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

Trials

Helen S Mayberg⁶  W Edward Craighead²  Drew Westen⁶  Vivianne Aponte Rivera⁶  James C Ritchie⁵  Thaddeus W W Pace⁶  Michael J Owens⁶  D Jeffrey Newport⁶  Charles B Nemeroff⁷  Michael Kutner¹  Becky Kinkead⁶  Mary E Kelley¹  Mark M Goodman⁴  Joseph F Cubells⁶  Elisabeth B Binder³  Boadie W Dunlop⁶ 

[1] Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA;Department of Psychology, Emory University, Atlanta, GA, USA;Max Planck Institute of Psychiatry, Munich, Germany;Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA;Department of Clinical Pathology, Emory University School of Medicine, Atlanta, GA, USA;Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1256 Briarcliff Road, Building A, 3rd Floor, Atlanta, GA 30306, USA;Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA

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

Others  :  1095477
DOI  :  10.1186/1745-6215-13-106

 received in 2011-11-15, accepted in 2012-05-22,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Dunlop et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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