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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00634283
Recruitment Status : Completed
First Posted : March 13, 2008
Results First Posted : February 18, 2020
Last Update Posted : March 9, 2020
Sponsor:
Information provided by (Responsible Party):
Andrew F. Leuchter, University of California, Los Angeles

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. 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.

Condition or disease Intervention/treatment Phase
Depression Drug: venlafaxine Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Other
Official Title: Physiologic Monitoring of Antidepressant Medication Effects in Normal Healthy Subjects II
Study Start Date : February 2008
Actual Primary Completion Date : February 2009
Actual Study Completion Date : February 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants

Arm Intervention/treatment
Experimental: antidepressant-experienced
Subjects who had previously been exposed to active antidepressant medication (venlafaxine)
Drug: venlafaxine
venlafaxine IR 150mg
Other Name: 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 Name: Effexor




Primary Outcome Measures :
  1. 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).

  2. 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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00634283


Locations
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United States, California
University of California Los Angeles (UCLA)
Los Angeles, California, United States, 90024
Sponsors and Collaborators
University of California, Los Angeles
Investigators
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Principal Investigator: Andrew Leuchter, MD University of California, Los Angeles
Publications of Results:
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Responsible Party: Andrew F. Leuchter, Principal Investigator, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00634283    
Other Study ID Numbers: 07-10-051
First Posted: March 13, 2008    Key Record Dates
Results First Posted: February 18, 2020
Last Update Posted: March 9, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
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Depression
Behavioral Symptoms
Venlafaxine Hydrochloride
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs