The Effect on Cognition of Terminating ECT Induced Seizures With Propofol

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. Identifier: NCT00616759
Recruitment Status : Completed
First Posted : February 15, 2008
Results First Posted : February 4, 2013
Last Update Posted : October 25, 2017
Information provided by (Responsible Party):
Loma Linda University

Brief Summary:
Participating subjects are those who are referred for electroconvulsive therapy (ECT) for severe depression who have agreed to the protocol. The control group receives ECT as usual. The other group receives propofol to terminate the ECT-induced seizure timed so that the seizure lasts at least 25 seconds. Extensive neuropsychological testing is being done on both groups before beginning ECT and within 48 hours after the 6th treatment. Multiple markers of the rapidity of recovery from anesthesia are being obtained from all subjects for 6 ECTs.

Condition or disease Intervention/treatment Phase
Major Depression Procedure: electroconvulsive therapy Procedure: electroconvulsive therapy plus propofol Drug: propofol Not Applicable

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Detailed Description:

ECT Administration All patients will receive ECT administered using a Thymatron-System IV (Somatics, LLC , Lake Bluff, IL) ECT device, the same device used for our usual ECT. All patients will be monitored with continuous electrocardiogram (EKG) monitoring, pulse oximetry, and regular blood pressure readings from an automatic inflatable cuff on one arm. Seizure threshold will be determined at the first treatment. The subsequent treatment will be administered at 1.5 times the seizure threshold. Stimulus dose will be increased as necessary to produce a seizure of at least 20 seconds observed duration of motor activity. All patients whose seizure duration is less than 20 seconds of motor activity will be re-stimulated at the same treatment session at a 50% increase in stimulus intensity unless this occurred at the maximum stimulus charge available. All monitoring described and the titration process is part of our normal ECT routine. Electrode placement will be bilateral for all patients which is the predominate placement used for our usual patients. Patients in the standard group will receive ECT as described elsewhere (Abrams, 2001). Patients in the experimental group will receive ECT as the other group. However, approximately 15 seconds after stimulus delivery they will receive a 1 mg/kg dose of propofol intravenously in order to terminate brain seizure activity reliably, whether evident on surface EEG or not. In view of 30-60 second circulation time this will limit seizure duration to 45-75 sec, and generally to the same duration at each session because the circulation time is an individual characteristic.

Routine anesthetic agents will include hyperventilation with 100% oxygen by mask, and initial dosages of succinylcholine 1 mg/kg IV, and etomidate 0.2 mg/kg IV, adjusted as needed over the treatment course. Atropine 0.4-1.0 mg will also be given intravenously before the anesthetic agent. Blood pressure and pulse will be assessed prior to treatment and 1 minute, 3 minutes, and 5 minutes following the ECT stimulus and periodically thereafter. All patients will receive at least 6 index ECT. Those needing additional treatment will receive standard ECT. Propofol and etomidate are used for our normal ECT treatments as well as atropine and succinylcholine. Blood pressure monitoring is also a part of routine ECT.

Electroencephalogram (EEG) Recording and Computer EEG Analysis Four channels of EEG data will be recorded using bilateral frontal-mastoid and bilateral frontal-occipital electrodes. Frontal and mastoid recording electrodes used will be EEG/EMG/ECG Adherent Recording Electrodes. (Somatics, LLC.) Occipital electrodes used will be Grass 10mm gold electrode. Preparation of the occipital area may include using Lemon Prep Skin Prep (Mavidon Medical LP-0019), Elefix conductive paste (Niho Kohden America, Inc.). Nu Prep Cover Roll stretch (BSN Medical) will be cut to facilitate the covering of electrodes. Analysis of some parameters of each seizure will be done with software provided by the manufacturer of the Thymatron system IV. Our standard ECT includes 2 channels of EEG recording using bilateral fronto-mastoid electrode placement using Adherent Recording Electrodes (Somatics, LLC) with computer analysis of channel 1.

Cognitive Assessment Cognition will be assessed using neuropsychological battery subtests which measure difficulties of retention of newly learned material (anterograde amnesia) and past events (retrograde amnesia) such as the California Verbal Learning Test (CVLT)(subtests: recognition tests A & B and long delay free recall). Wechsler Memory Scale (WMS III)(subtests: Mental Control, Logical Memory recognition, Memory Span), Trail Making A & B, Rey Auditory Verbal learning Test, and Rey Osterrieth Complex Figure Test (copy, recall and recognition trials). In addition, Hamilton Rating Scale of Depression, Clinical Global Improvement (CGI), Modified Mini Mental Status (3MSE), Autobiographical memory interview, Beck Depression Index (BDI) will be performed.

Emergence from anesthesia will be determined by measuring post-treatment reorientation time such as time to awaken, name recall, orientation to location, date and day of the week, with the time beginning at the end of stimulus application. Following awakening, patients will be asked at 1-min intervals to open their eyes and to squeeze the investigator's hand. The time from stimulation as well as the time from when the patients open their eyes to performance of the appropriate response to both commands will be noted. The same procedure will be used to identify place and date at 1-min intervals until the correct answer is given for each question. As soon as orientation occurs, we will administer a series of tests to evaluate recovery of psychomotor function, including the Trieger test (volunteers are asked to connect a series of dots), P-deletion test (volunteers are asked to select all letters "p" in a text of random letters during 180 s), and the Digit Symbol Substitution test (volunteers are asked to match numbers and symbols during 90 s) 15, 30, 45, 60, 75, and 90 min after cessation of anesthesia. These tests have been used previously to study recovery from anesthesia. At the same times patients will be asked to evaluate their "sense of clear-headedness," and "sense of energy". All assessments will be carried out by a blind investigator to the group membership of the patient. Our standard ECT utilizes the Mini Mental Status Examination before every third ECT to measure cognitive change. Cognitive testing emerging from anesthesia is not routinely done.

All subjects will receive six individual treatment sessions given 3 days per week. Investigators will be aware of the treatment parameters; however, independent raters will be blinded as to which treatment was administered.

Prior to the experimental treatment sessions, all subjects will participate in several preliminary meetings with the MD investigator and the psychologist. Each session will be used to facilitate the psychiatric screening, lab tests, psychological and neuropsychological tests in order to establish a baseline of memory functioning.

The experimental treatment sessions themselves will be supervised and facilitated by the MD investigator following the guidelines previously developed for this experimental procedure. Except for the administration of propofol or no drug at all following the administration of ECT, the treatment protocols will be exactly the same for each treatment group.

  • All treatment sessions will begin will occur between 7:00 am and 12:00 pm and take place in the Loma Linda University Medical Center-Outpatient Surgery Center.
  • Patients are instructed to not have anything to eat or drink (NPO) after midnight the night before ECT. They may take their morning blood pressure medications with a few sips of water.
  • An intravenous (IV) line will be established. EEG Monitoring electrodes, O2 saturation monitor, and foot blood pressure cuff will be put in place. Atropine 0.4-1.0 mg IV will be administered first, then etomidate 0.2 mg/kg IV. Succinylcholine 1.0mg/kg IV will be given as soon as the patient falls asleep. Sleep will be measured by the inability to arouse the patient and the loss of the lash reflex. Other medications may be used to control blood pressure, nausea, etc.
  • Patient will be masked with 100% O2 and hyperventilated
  • Approximately ninety seconds after the infusion of succinylcholine, the impedance will be checked using the Thymatron and then the stimulus is given.
  • During the first ECT session a titration procedure will be done in order to determine the lowest dose of electrical energy that will produce a seizure (seizure threshold).
  • The second ECT is set at 50% above the seizure threshold.
  • Subsequent stimulus settings are set to keep the seizure duration above 25 seconds at absolute minimum.
  • Propofol 0.5-1.0 mg/kg will be administered IV to patients in the experimental group when the seizure duration reaches 15 seconds as measured by the EEG monitor at all of the first six ECTs, including at the session during which titration is done, and at the seventh ECT in the control group.
  • Anesthesiologist will continue to mask the patient until the patient is able to adequately breathe on their own.
  • Patient will be taken to the recovery area and monitored with O2 in place until stable.
  • Time to awaken, time to name recall, place recall, and date recall will be assessed after each treatment by a rater who is blind to the treatment conditions.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect on Cognition of Terminating ECT Induced Seizures With Propofol
Study Start Date : September 2006
Actual Primary Completion Date : September 2008
Actual Study Completion Date : September 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Seizures
Drug Information available for: Propofol
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1
ECT as usual
Procedure: electroconvulsive therapy
electroconvulsive therapy as usual
Experimental: 2
ECT-induced seizures terminated with propofol
Procedure: electroconvulsive therapy plus propofol
electroconvulsive therapy identical to the comparator group except that propofol 0.5 mg/kg is given intravenously 15 seconds after the electrical stimulation at each treatment in order to terminate the ECT-induced seizure
Other Name: Diprivan
Drug: propofol
Propofol 0.5 mg/kg intravenously given 15 seconds following electrical stimulation

Primary Outcome Measures :
  1. Wechsler Memory Scale-III (WMS-III) Auditory Delayed Index [ Time Frame: Pre-tesing within 36 hours before first ECT; Post-testing within 36 hours of 6th ECT. ]
    WMS-III Auditory Delayed Index is a measure of memory functioning. The results given are the post-ECT testing results. A smaller number indicates less memory disturbance on this scale. The range of scores is between 0-140 with higher scores indicating better memory function.

Secondary Outcome Measures :
  1. California Verbal Learning Test (CVLT) [ Time Frame: Within one week pre-ECT and within 48 hours after the 6th ECT ]
    CVLT consists of a number of individual subtests of various aspects of memory. Higher scores indicate better memory function.

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Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, Text Revision (DSM-IV-TR) criteria for major depression, single episode or recurrent
  • Subjects must be over the age of 45 years
  • Subjects must be willing to receive at least six treatments of ECT, along with pre ECT lab screening and pre and post psychological and neuropsychological tests
  • The ability to read, speak and comprehend English and have the ability to complete the forms in writing
  • Must be able to give consent for treatment
  • Shorter acting benzodiazepines (aplrazolam, lorazepam) will be allowed on a prn basis but excluded 12 hours before each ECT session

Exclusion Criteria:

  • Subjects who have a history of schizophrenia, bipolar affective disorder, delusional disorder, paranoid disorder, or schizoaffective disorder, or who are exhibiting psychotic symptoms [except mood congruent depressive delusions].
  • Subjects who have a substance abuse/dependence disorder not in full remission
  • Patients with significant medical problems that may increase risk or require unusual concomitant treatment
  • Patients with significant neurological problems including seizure disorder
  • Patients with a hearing or visual impairment that would interfere with the research process
  • Patients with moderate to severe dementia. Any patient scoring less than 25 on the MMSE will have a Mattis Dementia Rating Scale-2 (DRS-2) test for dementia administered.
  • Patients known to be intolerant of propofol, etomidate, or succinylcholine, or for whom these anesthetic medications are not appropriate
  • Patients taking anticonvulsant medications such as Tegretol, Depakote, Klonopin, etc.
  • Patients on an involuntary admission status
  • Patients unable to give informed consent

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 identifier (NCT number): NCT00616759

United States, California
Loma Linda University
Loma Linda, California, United States, 92354
Sponsors and Collaborators
Loma Linda University
Principal Investigator: Ronald L Warnell, MD Loma Linda University

Publications of Results:
Responsible Party: Loma Linda University Identifier: NCT00616759     History of Changes
Other Study ID Numbers: 56164
First Posted: February 15, 2008    Key Record Dates
Results First Posted: February 4, 2013
Last Update Posted: October 25, 2017
Last Verified: October 2017

Keywords provided by Loma Linda University:
Electroconvulsive therapy

Additional relevant MeSH terms:
Depressive Disorder, Major
Behavioral Symptoms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Depressive Disorder
Mood Disorders
Mental Disorders
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General