Predictors of remission in depression to individual and combined treatments (PReDICT): Study protocol for a randomized controlled trial

Boadie W. Dunlop, Elisabeth B. Binder, Joseph F. Cubells, Mark M. Goodman, Mary E. Kelley, Becky Kinkead, Michael Kutner, Charles B. Nemeroff, D. J. Newport, Michael J. Owens, Thaddeus Wesley Warren Pace, James C. Ritchie, Vivianne A. Rivera, Drew Westen, W. E. Craighead, Helen S. Mayberg

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background: Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient's treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition.Methods/design: Treatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30-60 mg/d); or (3) escitalopram (10-20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes.Discussion: The PReDICT study's evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness.Trial registration: Clinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007.

Original languageEnglish (US)
Article number106
JournalTrials
Volume13
DOIs
StatePublished - Jul 9 2012
Externally publishedYes

Fingerprint

Clinical Protocols
Randomized Controlled Trials
Depression
Therapeutics
Major Depressive Disorder
Corticotropin-Releasing Hormone
Random Allocation
Dexamethasone
Biomarkers
History
Magnetic Resonance Imaging
Personality Assessment
Gene Expression
Recurrence
Citalopram
Selection Bias
Cognitive Therapy
Statistical Models

Keywords

  • Antidepressive agents
  • Clinical research protocol
  • Cognitive behavior therapy
  • Depression
  • Genetic polymorphisms
  • HPA Axis
  • Inflammation
  • Magnetic resonance imaging
  • Personality disorders
  • Personalized medicine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Cite this

Dunlop, B. W., Binder, E. B., Cubells, J. F., Goodman, M. M., Kelley, M. E., Kinkead, B., ... Mayberg, H. S. (2012). Predictors of remission in depression to individual and combined treatments (PReDICT): Study protocol for a randomized controlled trial. Trials, 13, [106]. https://doi.org/10.1186/1745-6215-13-106

Predictors of remission in depression to individual and combined treatments (PReDICT) : Study protocol for a randomized controlled trial. / Dunlop, Boadie W.; Binder, Elisabeth B.; Cubells, Joseph F.; Goodman, Mark M.; Kelley, Mary E.; Kinkead, Becky; Kutner, Michael; Nemeroff, Charles B.; Newport, D. J.; Owens, Michael J.; Pace, Thaddeus Wesley Warren; Ritchie, James C.; Rivera, Vivianne A.; Westen, Drew; Craighead, W. E.; Mayberg, Helen S.

In: Trials, Vol. 13, 106, 09.07.2012.

Research output: Contribution to journalArticle

Dunlop, BW, Binder, EB, Cubells, JF, Goodman, MM, Kelley, ME, Kinkead, B, Kutner, M, Nemeroff, CB, Newport, DJ, Owens, MJ, Pace, TWW, Ritchie, JC, Rivera, VA, Westen, D, Craighead, WE & Mayberg, HS 2012, 'Predictors of remission in depression to individual and combined treatments (PReDICT): Study protocol for a randomized controlled trial', Trials, vol. 13, 106. https://doi.org/10.1186/1745-6215-13-106
Dunlop, Boadie W. ; Binder, Elisabeth B. ; Cubells, Joseph F. ; Goodman, Mark M. ; Kelley, Mary E. ; Kinkead, Becky ; Kutner, Michael ; Nemeroff, Charles B. ; Newport, D. J. ; Owens, Michael J. ; Pace, Thaddeus Wesley Warren ; Ritchie, James C. ; Rivera, Vivianne A. ; Westen, Drew ; Craighead, W. E. ; Mayberg, Helen S. / Predictors of remission in depression to individual and combined treatments (PReDICT) : Study protocol for a randomized controlled trial. In: Trials. 2012 ; Vol. 13.
@article{9becd157fb724aff81167cef7aa44f60,
title = "Predictors of remission in depression to individual and combined treatments (PReDICT): Study protocol for a randomized controlled trial",
abstract = "Background: Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient's treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition.Methods/design: Treatment-na{\"i}ve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30-60 mg/d); or (3) escitalopram (10-20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes.Discussion: The PReDICT study's evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness.Trial registration: Clinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007.",
keywords = "Antidepressive agents, Clinical research protocol, Cognitive behavior therapy, Depression, Genetic polymorphisms, HPA Axis, Inflammation, Magnetic resonance imaging, Personality disorders, Personalized medicine",
author = "Dunlop, {Boadie W.} and Binder, {Elisabeth B.} and Cubells, {Joseph F.} and Goodman, {Mark M.} and Kelley, {Mary E.} and Becky Kinkead and Michael Kutner and Nemeroff, {Charles B.} and Newport, {D. J.} and Owens, {Michael J.} and Pace, {Thaddeus Wesley Warren} and Ritchie, {James C.} and Rivera, {Vivianne A.} and Drew Westen and Craighead, {W. E.} and Mayberg, {Helen S.}",
year = "2012",
month = "7",
day = "9",
doi = "10.1186/1745-6215-13-106",
language = "English (US)",
volume = "13",
journal = "Trials",
issn = "1745-6215",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Predictors of remission in depression to individual and combined treatments (PReDICT)

T2 - Study protocol for a randomized controlled trial

AU - Dunlop, Boadie W.

AU - Binder, Elisabeth B.

AU - Cubells, Joseph F.

AU - Goodman, Mark M.

AU - Kelley, Mary E.

AU - Kinkead, Becky

AU - Kutner, Michael

AU - Nemeroff, Charles B.

AU - Newport, D. J.

AU - Owens, Michael J.

AU - Pace, Thaddeus Wesley Warren

AU - Ritchie, James C.

AU - Rivera, Vivianne A.

AU - Westen, Drew

AU - Craighead, W. E.

AU - Mayberg, Helen S.

PY - 2012/7/9

Y1 - 2012/7/9

N2 - Background: Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient's treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition.Methods/design: Treatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30-60 mg/d); or (3) escitalopram (10-20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes.Discussion: The PReDICT study's evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness.Trial registration: Clinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007.

AB - Background: Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient's treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition.Methods/design: Treatment-naïve adults aged 18 to 65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: (1) cognitive behavior therapy (CBT, 16 sessions); (2) duloxetine (30-60 mg/d); or (3) escitalopram (10-20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin-releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occurs at an early time-point in treatment, and upon completion of 12-week treatment, when a second Dex/CRH test is also conducted. Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes.Discussion: The PReDICT study's evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness.Trial registration: Clinicaltrials.gov Identifier: NCT00360399. Registered 02 AUG 2006. First patient randomized 09 FEB 2007.

KW - Antidepressive agents

KW - Clinical research protocol

KW - Cognitive behavior therapy

KW - Depression

KW - Genetic polymorphisms

KW - HPA Axis

KW - Inflammation

KW - Magnetic resonance imaging

KW - Personality disorders

KW - Personalized medicine

UR - http://www.scopus.com/inward/record.url?scp=84863509415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863509415&partnerID=8YFLogxK

U2 - 10.1186/1745-6215-13-106

DO - 10.1186/1745-6215-13-106

M3 - Article

C2 - 22776534

AN - SCOPUS:84863509415

VL - 13

JO - Trials

JF - Trials

SN - 1745-6215

M1 - 106

ER -