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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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Schedule of events for PReDICT study. NOTE: Remitters to the acute (monotherapy) treatment phase enter into the extension follow-up phase beginning at week 12. BDI, Beck Depression Inventory; CGI, Clinical Global Impression; CTQ, Childhood Trauma Questionnaire: Dex/CRH, Dexamethasone Corticotropin Releasing Hormone test; DHUS, Daily Hassles and Uplifts Scale; DNA, Deoxyribonucleic acid; EHEI, Early Home Environment Interview; HARS, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; IPDE, International Personality Disorders Examination; LES, Life Experiences Survey; LIFE, Longitudinal Interview Follow-up Evaluation; MADRS, Montgomery Depression Rating Scale; MRI, Magnetic resonance imaging; mRNA, Messenger ribonucleic acid; PABS, Patient Attitudes and Beliefs Scale; PE, Physical Exam; QIDS, Quick Inventory of Depressive Symptoms; Q-LES-Q, Quality of Life Enjoyment and Satisfaction Questionnaire; SCID, Structured Clinical Interview for DSM-IV; SDS, Sheehan Disability Scale; SWAP, Shedler-Westen Assessment Procedure, 2nd Ed.
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Figure 2: Schedule of events for PReDICT study. NOTE: Remitters to the acute (monotherapy) treatment phase enter into the extension follow-up phase beginning at week 12. BDI, Beck Depression Inventory; CGI, Clinical Global Impression; CTQ, Childhood Trauma Questionnaire: Dex/CRH, Dexamethasone Corticotropin Releasing Hormone test; DHUS, Daily Hassles and Uplifts Scale; DNA, Deoxyribonucleic acid; EHEI, Early Home Environment Interview; HARS, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; IPDE, International Personality Disorders Examination; LES, Life Experiences Survey; LIFE, Longitudinal Interview Follow-up Evaluation; MADRS, Montgomery Depression Rating Scale; MRI, Magnetic resonance imaging; mRNA, Messenger ribonucleic acid; PABS, Patient Attitudes and Beliefs Scale; PE, Physical Exam; QIDS, Quick Inventory of Depressive Symptoms; Q-LES-Q, Quality of Life Enjoyment and Satisfaction Questionnaire; SCID, Structured Clinical Interview for DSM-IV; SDS, Sheehan Disability Scale; SWAP, Shedler-Westen Assessment Procedure, 2nd Ed.

Mentions: The schedule of assessments is presented in Figure2. After signing the informed consent form, study participants meet with a staff member for an initial psychiatric interview. The results of this initial interview are then presented to a study psychiatrist, who subsequently conducts a 30 to 60-min diagnostic evaluation, including medical history and previous treatment history. Patients who remain eligible then complete the Structured Clinical Interview for DSM-IV (SCID)[47,48] administered by a trained clinical interviewer. Symptom severity is assessed by the SCID interviewer who also administers the HDRS-24 plus atypical items[49,50] using a structured interview guide[51], Montgomery-Asberg Depression Rating Scale (MADRS)[52,53], Hamilton Anxiety Rating Scale (HARS)[54], and Clinical Global Impression scale for Severity (CGI-S)[55]. Patients are then evaluated to ensure adequate physical health and to identify potential medical causes for a major depressive episode. This evaluation includes: a medical review of systems, physical exam, electrocardiogram and laboratory assessments (comprehensive metabolic panel, complete blood count, thyroid-stimulating hormone level, pregnancy test, and urinalysis and urine drug screen). Demographic variables and family history of psychiatric illness are collected via self-report. Childhood trauma history is assessed via the Childhood Trauma Questionnaire (CTQ)[56] and the Early Home Environment Interview (EHEI)[57]. Inclusion and exclusion criteria are listed below. Patients who meet all eligibility criteria undergo phlebotomy for measurement of inflammatory markers and extraction of mRNA and DNA. Subsequently, patients complete the fMRI and a half-day CIN outpatient hospital stay during which the Dex/CRH test is performed. The targeted time to complete all pre-treatment assessments from screening to randomization is 10 days.


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)

Schedule of events for PReDICT study. NOTE: Remitters to the acute (monotherapy) treatment phase enter into the extension follow-up phase beginning at week 12. BDI, Beck Depression Inventory; CGI, Clinical Global Impression; CTQ, Childhood Trauma Questionnaire: Dex/CRH, Dexamethasone Corticotropin Releasing Hormone test; DHUS, Daily Hassles and Uplifts Scale; DNA, Deoxyribonucleic acid; EHEI, Early Home Environment Interview; HARS, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; IPDE, International Personality Disorders Examination; LES, Life Experiences Survey; LIFE, Longitudinal Interview Follow-up Evaluation; MADRS, Montgomery Depression Rating Scale; MRI, Magnetic resonance imaging; mRNA, Messenger ribonucleic acid; PABS, Patient Attitudes and Beliefs Scale; PE, Physical Exam; QIDS, Quick Inventory of Depressive Symptoms; Q-LES-Q, Quality of Life Enjoyment and Satisfaction Questionnaire; SCID, Structured Clinical Interview for DSM-IV; SDS, Sheehan Disability Scale; SWAP, Shedler-Westen Assessment Procedure, 2nd Ed.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Schedule of events for PReDICT study. NOTE: Remitters to the acute (monotherapy) treatment phase enter into the extension follow-up phase beginning at week 12. BDI, Beck Depression Inventory; CGI, Clinical Global Impression; CTQ, Childhood Trauma Questionnaire: Dex/CRH, Dexamethasone Corticotropin Releasing Hormone test; DHUS, Daily Hassles and Uplifts Scale; DNA, Deoxyribonucleic acid; EHEI, Early Home Environment Interview; HARS, Hamilton Anxiety Rating Scale; HDRS, Hamilton Depression Rating Scale; IPDE, International Personality Disorders Examination; LES, Life Experiences Survey; LIFE, Longitudinal Interview Follow-up Evaluation; MADRS, Montgomery Depression Rating Scale; MRI, Magnetic resonance imaging; mRNA, Messenger ribonucleic acid; PABS, Patient Attitudes and Beliefs Scale; PE, Physical Exam; QIDS, Quick Inventory of Depressive Symptoms; Q-LES-Q, Quality of Life Enjoyment and Satisfaction Questionnaire; SCID, Structured Clinical Interview for DSM-IV; SDS, Sheehan Disability Scale; SWAP, Shedler-Westen Assessment Procedure, 2nd Ed.
Mentions: The schedule of assessments is presented in Figure2. After signing the informed consent form, study participants meet with a staff member for an initial psychiatric interview. The results of this initial interview are then presented to a study psychiatrist, who subsequently conducts a 30 to 60-min diagnostic evaluation, including medical history and previous treatment history. Patients who remain eligible then complete the Structured Clinical Interview for DSM-IV (SCID)[47,48] administered by a trained clinical interviewer. Symptom severity is assessed by the SCID interviewer who also administers the HDRS-24 plus atypical items[49,50] using a structured interview guide[51], Montgomery-Asberg Depression Rating Scale (MADRS)[52,53], Hamilton Anxiety Rating Scale (HARS)[54], and Clinical Global Impression scale for Severity (CGI-S)[55]. Patients are then evaluated to ensure adequate physical health and to identify potential medical causes for a major depressive episode. This evaluation includes: a medical review of systems, physical exam, electrocardiogram and laboratory assessments (comprehensive metabolic panel, complete blood count, thyroid-stimulating hormone level, pregnancy test, and urinalysis and urine drug screen). Demographic variables and family history of psychiatric illness are collected via self-report. Childhood trauma history is assessed via the Childhood Trauma Questionnaire (CTQ)[56] and the Early Home Environment Interview (EHEI)[57]. Inclusion and exclusion criteria are listed below. Patients who meet all eligibility criteria undergo phlebotomy for measurement of inflammatory markers and extraction of mRNA and DNA. Subsequently, patients complete the fMRI and a half-day CIN outpatient hospital stay during which the Dex/CRH test is performed. The targeted time to complete all pre-treatment assessments from screening to randomization is 10 days.

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