Study of the Effects of an Antidepressant Medication and Placebo on the Brain Functioning of Normal Subjects

February 26, 2020 updated by: Andrew F. Leuchter, University of California, Los Angeles

Physiologic Monitoring of Antidepressant Medication Effects in Normal Healthy Subjects II

This study examines the effects of an antidepressant medication and placebo on the brain functioning of normal subjects. In this study, recordings of brain electrical activity are being used to detect and monitor the response to treatment with venlafaxine IR (Effexor), a drug used for the treatment of depression. The intent of this study is to test specific hypotheses regarding:

  1. long-term brain effects of a single course of antidepressant treatment
  2. pharmaco-conditioning effects underlying antidepressant tolerance/sensitization
  3. brain functional response to initial versus subsequent antidepressant trials in normal healthy subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Major Depressive Disorder (MDD) is a lifelong and recurrent illness, such that many individuals require multiple courses of antidepressant medication treatment. While some patients respond completely to each course of treatment, many do not, and with each unsuccessful antidepressant trial the likelihood that a patient will respond decreases. This raises the possibility that neurophysiologic response in subsequent antidepressant treatment may be influenced by learning processes including sensitization, habituation, and/or classical conditioning. Classical conditioning would entail the association of cues such as pill-taking (conditioned stimuli; CS) with the effects of active medication (unconditioned stimulus; US), such that later presentation of the CS alone would come to elicit a conditioned response (CR). Such effects could be revealed by blinded administration of placebo following a period of treatment with active medication. Habituation effects (tolerance), or sensitization effects (increased response), which require only repeated exposure to a stimulus, might be evidenced after repeated courses of antidepressant treatment. Knowledge of how learning processes impact neurophysiologic response to successive courses of antidepressant treatment would have relevance for clinical populations. Specific hypotheses, however, may be tested in healthy non-clinical samples to avoid potential confounding factors related to severity or chronicity of illness. Learning theories would suggest two hypotheses: (1) neurophysiologic response to placebo will differ between subjects who were previously treated with antidepressant treatment as compared to placebo (classical conditioning hypothesis); and (2) neurophysiologic response to an initial course of antidepressant treatment will differ from response to a repeated course of antidepressant treatment.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90024
        • University of California Los Angeles (UCLA)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject age is 18-75 years
  • Subject must be in overall good health (i.e., free of any medical condition known to affect brain function).
  • Subject must have participated in former study, Physiologic Monitoring of Antidepressant Medication Effects in Normal Controls Subjects (IRB#: 00-11-038-13)
  • Subject has had a normal physical exam within one year prior to entry of the study
  • Capacity to give Informed Consent

Exclusion Criteria:

  • Subject has serious medical illness, such as high blood pressure, heart disease, renal impairment, or cirrhosis of the liver.
  • Subject meets DSM-IV Axis I criteria for a mood, anxiety, cognitive, or psychiatric disorder; or meets criteria for cluster A or B axis II diagnoses. These disorders will be determined on the basis of a structured assessment with the MINI (Mini International Neuropsychiatric Interview for DSM-IV Axis I Disorders)
  • Subject has a history of current or past active suicidal ideation or suicide attempts.
  • Subject has received treatment with an antidepressant medication or any medications that could influence brain function since his/her participation in the initial study
  • Subject is using any of the following medications which interfere with EEG measures of brain function: Anticholinergics, Barbiturates, Benzodiazepines, Sedating Antihistamines (e.g. diphenhydramine (Benadryl) would be exclusionary, but not loratadine (Claritin))
  • Subject has a history of seizures, brain surgery, skull fracture, significant head trauma, or previous abnormal EEG
  • Subject is pregnant or planning on becoming pregnancy during course of the study
  • Subject is a UCLA student or staff member directly under instruction or employment of any of the investigators

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: antidepressant-experienced
Subjects who had previously been exposed to active antidepressant medication (venlafaxine)
Drug: venlafaxine
venlafaxine IR 150mg
Other Names:
  • Effexor
Placebo Comparator: antidepressant-naive
Subjects who had previously been exposed to placebo only (and never to active antidepressant medication)
Drug: venlafaxine
venlafaxine IR 150mg
Other Names:
  • Effexor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over Time (4 Weeks).
Time Frame: Average over 4 weeks
Cordance values were calculated from conventional 'absolute' and 'relative' qEEG power measures using a three-step procedure. First, EEG power values were computed using a re-attributional electrode montage. Second, the absolute and relative power values were z-transformed to measure deviation from the mean values for each electrode site s in each frequency band f for that recording, yielding Anorm(s,f) and Rnorm(s,f), respectively. Third, these z-scores were summed to yield a cordance "intensity" value, Z, for each electrode in each frequency band where Z(s,f) = Anorm(s,f) + Rnorm(s,f). Analyses for this report focused on changes-from-baseline theta-band (8-12Hz) cordance in the prefrontal region (electrodes Fp1, Fpz, Fp2). Results are defined in terms of positive and negative change where a positive change represents an increased physiologic and behavioral response to the drug (sensitization) and a negative change represents an increased tolerance to the drug (habituation).
Average over 4 weeks
Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over 1 Week Placebo lead-in.
Time Frame: 1-week placebo lead-in
Cordance values were calculated from conventional 'absolute' and 'relative' qEEG power measures using a three-step procedure. First, EEG power values were computed using a re-attributional electrode montage. Second, the absolute and relative power values were z-transformed to measure deviation from the mean values for each electrode site s in each frequency band f for that recording, yielding Anorm(s,f) and Rnorm(s,f), respectively. Third, these z-scores were summed to yield a cordance "intensity" value, Z, for each electrode in each frequency band where Z(s,f) = Anorm(s,f) + Rnorm(s,f). Analyses for this report focused on changes-from-baseline theta-band (8-12Hz) cordance in the prefrontal region (electrodes Fp1, Fpz, Fp2). Results are defined in terms of positive and negative change where a positive change represents an increased physiologic and behavioral response to the drug (sensitization) and a negative change represents an increased tolerance to the drug (habituation).
1-week placebo lead-in

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

March 6, 2008

First Submitted That Met QC Criteria

March 6, 2008

First Posted (Estimate)

March 13, 2008

Study Record Updates

Last Update Posted (Actual)

March 9, 2020

Last Update Submitted That Met QC Criteria

February 26, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-10-051

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Depression

Clinical Trials on venlafaxine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Montenegro

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe