psychotherapy for depression in children and adolescents: a meta-analysis.  Psychol Bull 2006;132 (1) 132- 149PubMedGoogle Scholar
42.
Jureidini  JNDoecke  CJMansfield  PRHaby  MMMenkes  DBTonkin  AL Efficacy and safety of antidepressants for children and adolescents.  BMJ 2004;328 (7444) 879- 883PubMedGoogle Scholar
43.
Jureidini  JTonkin  AMansfield  PR TADS study raises concerns.  BMJ 2004;329 (7478) 1343- 1344Google Scholar
44.
Glass  RM Treatment of adolescents with major depression: contributions of a major trial.  JAMA 2004;292 (7) 861- 863PubMedGoogle Scholar
45.
Apter  AKronenberg  SBrent  D Turning darkness into light: a new landmark study on the treatment of adolescent depression: comments on the TADS study.  Eur Child Adolesc Psychiatry 2005;14 (3) 113- 116PubMedGoogle Scholar
46.
Kratochvil  CEmslie  GSliva  SMcNulty  SWalkup  JCurry  JReinecke  MVitiello  BRohde  PFeeny  NCasat  CPathak  SWeller  EMay  DMayes  TRobins  MMarch  J Acute time to response in the Treatment for Adolescents with Depression Study (TADS).  J Am Acad Child Adolesc Psychiatry 2006;45 (12) 1412- 1418PubMedGoogle Scholar
47.
Emslie  GJRush  AJWeinberg  WAKowatch  RAHughes  CWCarmody  TRintelmann  J A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression.  Arch Gen Psychiatry 1997;54 (11) 1031- 1037PubMedGoogle Scholar
48.
Emslie  GJHeiligenstein  JHWagner  KDHoog  SLErnest  DEBrown  ENilsson  MJacobson  JG Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial.  J Am Acad Child Adolesc Psychiatry 2002;41 (10) 1205- 1215PubMedGoogle Scholar
49.
Negron  RPiacentini  JGraae  FDavies  MShaffer  D Microanalysis of adolescent suicide attempters and ideators during the acute suicidal episode.  J Am Acad Child Adolesc Psychiatry 1997;36 (11) 1512- 1519PubMedGoogle Scholar
50.
March  JKratochvil  CClarke  GBeardslee  WDerivan  AEmslie  GGreen  EPHeiligenstein  JHinshaw  SHoagwood  KJensen  PLavori  PLeonard  HMcNulty  JMichaels  MAMossholder  AOsher  TPetti  TPrentice  EVitiello  BWells   AACAP 2002 research forum: placebo and alternatives to placebo in randomized controlled trials in pediatric psychopharmacology.  J Am Acad Child Adolesc Psychiatry 2004;43 (8) 1046- 1056PubMedGoogle Scholar
51.
Birmaher  BArbelaez  CBrent  D Course and outcome of child and adolescent major depressive disorder.  Child Adolesc Psychiatr Clin N Am 2002;11 (3) 619- 637, xPubMedGoogle Scholar
52.
Birmaher  BBrent  DAKolko  DBaugher  MBridge  JHolder  DIyengar  SUlloa  RE Clinical outcome after short-term psychotherapy for adolescents with major depressive disorder.  Arch Gen Psychiatry 2000;57 (1) 29- 36PubMedGoogle Scholar
53.
Clarke  GNRohde  PLewinsohn  PMHops  HSeeley  JR Cognitive-behavioral treatment of adolescent depression: efficacy of acute group treatment and booster sessions.  J Am Acad Child Adolesc Psychiatry 1999;38 (3) 272- 279PubMedGoogle Scholar
54.
Antonuccio  DBurns  D Adolescents with depression [letter].  JAMA 2004;292 (21) 2577PubMedGoogle Scholar
55.
Mufson  LDorta  KPWickramaratne  PNomura  YOlfson  MWeissman  MM A randomized effectiveness trial of interpersonal psychotherapy for depressed adolescents.  Arch Gen Psychiatry 2004;61 (6) 577- 584PubMedGoogle Scholar
56.
National Institute for Health and Clinical Excellence, Depression in Children and Young People.  London, England National Institute for Health and Clinical Excellence2004;
57.
Burns  BJ Children and evidence-based practice.  Psychiatr Clin North Am 2003;26 (4) 955- 970PubMedGoogle Scholar
Original Article
October 2007

The Treatment for Adolescents With Depression Study (TADS): Long-term Effectiveness and Safety Outcomes

Arch Gen Psychiatry. 2007;64(10):1132-1143. doi:10.1001/archpsyc.64.10.1132
Abstract

Context  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.

Design and Setting  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.

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

Interventions  All treatments were administered per protocol.

Main Outcome Measures  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 × 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.

Trial Registration  clinicaltrials.gov Identifier: NCT00006286

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