Brain Imaging Techniques That Predict Antidepressant Responsiveness

Official Title: “Non-Invasive Brain Imaging Techniques That Predict Antidepressant Responsiveness and Provide Insights Into the Mechanism of Action of Venlafaxine ER vs. Fluoxetine”

Do functional brain changes occur during Venlafaxine ER (extended release) versus Fluoxetine treatment and do changes in selective structures, such as the amygdala, predict treatment response?

This is a single site, controlled, double-blind study of outpatients. There are two arms:

1. Forty participants who have a current DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised) diagnosis of Major Depression will be recruited. These subjects will be randomized to receive one of two antidepressant medications: Fluoxetine or Venlafaxine ER for the duration of the study. Subjects will gradually be titrated onto the medications and will be seen in the clinic up to 18 times for medication checks, to monitor side effects and depressive symptoms, including suicidal ideation. In the event of suicidal ideation, subjects will be withdrawn from the study and referred for immediate treatment.

2. Twenty normal control subjects with no current or past DSM-IV-TR diagnosis and will receive no medication. Normal control subjects will have up to 5 visits while in the study.

Subjects will contact study staff to complete a phone screen and then eligible subjects will complete a clinic screen. Subjects will then be scheduled to attend the MRI simulation visit and if subjects continue to meet entrance criteria, they will be scheduled for the first MRI. Following the first MRI, subjects in the medication conditions will begin receiving medication.

All subjects will undergo 3 fMRIs during the study: at the beginning of the study, approximately 8 weeks and 26 weeks later. During the MRI, subjects will view slides with positive and negative emotional content. Subjects will complete various clinical interviews or rating scales assessing mood and side effects at each of the visits.

Intervention(s) in this Clinical Trial

• Drug: Venlafaxine ERT
  • Titrated to a minimum dose of 75mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 37.5 mg; Days 7-14: 75 mg; Days 15-180: 75-300mg based on clinician assessment. Titration rate is a maximum of 75mg/7d.
• Drug: Fluoxetine
  • Titrated to a minimum dose of 20mg. Further titration based on clinician assessment at followup visits. Intervention to continue through completion of study (180 days). Initial titration: Days 1-7: 20mg; Days 7-14: 20mg; Days 15-180: 20-80mg based on clinician assessment. Titration rate is a maximum of 20mg/7d

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Currently depressed subjects; Randomized medication treatment with Venlafaxine ERT
• Active Comparator: 2
  • Currently depressed subjects; Randomized medication treatment with Fluoxetine
• No Intervention: Control
  • Non-psychiatric subjects with no past or current history of depression. Subjects will receive no medication

Primary Measures

• Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating scales
  • Time Frame: Study entry, 2 months, and at end of study (6 mos)
    Safety Issue?: No
• fMRI response to an emotional regulation task.
  • Time Frame: At study entry, 2 months and end of study (6 months)
    Safety Issue?: No

Secondary Measures

• Vitals
  • Time Frame: each visit
    Safety Issue?: Yes

Inclusion Criteria:

• Intervention Group:
• Right-handed,
• Be able to lie still on their back for about 120 minutes,
• Meet DSM-IV criteria for major depression (single or recurrent),
• Have had depressive symptoms for at least 1 month prior to screen visit,
• Must score an 18 or above on the Hamilton-D at both the initial screening visit and first fMRI scanning session,
• Able to understand and speak English.
• Control Group: same as above with the exception of no diagnosis of psychiatric disorder.

Exclusion Criteria:

• Any history of seizures,
• Current medical disorders that might make interpretation of scan data difficult,
• Diabetes requiring insulin treatment,
• A serious heart disorder or subjects who have had a heart attack within the last 3 months,
• Subjects who meet DSM-IV criteria for alcohol/drug abuse or dependence within the last six months,
• Other current DSM-IV Axis I or Axis II diagnoses,
• A personal or family history of bipolar disorder,
• Current use of medication that affects CNS function,
• Participation in the last 30 days in a clinical study involving an investigational drug,
• A subject with metallic implants, such as prostheses, shrapnel or aneurysm clip-S, or persons with electronic implants, such as cardiac pacemakers. The magnetic field generated by the MRI machine can cause a displacement or malfunctioning of these devices.
• A subject who is claustrophobic,
• Female subjects who are pregnant,
• A subject at serious risk for suicide,
• Diagnosis of cancer in the past 3 years and/or has active neoplastic disease,
• Nonresponse to 2 adequate trials of antidepressant treatment,
• Nonresponse to 2 adequate trials of an empirically supported psychotherapy.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: University of Wisconsin, Madison Other

Overall Clinical Trial Officials and Contacts

Gregory Kolden, Ph.D. Principal Investigator University of Wisconsin Madison Psychiatry Department  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00909155

Study ID Number: 0600B-100953

ClinicalTrials.gov Identifier: NCT00909155

Health Authority: United States: Institutional Review Board