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

NCT00634283 | Completed Phase 4 Results

• 1 other identifier: 07-10-051
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Depression

Outcome Measures

Primary Outcomes (2)

• Changes in Quantitative Electroencephalogram (qEEG) Prefrontal Cordance (PFC) Over Time (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.

  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

Study Arms (2)

antidepressant-experienced

EXPERIMENTAL

Subjects who had previously been exposed to active antidepressant medication (venlafaxine)

Drug: venlafaxine

antidepressant-naive

PLACEBO COMPARATOR

Subjects who had previously been exposed to placebo only (and never to active antidepressant medication)

Drug: venlafaxine

Interventions

venlafaxine DRUG

venlafaxine IR 150mg

Also known as: Effexor

antidepressant-experienced; antidepressant-naive

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

University of California Los Angeles (UCLA)

Los Angeles, California, 90024, United States

Location

Related Publications (1)

• Hunter AM, Cook IA, Abrams M, Leuchter AF. Neurophysiologic effects of repeated exposure to antidepressant medication: are brain functional changes during antidepressant administration influenced by learning processes? Med Hypotheses. 2013 Dec;81(6):1004-11. doi: 10.1016/j.mehy.2013.09.016. Epub 2013 Sep 17.

  PMID: 24112999 RESULT

MeSH Terms

Conditions

Depression

Interventions

Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Results Point of Contact

• Title: Director of the Laboratory of Brain
• Organization: Laboratory of Brain, Behavior, and Pharmacology at UCLA

info@brain.ucla.edu

310-825-0207

Study Officials

• Andrew Leuchter, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: We compared EEG outcomes for those subjects who had been randomly assigned to blinded treatment with venlafaxine (antidepressant-experienced, n=2) vs. placebo (antidepressant-naive, n=4). All subjects received 1 week of placebo followed by 4 weeks of venlafaxine. Subjects were blinded to the treatment during both phases of the study using lookalike capsules. Outcomes assessors and the treating physician also were blinded to treatment condition.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Subjects are assigned to one of two groups (antidepressant-experienced and antidepressant-naive) and receive parallel treatment (1 week of placebo followed by 4 weeks of venlafaxine) for the duration of the study. Subjects and assessors were blinded to treatment condition.

Study Record Dates

• First Submitted: March 6, 2008
• First Posted: March 13, 2008
• Study Start: February 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: March 9, 2020
• Results First Posted: February 18, 2020

Record last verified: 2020-02

Locations

US (1)