Neurophysiologic Monitoring of Antidepressant Treatment
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): fluoxetine
Intervention type(s): Drug
Intervention description(s): fluoxetine 20 mg. daily
Intervention MeSH terms: Fluoxetine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: MDD; major depressive disorder; QEEG; electroencephalograph; fluoxtine; placebo