Clinical trial NCT00188942: A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder
Official title: Neural Correlates of Emotional Processing in Depressed and Remitted Bipolar and Unipolar Depressed Subjects: An fMRI Investigation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: Magnetic Resonance Imaging
Diagnostic Imaging
Mood Disorders
Major Depressive Disorder
Antipsychotic
Olanzapine
Fluoxetine
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2005-09-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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 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.

Primary outcomes:
measure: MRI Data - Acquired before and 1- 3- and 6- weeks after beginning pharmacotherapy.
timeFrame: 6 weeks
measure: 17 Item - Hamilton Depression Rating Scale - Weekly
timeFrame: 6 weeks
measure: Clinical Global Impression - Improvement/Severity - Weekly
timeFrame: 6 weeks
measure: Young Mania Rating Scale - Weekly
timeFrame: 6 weeks
Secondary outcomes:
measure: Positive Affect Negative Affect Scale
timeFrame: 6 weeks
measure: Beck Depression Inventory
timeFrame: 6 weeks
measure: State Trait Anxiety Index
timeFrame: 6 weeks
measure: Behavioural Activation/Inhibition Scale
timeFrame: 6 weeks
measure: SexFX Scale
timeFrame: 6 weeks
measure: AMDP-5 Symptom Questionnaire
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network - Toronto General Division
state: Ontario
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Division
state: Ontario
Study officials:
affiliation: University Health Network, Department of Psychiatry, University of Toronto
name: Sidney H. Kennedy, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1016/s0006-3223(02)01785-7.
citation: 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. doi: 10.1111/j.0953-816x.2003.03159.x.
citation: 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. doi: 10.1176/appi.ajp.160.1.64.