A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder - Full Text View

Sponsor:	University Health Network, Toronto
Collaborator:	Eli Lilly and Company
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00188942

Purpose

This study employs functional magnetic resonance imaging to compare brain activation patterns during a depressive episode in patients diagnosed with bipolar disorder, major depressive disorder, and a group of healthy control subjects. Depressed patients will be treated with a combination of fluoxetine and olanzapine and undergo MRI scans before, during, and after pharmacotherapy.

Condition	Intervention	Phase
Bipolar Disorder Major Depressive Disorder	Drug: Fluoxetine Drug: Olanzapine Procedure: Functional Magnetic Resonance Imaging	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Neural Correlates of Emotional Processing in Depressed and Remitted Bipolar and Unipolar Depressed Subjects: An fMRI Investigation

Resource links provided by NLM:

MedlinePlus related topics: Anxiety Bipolar Disorder Depression MRI Scans

Drug Information available for: Fluoxetine Fluoxetine hydrochloride Olanzapine

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:

MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy.
17 Item - Hamilton Depression Rating Scale - Weekly
Clinical Global Impression - Improvement/Severity - Weekly
Young Mania Rating Scale - Weekly

Secondary Outcome Measures:

Positive Affect Negative Affect Scale
Beck Depression Inventory
State Trait Anxiety Index
Behavioural Activation/Inhibition Scale
SexFX Scale
AMDP-5 Symptom Questionnaire

Estimated Enrollment:	45
Study Start Date:	February 2005
Estimated Study Completion Date:	December 2006

Detailed Description:

The purpose of this study is to further characterize the neural correlates of affective processing in BD and MDD subjects using fMRI. Subjects who meet criteria for a major depressive episode in the context of BD (n=15); MDD (n=15) and a group of psychiatrically unaffected control subjects (CS, n=15) will undergo four fMRI scans while experiencing a temporary mood induction through the presentation of affective imagery from the International Affective Picture System (IAPS). Both BD and MDD subjects will receive the same combination pharmacotherapy to treat the depression, with fMRI data acquired before, and 1, 3, 6 weeks following pharmacotherapy initiation. Positive, negative, and neutral affective visual stimuli will be presented in a blocked design.

Comparison(s): The effects of time and group will be analyzed in factorial models. Regions of interest that demonstrate significant group-by-time interactions will be further correlated with self-report and clinician-rated psychometric indices.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria: (All three groups)

age 18-55 years
satisfactory physical health
education level and a degree of understanding to communicate effectively with the investigator c
capable of providing informed consent
female subjects of childbearing potential, a medically accepted means of contraception.

Additional inclusion criteria for the patient groups include

DSM-IV-TR criteria for a diagnosis of BD or MDD
currently meeting criteria for an MDE and
a Hamilton Depression Rating Scale 17 Item (HDRS-17) score of > 17
blood indices within normal clinical ranges.

Exclusion Criteria: (All three groups)

DSM-IV-TR criteria for substance abuse or dependence (except nicotine or caffeine) within the past 6 months
comorbid neurological or other major psychiatric disorders as defined in the DSM-IV-TR;
history of neurological trauma resulting in loss of consciousness;
uncorrected hypothyroidism or hyperthyroidism, including elevated thyroid stimulating hormone (TSH);
other unstable medical condition;
female subjects who are pregnant or nursing;

Additional exclusion criteria for the BD and MDD group include:

prior failure to respond to fluoxetine and olanzapine in combination at adequate dose and duration;
evidence of serious risk of suicide based on clinician assessment and/or HRSD suicide item > 3;
course of ECT (electroconvulsive therapy) in the preceding 6 months;
Young Mania Rating Scale (YMRS) > 7;
administration of fluoxetine within previous 4 weeks;
treatment resistance as defined by the failure of two antidepressant trials from dissimilar classes
Hyperglycemia or diabetes mellitus as defined by a fasting blood glucose value of > 125 mg/dl.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00188942

Contacts

Contact: Sidney H Kennedy, MD, FRCPC	416 340 3888	sidney.kennedy@uhn.on.ca
Contact: Jakub Z. Konarski, MSc	416 603 5800 ext 3588	jakub.konarski@utoronto.ca

Locations

Canada, Ontario
University Health Network - Toronto Western Division	Recruiting
Toronto, Ontario, Canada, M5T2S8
Contact: Roger S. McIntyre, MD, FRCPC 416 603 5279 roger.mcintyre@uhn.on.ca
Principal Investigator: Roger S. McIyntyre, MD, FRCPC
University Health Network - Toronto General Division	Recruiting
Toronto, Ontario, Canada, M5G2C4
Contact: Sidney H. Kennedy, MD, FRCPC 416 340 3888 sidney.kennedy@uhn.on.ca
Principal Investigator: Sidney H. Kennedy, MD, FRCPC

Sponsors and Collaborators

University Health Network, Toronto

Eli Lilly and Company

Investigators

Principal Investigator:

Sidney H. Kennedy, MD, FRCPC

University Health Network, Department of Psychiatry, University of Toronto

More Information

Publications:

Kumari V, Mitterschiffthaler MT, Teasdale JD, Malhi GS, Brown RG, Giampietro V, Brammer MJ, Poon L, Simmons A, Williams SC, Checkley SA, Sharma T. Neural abnormalities during cognitive generation of affect in treatment-resistant depression. Biol Psychiatry. 2003 Oct 15;54(8):777-91.

Malhi GS, Lagopoulos J, Ward PB, Kumari V, Mitchell PB, Parker GB, Ivanovski B, Sachdev P. Cognitive generation of affect in bipolar depression: an fMRI study. Eur J Neurosci. 2004 Feb;19(3):741-54.

Davidson RJ, Irwin W, Anderle MJ, Kalin NH. The neural substrates of affective processing in depressed patients treated with venlafaxine. Am J Psychiatry. 2003 Jan;160(1):64-75.

ClinicalTrials.gov Identifier:	NCT00188942 History of Changes
Other Study ID Numbers:	UHN REB 04-0204-B, CTA Control #095694
Study First Received:	September 12, 2005
Last Updated:	October 18, 2006
Health Authority:	Canada: Health Canada

Keywords provided by University Health Network, Toronto:

Magnetic Resonance Imaging
Diagnostic Imaging
Mood Disorders
Bipolar Disorder

Major Depressive Disorder
Antipsychotic
Olanzapine
Fluoxetine

Additional relevant MeSH terms:

Bipolar Disorder
Depressive Disorder
Depression
Depressive Disorder, Major
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Behavioral Symptoms
Fluoxetine
Olanzapine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 09, 2012