Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism

NCT00704860 | Completed Phase 4

• 1 other identifier: REB- 200506
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Reduction of volume of the hippocampus has been associated with major depression in many studies. It has been suggested that antidepressants may protect against hippocampus volume loss in humans associated with multiple episodes of depression and may also reverse the reduction of volume caused by the depression. In addition, genetic markers for serotonin are implicated with depression, and may be an indication of reduced response to antidepressant treatments. This study aims to enroll patients who are defined as having treatment resistant depression (no remission after at least 2 treatments trials with an antidepressant). They will receive an MRI scan at the initial visit and either 6 months after sustained remission or 12 months after they enter the study for non-remitters. They will also be asked to give a blood sample for genotyping. They will be matched by age and handedness to healthy volunteers with no personal history of depression who will also receive an MRI scan and genotyping. The first aim is to compare hippocampal volume of depressed subjects to healthy controls. It is anticipated that subjects will initially have smaller hippocampal volume but of those who sustain remission, there will be a small increase in hippocampal volume. It is also anticipated that specific genetic markers will be related to individuals response to antidepressant treatments.

Conditions

Major Depression

Keywords

healthy volunteers treatment resistant major depression hippocampus atrophy MRI serotonin genotyping

Outcome Measures

Primary Outcomes (1)

• Sustained Remission from Depression and Hippocampal Atrophy

  6 months

Secondary Outcomes (1)

• 5-HT1a Genetic Markers

  Baseline Visit

Study Arms (1)

TR

EXPERIMENTAL

TR- Subjects defined as having treatment resistant depression, who have failed at least 2 adequate trials of an antidepressant. Subjects will be treated in an open label trial for their depression, with the goal of sustained remission.

Other: Open label pharmacotherapy

Interventions

Open label pharmacotherapy OTHER

Dosage and drug types change based on patients need and response. doxepin, clomipramine, amoxapine, amitriptyline, maprotiline, desipramine, nortriptyline, trimipramine, imipramine, protriptyline, isocarboxazid, phenelzine, tranylcypromine, moclobemide, fluvoxamine, paroxetine, fluoxetine, sertraline, citalopram, escitalopram, venlafaxine, atomoxetine, pramipexole, bromocriptine, quetiapine, clozapine, olanzapine, ziprasidone, aripiprazole, paliperidone, Risperidone, bupropion, mirtazapine, pindolol, topiramate, trazodone, Lithium,

Also known as: All classes of antidepressants, based on patient need

TR

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between ages of 18 to 65 years of age.
• A diagnosis of Major Depression according to the DSM-IV criteria
• Failing to achieve remission while receiving at least two different antidepressants at adequate dosage for at least 6 weeks.
• Initial score of at least 18 on the HAMD-17 item rating scale

You may not qualify if:

• A diagnosis of substance abuse or dependence in the last 6 months or a lifetime diagnosis of substance abuse according to the DSM-IV criteria, elicited by inquiry.
• A diagnosis of post-traumatic stress disorder, schizophrenia, schizo-affective disorder and other psychotic disorders, anorexia nervosa or a history of a manic or mixed episode
• Major medical illnesses including endocrine and neurological disorders, as well as a history of significant head trauma
• Exposure to oral or intravenous steroids
• Contraindications to magnetic resonance imaging
• An IQ less than 80

Sponsors & Collaborators

• University of Ottawa: lead

Study Sites (1)

University of Ottawa Institute of Mental Health Research

Ottawa, Ontario, K1Z 7K4, Canada

Location

Related Links

• University of Ottawa Institute of Mental Health research homepage

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Pierre M Blier, MD, Ph.D

  University of Ottawa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 18, 2008
• First Posted: June 25, 2008
• Study Start: February 1, 2005
• Primary Completion: November 1, 2009
• Study Completion: December 1, 2010
• Last Updated: January 19, 2011

Record last verified: 2009-02

Locations

CA (1)