Major Depressive Disorder Clinical Trial
Official title:
Neurophysiologic Monitoring of Antidepressant Treatment
The overall goal of this proposal is to study quantitative electroencephalography (QEEG ) as a method for the detection of antidepressant treatment response. The investigators have developed a QEEG algorithm called "cordance" that appears to provide much the same information about brain function as PET or SPECT scanning, and has shown patterns of brain function that appear to be indicative of depression. Of greatest interest is that these patterns appear to normalize in response to antidepressant treatment.
Background and Significance/Preliminary Studies:
A. Cordance. There is considerable evidence indicating that abnormal slow-wave activity in
the EEG is caused by partial cortical deafferentation. Despite this fact, no clinically
relevant measure of deafferentation has been available. The investigators sought to develop
such a measure by examining young and old subjects with white-matter lesions that presumably
undercut the cerebral cortex, as well as subjects with several different types of brain
disease who had undergone SPECT scanning. The investigators discovered an indicator termed
discordance, that is characteristic of cortex undercut by white-matter lesions, or that is
hypoperfused for any reason. The investigators also discovered an indicator the
investigators termed concordance , which is characteristic of cortex that has normal
perfusion.
This overall technique for the non-invasive assessment of afferent function, cerebral
perfusion, and metabolism the investigators call cordance mapping, which is the subject of a
United States patent. A detailed explanation of the formulae used to calculate cordance is
provided in the manuscripts referenced above. The first of these two manuscripts contains
illustrative examples where discordance was useful in detection of white-matter lesions or
degenerative disease. The second manuscript shows a quantitative analysis of cordance and
HMPAO-SPECT data from 27 patients with a variety of conditions, and demonstrates that
cordance is superior to conventional EEG measures in its correlations with relative
perfusion. Like SPECT, cordance measurements vary according to the patients' state, but has
high test-retest reliability for detecting brain lesions.
B. Differential diagnosis of depression. One promising application of cordance is to the
differential diagnosis of psychiatric illness. A "normal" cordance pattern is one of
posterior dominant concordance with cordance values near zero in the frontal regions. The
investigators have reported a "classic" cordance pattern for subjects with Alzheimer's
disease (DAT), in which there is parietal discordance (in the beta or theta bands) in
conjunction with alpha concordance that has shifted from the occipital to the central head
regions. This finding is consistent with the pattern seen commonly on PET and SPECT, in
which there is parietal hypoperfusion or hypometabolism with preserved metabolism over the
central head regions (the motor strip), which is known to be less affected by Alzheimer's
changes.
In evaluating treatment results, the investigators will need to determine what effect
medication status has upon QEEG measures. Although results thus far suggest that there is
little significant effect , the investigators will carefully examine the effects of
antidepressant and antianxiety medications further
METHODS:
The investigators plan to examine cordance in 26 subjects undergoing antidepressant
treatment, and to use this neurophysiologic method to assess the response to treatment in
depressed patients. The project has the following three specific aims: 1) to identify
physiologic indices of fluoxetine treatment response using quantitative EEG; 2) to detect
how early in the course of fluoxetine treatment response this response may be detected; 3)
to determine if QEEG measures of response distinguish subjects who are not responding to
treatment from those who are responding.
The study will tests the hypothesis that those subjects receiving active treatment who show
clinical improvement will demonstrate normalization of cordance maps. Conversely, the
investigators hypothesize that those subjects who either do not show improvement, or who
have some improvement on placebo, will not show normalization of cordance.
The investigators will examine these hypotheses with a four-step plan. Specifically, the
investigators will recruit 26 patients with major depression and perform baseline
assessments of the severity of depressive symptoms, as well as QEEG studies. Second, the
investigators will enroll these patients in an eight-week, double-blind placebo-controlled
study in which they will receive either fluoxetine 20 mg. daily or placebo. Third, the
investigators will follow subjects with ratings of mood and serial QEEG studies to determine
if there is an association between resolution of depressive symptoms and QEEG cordance
changes. Fourth, the investigators will enroll subjects in open-label treatment at the end
of the eight weeks and examine cordance in those who previously received placebo and, where
appropriate, in those receiving fluoxetine 40 mg. daily.
;
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
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