The Effect on Cognition of Terminating ECT Induced Seizures With Propofol

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.

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