Imaging Predictors of Treatment Response in Depression

NCT00367341 | Completed Results DMC

• 1 other identifier: IRB00026176
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

While there are many effective options for treating a major depressive episode, there are no clinical markers that predict the likelihood of remission with an initial trial of either an antidepressant medication or psychotherapy. More critically, there are also no reliable predictors that might anticipate failure to such standard treatments either alone or in combination. This project will characterize imaging-based brain subtypes that distinguish groups of depressed patients who later remit or not to SSRI pharmacotherapy or cognitive behavior therapy (CBT), respectively. To define these subtypes, a prospectively-treated cohort of 100 patients will be randomized to receive either escitalopram (s-CIT) or CBT for the first 12 weeks, with non-remitters to either first treatment crossed over to receive an additional 12 weeks of treatment with combined treatment. Non-remitters to both treatments will thus define a relatively treatment resistant third subgroup. Resting-state 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) scans will be acquired prior to initiating antidepressant therapy, with pre-treatment scan patterns associated with three possible outcomes (CBT remission, s-CIT remission, and non-remission to both) assessed using multivariate analytic methods. A second PET scan, acquired early in the treatment course, will be used to assess the likelihood of response to the specific treatment first assigned. The proposed studies are a first step towards defining brain-based biomarkers predictive of differential treatment outcome in major depression; most critically, patterns distinguishing patients at risk for treatment resistance. Identification of such biomarkers has additional implications for future testing of novel therapies in patients with distinct brain signatures, including development of evidence-based treatment algorithms for individual patients.

Conditions

Major Depressive Disorder

Keywords

Depression, Treatment, Imaging

Outcome Measures

Primary Outcomes (1)

• Remission Defined as Hamilton Depression Rating Scale-17 Score of Less Than or Equal to 7 at 12 Weeks

  \# of study participants with Hamilton Depression-17-item score less than or equal to 7.

  Measured at week 12

Secondary Outcomes (1)

• Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks

  Measured at week 12.

Study Arms (2)

Escitalopram

OTHER

Drug: escitalopram

Cognitive Behavioral Therapy

OTHER

Behavioral: Cognitive Behavioral Therapy (CBT)

Interventions

escitalopram DRUG

Participants will receive treatment with escitalopram for 12 weeks.

Also known as: Lexapro

Escitalopram

Cognitive Behavioral Therapy (CBT) BEHAVIORAL

CBT will include 16 1 hour sessions provided over 12 weeks.

Also known as: Talk Therapy

Cognitive Behavioral Therapy

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female patients between the ages of 18 and 60. (no subjects with first episode over age 50. This is an attempt to exclude patients with 'vascular depression' who have a potentially different pathophysiology and treatment response compared to idiopathic MDD.
• DSM-IV criteria for unipolar Major Depressive Disorder.
• HAM-D (24 item) score \>/= 18 at Screening, \>/= 15 at Baseline.

You may not qualify if:

• Acceptable method of birth control (oral contraceptives, Depo-Provera, Norplant, condoms with spermicide. A vasectomy is acceptable in the framework of a stable monogamous relationship. Sexually inactive women must agree to contraception if they become sexually active during the study.
• Educational level, degree of understanding and reliability so that participation is feasible.
• Informed consent to participate and comply in the study.
• Known neurological disorders or documented head injury.
• Serious and unstable medical illnesses including diabetes, cardiovascular disease and cancer.
• Medical conditions with known mood changes (endocrine, autoimmune disorders)
• Co-morbid DSM-IV Axis I Diagnoses
• Lifetime history of Bipolar Disorder, Schizophrenia, and other Psychotic Disorders, or Obsessive Compulsive Disorder
• Alcohol abuse or dependence within the past six months, psychoactive substance abuse or dependence within the past six months.
• Clinical evidence of a severe Personality Disorder that would impede participation or completion of a controlled trial.
• ECT within the past 6 months.
• Previous failure to achieve a much improved status on CGI-Improvement (the equivalent of \>50% symptom reduction) with a course of CBT (defined as a minimum of 8 sessions during 8 weeks of a specified manual-driven therapy by a CBT trained therapist) or escitalopram (defined as a minimum of 6 weeks with the dose of 10 mgs achieved for at least 2 weeks)
• Use of concomitant medications with the exception of:
• Maintenance/prophylactic meds for stable medical conditions
• Ambien 5-10 mgs may be prescribed for occasional use (up to a single dose a week for insomnia, as long as it is not the night before a clinic visit, PET/fMRI study or ratings.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Related Publications (2)

• McGrath CL, Kelley ME, Holtzheimer PE, Dunlop BW, Craighead WE, Franco AR, Craddock RC, Mayberg HS. Toward a neuroimaging treatment selection biomarker for major depressive disorder. JAMA Psychiatry. 2013 Aug;70(8):821-9. doi: 10.1001/jamapsychiatry.2013.143.

  PMID: 23760393 RESULT

• McGrath CL, Kelley ME, Dunlop BW, Holtzheimer PE 3rd, Craighead WE, Mayberg HS. Pretreatment brain states identify likely nonresponse to standard treatments for depression. Biol Psychiatry. 2014 Oct 1;76(7):527-35. doi: 10.1016/j.biopsych.2013.12.005. Epub 2013 Dec 19.

  PMID: 24462230 DERIVED

Related Links

• website with study information

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Escitalopram; Cognitive Behavioral Therapy; Psychotherapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Behavior Therapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Helen Mayberg, MD
• Organization: Emory University School of Medicine

hmayber@emory.edu

404-727-6740

Study Officials

• Helen Mayberg, M.D.

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 18, 2006
• First Posted: August 22, 2006
• Study Start: August 1, 2006
• Primary Completion: August 1, 2011
• Study Completion: July 1, 2013
• Last Updated: January 9, 2014
• Results First Posted: January 9, 2014

Record last verified: 2013-11

Locations

US (1)