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

Dunlop BW, Binder EB, Cubells JF, Goodman MM, Kelley ME, Kinkead B, Kutner M, Nemeroff CB, Newport DJ, Owens MJ, Pace TW, Ritchie JC, Rivera VA, Westen D, Craighead WE, Mayberg HS - Trials (2012)

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1256 Briarcliff Road, Building A, 3rd Floor, Atlanta, GA 30306, USA. bdunlop@emory.edu

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.

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PReDICT study design.
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Figure 1: PReDICT study design.

Mentions: Four hundreda treatment-naïve patients with a primary diagnosis of MDD and HDRS-17 scores ≥18 at screening and ≥15 at the baseline visit are to be randomly assigned equally to one of three possible treatments: (1) a selective serotonin reuptake inhibitor (SSRI, escitalopram); (2) a serotonin norepinephrine reuptake inhibitor (SNRI, duloxetine); or (3) individual cognitive behavior therapy (CBT). Initial treatment consists of a 12-week course with one of these monotherapies. Patients who meet criteria for full remission of their MDD are followed for a 21-month follow-up phase to monitor for depression recurrence. Patients who do not remit after the 12-week monotherapy acute treatment phase are offered another 12 weeks of acute treatment, during which they receive combination therapy with study medication plus CBT. The overall study design is presented in Figure1.


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

Dunlop BW, Binder EB, Cubells JF, Goodman MM, Kelley ME, Kinkead B, Kutner M, Nemeroff CB, Newport DJ, Owens MJ, Pace TW, Ritchie JC, Rivera VA, Westen D, Craighead WE, Mayberg HS - Trials (2012)

PReDICT study design.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539869&req=5

Figure 1: PReDICT study design.
Mentions: Four hundreda treatment-naïve patients with a primary diagnosis of MDD and HDRS-17 scores ≥18 at screening and ≥15 at the baseline visit are to be randomly assigned equally to one of three possible treatments: (1) a selective serotonin reuptake inhibitor (SSRI, escitalopram); (2) a serotonin norepinephrine reuptake inhibitor (SNRI, duloxetine); or (3) individual cognitive behavior therapy (CBT). Initial treatment consists of a 12-week course with one of these monotherapies. Patients who meet criteria for full remission of their MDD are followed for a 21-month follow-up phase to monitor for depression recurrence. Patients who do not remit after the 12-week monotherapy acute treatment phase are offered another 12 weeks of acute treatment, during which they receive combination therapy with study medication plus CBT. The overall study design is presented in Figure1.

Bottom Line: 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.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1256 Briarcliff Road, Building A, 3rd Floor, Atlanta, GA 30306, USA. bdunlop@emory.edu

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.

Show MeSH
Related in: MedlinePlus