Clinical trial NCT00360399: Identifying Factors That Predict Antidepressant Treatment Response
Official title: Predictors of Antidepressant Treatment Response: The Emory CIDAR
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Keywords: Escitalopram
Duloxetine
Cognitive Behavioral Therapy
PET
fMRI
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2006-08-04
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will compare different treatments for depression in order to identify which factors predict effectiveness, and will include a companion study which investigates combining treatments and long term effectiveness.

Detailed description: Major depressive disorder (MDD) is a serious illness that affects a person's body, mood, and thoughts. The symptoms of MDD can interfere with a person's ability to work, study, sleep, eat, and enjoy activities that were once pleasurable. Antidepressant medications and psychotherapy are among the effective treatments for MDD. Individuals often respond to one type of treatment, but not another. Currently, however, doctors have no way of pre-determining which individuals will most benefit from which treatments. In the absence of practical predictors of MDD treatment response, the potential efficacy of existing MDD treatments is limited. This study will identify factors that may predict MDD treatment response by comparing the effectiveness of a selective serotonin reuptake inhibitor (SSRI), a serotonin norepinephrine reuptake inhibitor (SNRI), and cognitive behavioral therapy in people with MDD.

Participants in this 14-week, double-blind study will be randomly assigned to receive duloxetine (SNRI), escitalopram (SSRI), or cognitive behavioral therapy. During the first 2 weeks of screening, participants will complete questionnaires, clinician evaluations, an electrocardiogram, a personality assessment, a dexamethasone-corticotropin releasing factor test, a functional magnetic resonance imaging scan and provide blood samples. Upon completion of screening, patients will start the treatment to which they were randomized. Duloxetine and escitalopram are two medications that are approved by the Food and Drug Administration for the treatment of depression. Cognitive behavioral therapy is a talking therapy that is also used to treat depression. All participants assigned to take duloxetine or escitalopram will be seen by a study physician weekly for 6 weeks, and then every other week for the remainder of the study. Participants assigned to cognitive behavioral therapy will attend therapy sessions twice a week for the first 4 weeks, and then once a week for the remainder of the study. The following assessments will be performed for all participants at each visit: vital sign and weight measurements; clinician assessments; and self-report questionnaires. Additionally, blood samples will be taken at three visits through the trial and functional magnetic resonance imaging (fMRI) scans will be performed at selected times.

A companion study to the main CIDAR study offers participants further treatment. Participants who achieve remission after the initial 12 weeks of treatment will have the option to enroll in a 21-month follow-up study of maintenance treatment, with visits every three months to monitor for sustained response and relapse. Participants who do not remit will have the option to enroll in another 12-week treatment course, receiving a combination of CBT and medication. Participants who achieve response after this combination treatment will be eligible to receive maintenance combination treatment for up to an additional 18 months, monitored for sustained response and relapse. Participants who do not wish to enroll or continue in the companion study will be provided with a referral for treatment with another mental health provider.

Eligibility criteria: Inclusion Criteria:

* Current DSM-IV diagnosis of major depressive episode, as determined by Structured Clinical Interview for DSM-IV (SCID-IV)
* Primary diagnosis of MDD, based on prominence of symptoms and target for intervention (comorbid anxiety disorders, except obsessive-compulsive disorder (OCD), will not be criteria for exclusion)
* Score of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D17)
* Agrees to use an effective form of contraception and/or double barrier method

Exclusion Criteria:

* Previously treated for major depression with either medication or psychotherapy
* Current psychosis, dementia, eating disorder, or dissociative disorder
* History of bipolar disorder (I and II) or schizophrenia
* Alcohol or drug dependence within 3 months prior to study entry or current alcohol or drug abuse (excluding nicotine and caffeine), as assessed by medical history and urine drug screening
* Requires neuroleptic or mood stabilizer therapy in addition to depression treatment
* Presence of any acute or chronic medical disorder that could affect successful completion of the trial
* Medical contraindications that would preclude treatment with escitalopram or duloxetine
* Presence of practical issues that would likely prevent completion of the study (e.g., planned geographical relocation)
* Pregnant or breastfeeding
* Medical conditions that could prevent the safe use of MRI (e.g., pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, or other implants; steel worker)
* Medical conditions that could prevent the safe completion of a dexamethasone-corticotropin releasing factor (Dex-CRF) test (e.g., uncontrolled hypertension, significant abnormalities in EKG, anemia, known allergies against drugs)

Primary outcomes:
measure: Remission From Major Depressive Episode in Intent to Treat Sample
timeFrame: Up to 12 Weeks
measure: Remission From Major Depressive Episode Among Participants Who Completed the Intervention
timeFrame: Measured at Weeks 10 and 12
Secondary outcomes:
measure: Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, in Intent to Treat Sample
timeFrame: Up to 12 Weeks
measure: Number of Participants in Each Category of Response to Treatment of Depressive Symptoms, Among Participants Who Completed the Intervention
timeFrame: Measured at Weeks 10 and 12
measure: Number of Participants Experiencing Depression Recurrence Following Remission to Monotherapy Treatment
timeFrame: Measured at 6, 9, 12, 15, 18, 21, and 24 months
measure: Number of Participants Achieving Remission From Major Depressive Episode After 12 Weeks of Combined Treatment, for Those Patients Who do Not Achieve Remission With Monotherapy
timeFrame: Measured after 12 weeks of combined treatment
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Mood and Anxiety Disorders Program
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
Study officials:
affiliation: Emory University
name: Helen S. Mayberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: W. Edward Craighead, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. Predictors of remission in depression to individual and combined treatments (PReDICT): study protocol for a randomized controlled trial. Trials. 2012 Jul 9;13:106. doi: 10.1186/1745-6215-13-106.
citation: Brydges CR, Fiehn O, Mayberg HS, Schreiber H, Dehkordi SM, Bhattacharyya S, Cha J, Choi KS, Craighead WE, Krishnan RR, Rush AJ, Dunlop BW, Kaddurah-Daouk R; Mood Disorders Precision Medicine Consortium. Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature. Sci Rep. 2021 Oct 25;11(1):21011. doi: 10.1038/s41598-021-99845-1.
citation: Storebo OJ, Stoffers-Winterling JM, Vollm BA, Kongerslev MT, Mattivi JT, Jorgensen MS, Faltinsen E, Todorovac A, Sales CP, Callesen HE, Lieb K, Simonsen E. Psychological therapies for people with borderline personality disorder. Cochrane Database Syst Rev. 2020 May 4;5(5):CD012955. doi: 10.1002/14651858.CD012955.pub2.
citation: Kennedy JC, Dunlop BW, Craighead LW, Nemeroff CB, Mayberg HS, Craighead WE. Follow-up of monotherapy remitters in the PReDICT study: Maintenance treatment outcomes and clinical predictors of recurrence. J Consult Clin Psychol. 2018 Feb;86(2):189-199. doi: 10.1037/ccp0000279.
citation: Dunlop BW, Rajendra JK, Craighead WE, Kelley ME, McGrath CL, Choi KS, Kinkead B, Nemeroff CB, Mayberg HS. Functional Connectivity of the Subcallosal Cingulate Cortex And Differential Outcomes to Treatment With Cognitive-Behavioral Therapy or Antidepressant Medication for Major Depressive Disorder. Am J Psychiatry. 2017 Jun 1;174(6):533-545. doi: 10.1176/appi.ajp.2016.16050518. Epub 2017 Mar 24.