Electroencephalography (EEG) Biomarkers of Response in Depression
Condition: Major Depressive Disorder
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 4

Summary: 
      There are two specific aims of this project:

        1. To identify physiologic indicators of venlafaxine treatment response using quantitative
           EEG (QEEG) cordance, and to determine if cordance changes are specifically associated
           with response to venlafaxine

        2. To identify predictors of placebo response in major depression using QEEG
           cordance/bispectral index (BIS) and neuropsychological testing
    

Detailed description: 
      Our previous work indicates that a combination of neurophysiologic, symptom, and cognitive
      measures may predict response more accurately than brain functional measures alone. The
      purpose of this study is to replicate results from our earlier work using a similar study
      design (96-06-291-11), and also to prospectively gather additional information to
      substantiate that a more comprehensive approach to subject assessment will yield more
      accurate and reproducible prediction of treatment response.

      One of the major challenges involved in clinical trials for major depressive disorder (MDD)
      is that of placebo response. The placebo response rate has been estimated at 20 - 50% of
      those subjects who enter a standard clinical trial for MDD. This high rate of response to
      placebo, which may not differ substantially from the response rate to medication, can make it
      difficult to demonstrate the efficacy of new antidepressant compounds. Identification of MDD
      subjects with a placebo responder (PR) phenotype, either at the beginning or end of a
      clinical trial, could have two major potential benefits. First, identification of placebo
      responders prior to enrollment in a clinical trial might make it possible to have restrictive
      entry criteria, excluding such subjects from the trial. Segregation of PR phenotype subjects
      a priori could reduce variance in the outcome data and increase the drug-placebo difference.
      This exclusion could reduce the number of subjects required for clinical trials and render
      the trials more efficient. Second, identification of a PR phenotype during a clinical trial
      could make it possible to distinguish "true medication" from placebo response. This
      distinction could make it possible to identify subgroups in the trial, enhancing precision in
      the study of medication effects.

      Our research group has performed a series of placebo-controlled treatment trials in MDD and
      has used a combination of behavioral ratings, self-report, and neurophysiologic measurements
      with quantitative electroencephalography (QEEG) to identify predictors of both placebo
      response and medication response. The preliminary results from previous studies suggest that
      a combination of neurophysiologic, symptom, and cognitive measures may be useful for
      pretreatment prediction and/or early treatment detection of different types of treatment
      response.

      In this study our primary goal is to assess the neurophysiologic, behavioral, and cognitive
      assessments of subjects with MDD in the setting of a clinical trial to replicate
      prospectively these initial results and more completely identify the characteristics of
      different types of treatment response in a clinical trial.
    

Intervention name(s): venlafaxine (Effexor); placebo
Intervention type(s): Drug; Drug
Intervention description(s): Matching capsules containing venlafaxine 37.5 mg. WERE prepared by the UCLA Pharmacy for the initial phase of the study. After a one-week placebo lead-in, subjects WERE randomly assigned to receive one capsule of either venlafaxine or placebo, with the dosage increase every two days until subjects received four capsules daily (subjects achieved a dose of 150 mg. of venlafaxine after 10 days). The first dose was administered in the morning, with subsequent capsules added on a b.i.d. schedule.; Matching capsules containing placebo 37.5 mg. WERE prepared by the UCLA Pharmacy for the initial phase of the study. After a one-week placebo lead-in, subjects WERE randomly assigned to receive one capsule of either venlafaxine or placebo, with the dosage increase every two days until subjects received four capsules daily (subjects achieved a dose of 150 mg. of venlafaxine after 10 days). The first dose was administered in the morning, with subsequent capsules added on a b.i.d. schedule.
Intervention MeSH terms: Venlafaxine Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: mdd; major depressive disorder; depression