title: Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: predictors and moderators of treatment response.
abstract: OBJECTIVE
  To advance knowledge regarding strategies for treating selective serotonin reuptake inhibitor (SSRI)-resistant depression in adolescents, we conducted a randomized controlled trial evaluating alternative treatment strategies. In primary analyses, cognitive-behavioral therapy (CBT) combined with medication change was associated with higher rates of positive response to short-term (12-week) treatment than medication alone. This study examines predictors and moderators of treatment response, with the goal of informing efforts to match youths to optimal treatment strategies.
  
  
  METHODS
  Youths who had not improved during an adequate SSRI trial (N = 334) were randomized to an alternative SSRI, an alternative SSRI plus CBT, venlafaxine, or venlafaxine plus CBT. Analyses examined predictors and moderators of treatment response.
  
  
  RESULTS
  Less severe depression, less family conflict, and absence of nonsuicidal self-injurious behavior predicted better treatment response status. Significant moderators of response to CBT + medication (combined) treatment were number of comorbid disorders and abuse history; hopelessness was marginally significant. The CBT/combined treatment superiority over medication alone was more evident among youths who had more comorbid disorders (particularly attention-deficit/hyperactivity disorder and anxiety disorders), no abuse history, and lower hopelessness. Further analyses revealed a stronger effect of combined CBT + medication treatment among youths who were older and white and had no nonsuicidal self-injurious behavior and longer prestudy pharmacotherapy.
  
  
  CONCLUSIONS
  Combined treatment with CBT and antidepressant medication may be more advantageous for adolescents whose depression is comorbid with other disorders. Given the additional costs of adding CBT to medication, consideration of moderators in clinical decision making can contribute to a more personalized and effective approach to treatment.
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University. Electronic address: jasarnow@mednet.ucla.edu.
authors.forename: Joan Rosenbaum
authors.initials: JR
authors.lastname: Asarnow
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Graham
authors.initials: G
authors.lastname: Emslie
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Greg
authors.initials: G
authors.lastname: Clarke
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Anthony
authors.initials: A
authors.lastname: Spirito
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Satish
authors.initials: S
authors.lastname: Iyengar
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Wael
authors.initials: W
authors.lastname: Shamseddeen
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Louise
authors.initials: L
authors.lastname: Ritz
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Neal
authors.initials: N
authors.lastname: Ryan
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Betsy
authors.initials: B
authors.lastname: Kennard
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Taryn
authors.initials: T
authors.lastname: Mayes
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Lynn
authors.initials: L
authors.lastname: DeBar
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: James
authors.initials: J
authors.lastname: McCracken
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Michael
authors.initials: M
authors.lastname: Strober
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Robert
authors.initials: R
authors.lastname: Suddath
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Leonard
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Porta
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: Martin
authors.initials: M
authors.lastname: Keller
authors.affiliation: Drs. Asarnow, McCracken, Strober, and Suddath are with the Department of Psychiatry, University of California-Los Angeles; Drs. Brent, Iyengar, Shamseddeen, Ryan, and Birmaher and Ms. Porta are with the University of Pittsburgh; Drs. Emslie and Kennard and Ms. Mayes are with the University of Texas Southwestern Medical Center at Dallas; Drs. Clarke and DeBar are with the Kaiser Permanente Center for Health Sciences; Dr. Wagner is with the University of Texas Medical Branch; Drs. Spirito and Keller are with the Department of Psychiatry, Brown University; Dr. Vitiello and Ms. Ritz are with the National Institute of Mental Health; and Dr. Leonard, now deceased, was formerly with Brown University.
authors.forename: David
authors.initials: D
authors.lastname: Brent
mesh_terms: D000293:Adolescent; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004351:Drug Resistance; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use; D010555:Personality Inventory; D011379:Prognosis; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride
chemical_list: D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride