Epidural Cortical Stimulation for Depression

Hypothesis: Severely Treatment Resistant Unipolar Depressed Subjects with EpCS of medial
prefrontal cortex will show a significant decrease in depression symptoms at 6 months
post-implant when compared to baseline and to a matched control group treated with
electroconvulsive therapy (ECT).

Method: We will enroll 5 subjects with severe refractory depression in an open trial with a 1
month placebo lead in, and for up to 1 years. We will also naturalistically follow 5 matched
control patients treated with ECT. Depressive and cognitive symptoms will be rated
periodically to assess the safety and efficacy of this procedure.

Significance: This study takes advantage of the expertise at MUSC with various
neuromodulation technologies to begin answering the crucial role of targeted cortical brain
stimulation and its potential role in treatment resistant depression. This is a crucial pilot
study that might lead to an entire new class of therapies for depression.

Inclusion Criteria:

To be eligible for this study, a subject must meet all the following inclusion and
exclusion criteria:

- Subject has a diagnosis of chronic (≥ two years) or recurrent (multiple prior
episodes) depression and is currently experiencing a major depressive episode without
psychotic features as defined by DSM IV criteria.

- Subjects may have a diagnosis or unipolar or bipolar depressive episode.

- Subject has not had an adequate response to 4 or more adequate antidepressant
treatments in the current depressive episode according to the Antidepressant Treatment
History Form (ATHF) (Sackeim et al 1997).

- Subject must be between the ages of 21 and 80.

- Baseline HDRS 24-item ≥ 20 (both visits 1 week apart)

- Subject must be able to complete the evaluations needed for this study including the
functional imaging scans.

- Subject must have had a history of one successful course of ECT in the past.

- Subject must provide written informed consent.

- Subject is stable on all antidepressant medication for at least 4 weeks before the
baseline visit or not be taking antidepressant medication prior to entering the study.

- Subject must be able to remain on current medication schedule for the first 19 weeks
of the study.

- Subject is not on a medication known to increase the risk of cortical
stimulation-induced seizures. These include theophylline, stimulant medications,
bupropion, or supraphysiological doses of thyroid supplements.

Exclusion Criteria:

The presence of any of the following will exclude a subject from the study:

- The EpCS would (in the investigator's judgment) pose an unacceptable surgical or
medical risk for the patient (including, but not limited to: history of serious
cardiac or pulmonary problems, stroke, significant brain malformation, progressive
neurological disease, central nervous system disease or injury, history of seizure,
previous neurosurgical procedure with suspected brain tissue scarring that would
increase the risks for seizure or cervical fracture).

- Subject received general anesthetic within the last 30 days prior to enrollment (not
including ECT procedure).

- Subject currently has another investigational device or cardiac pacemaker, implantable
defibrillator, or other implantable stimulator

- Subject on anticoagulant drugs, with low platelets counts or have PT or PTT
abnormalities or other risk factors for intra-operative or post-operative bleeding

- Subject is expected to require full body magnetic resonance imaging (MRI) during the
clinical study.

- Subject is judged by the investigator to be acutely suicidal (e.g. within the 30 days
prior to the EpCS implant, the subject has made a suicide attempt or gesture or has
made specific plans or preparation to commit suicide).

- Subject has a history of schizophrenia, schizoaffective disorder, or other psychotic
disorder, active substance abuse or dependence (with the exception to caffeine and
nicotine abuse) or a current major depressive episode that includes psychotic features
(commonly referred to as psychotic depression) according to the DSM IV criteria.

- Subject with a diagnosis of dementia with a Mini-Mental State Exam (MMSE) ≤23.

- Female subjects with a positive urine pregnancy test.

- Subject with a positive urine drug screen or current alcohol or substance abuse other
than nicotine and caffeine.