Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial.
BACKGROUND
Only about 60% of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor (SSRI). There are no data to guide clinicians on subsequent treatment strategy.


OBJECTIVE
To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI.


METHODS
Randomized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI, conducted at 6 US academic and community clinics from 2000-2006.


METHODS
Twelve weeks of: (1) switch to a second, different SSRI (paroxetine, citalopram, or fluoxetine, 20-40 mg); (2) switch to a different SSRI plus cognitive behavioral therapy; (3) switch to venlafaxine (150-225 mg); or (4) switch to venlafaxine plus cognitive behavioral therapy.


METHODS
Clinical Global Impressions-Improvement score of 2 or less (much or very much improved) and a decrease of at least 50% in the Children's Depression Rating Scale-Revised (CDRS-R); and change in CDRS-R over time.


RESULTS
Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate (54.8%; 95% confidence interval [CI], 47%-62%) than a medication switch alone (40.5%; 95% CI, 33%-48%; P = .009), but there was no difference in response rate between venlafaxine and a second SSRI (48.2%; 95% CI, 41%-56% vs 47.0%; 95% CI, 40%-55%; P = .83). There were no differential treatment effects on change in the CDRS-R, self-rated depressive symptoms, suicidal ideation, or on the rate of harm-related or any other adverse events. There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment.


CONCLUSIONS
For adolescents with depression not responding to an adequate initial treatment with an SSRI, the combination of cognitive behavioral therapy and a switch to another antidepressant resulted in a higher rate of clinical response than did a medication switch alone. However, a switch to another SSRI was just as efficacious as a switch to venlafaxine and resulted in fewer adverse effects.


BACKGROUND
clinicaltrials.gov Identifier: NCT00018902.
Brent
David
D
Emslie
Graham
G
Clarke
Greg
G
Wagner
Karen Dineen
KD
Asarnow
Joan Rosenbaum
JR
Keller
Marty
M
Vitiello
Benedetto
B
Ritz
Louise
L
Iyengar
Satish
S
Abebe
Kaleab
K
Birmaher
Boris
B
Ryan
Neal
N
Kennard
Betsy
B
Hughes
Carroll
C
DeBar
Lynn
L
McCracken
James
J
Strober
Michael
M
Suddath
Robert
R
Spirito
Anthony
A
Leonard
Henrietta
H
Melhem
Nadine
N
Porta
Giovanna
G
Onorato
Matthew
M
Zelazny
Jamie
J
D000293:Adolescent; D015283:Citalopram / Q000627:therapeutic use; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003511:Cyclohexanols / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000628:therapy*; D004351:Drug Resistance; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D008297:Male; D017374:Paroxetine / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D015283:Citalopram; D003511:Cyclohexanols; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride