Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: predictors and moderators of treatment response.
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.
Asarnow
Joan Rosenbaum
JR
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.
Emslie
Graham
G
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.
Clarke
Greg
G
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.
Wagner
Karen Dineen
KD
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.
Spirito
Anthony
A
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.
Vitiello
Benedetto
B
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.
Iyengar
Satish
S
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.
Shamseddeen
Wael
W
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.
Ritz
Louise
L
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.
Birmaher
Boris
B
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.
Ryan
Neal
N
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.
Kennard
Betsy
B
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.
Mayes
Taryn
T
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.
DeBar
Lynn
L
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.
McCracken
James
J
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.
Strober
Michael
M
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.
Suddath
Robert
R
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.
Leonard
Henrietta
H
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.
Porta
Giovanna
G
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.
Keller
Martin
M
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.
Brent
David
D
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.
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
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride