Clinical trial NCT00909155: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2009-05-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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?

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

1. Forty participants who have a current Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revised (DSM-IV-TR) 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 In the event of suicidal ideation, subjects will be withdrawn from the study and referred for immediate treatment.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 magnetic resonance imaging (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 functional magnetic resonance imaging (fMRI)s 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.

Eligibility criteria: 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 central nervous system (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.

Primary outcomes:
measure: Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales
timeFrame: Study entry, 2 months, and at end of study (6 mos)
measure: Functional Magnetic Resonance Imaging (fMRI) Response to an Emotional Regulation Task.
timeFrame: At study entry, 2 months and end of study (6 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Madison Psychiatry Department
state: Wisconsin
Study officials:
affiliation: University of Wisconsin Madison Psychiatry Department
name: Gregory Kolden, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Wisconsin Madison Psychiatry Department
name: Michael Peterson, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heller AS, Johnstone T, Peterson MJ, Kolden GG, Kalin NH, Davidson RJ. Increased prefrontal cortex activity during negative emotion regulation as a predictor of depression symptom severity trajectory over 6 months. JAMA Psychiatry. 2013 Nov;70(11):1181-9. doi: 10.1001/jamapsychiatry.2013.2430.
citation: Heller AS, Johnstone T, Light SN, Peterson MJ, Kolden GG, Kalin NH, Davidson RJ. Relationships between changes in sustained fronto-striatal connectivity and positive affect in major depression resulting from antidepressant treatment. Am J Psychiatry. 2013 Feb;170(2):197-206. doi: 10.1176/appi.ajp.2012.12010014.
citation: Light SN, Heller AS, Johnstone T, Kolden GG, Peterson MJ, Kalin NH, Davidson RJ. Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder. Biol Psychiatry. 2011 Nov 15;70(10):962-8. doi: 10.1016/j.biopsych.2011.06.031. Epub 2011 Aug 25.
citation: Heller AS, Johnstone T, Shackman AJ, Light SN, Peterson MJ, Kolden GG, Kalin NH, Davidson RJ. Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22445-50. doi: 10.1073/pnas.0910651106. Epub 2009 Dec 22.