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
  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.
  
  
  CONCLUSIONS
  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.
authors: 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
authors: Boadie W
authors: BW
authors: Dunlop
authors: Elisabeth B
authors: EB
authors: Binder
authors: Joseph F
authors: JF
authors: Cubells
authors: Mark M
authors: MM
authors: Goodman
authors: Mary E
authors: ME
authors: Kelley
authors: Becky
authors: B
authors: Kinkead
authors: Michael
authors: M
authors: Kutner
authors: Charles B
authors: CB
authors: Nemeroff
authors: D Jeffrey
authors: DJ
authors: Newport
authors: Michael J
authors: MJ
authors: Owens
authors: Thaddeus W W
authors: TW
authors: Pace
authors: James C
authors: JC
authors: Ritchie
authors: Vivianne Aponte
authors: VA
authors: Rivera
authors: Drew
authors: D
authors: Westen
authors: W Edward
authors: WE
authors: Craighead
authors: Helen S
authors: HS
authors: Mayberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004359:Drug Therapy, Combination; D000068736:Duloxetine Hydrochloride; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010551:Personality; D011237:Predictive Value of Tests; D012074:Remission Induction; D012107:Research Design; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D015415:Biomarkers; D013876:Thiophenes; D015283:Citalopram; D000068736:Duloxetine Hydrochloride