Deep Brain Stimulation of the Amygdala for Combat Post-Traumatic Stress Disorder

Inclusion Criteria:

- Male aged 25-70 years.

- Able to give informed consent in accordance with institutional policies and
participate in the 2-year follow-up, involving assessments and stimulator adjustments.

- Patients must be stable on their current psychotropic medication for a period of 2
months before implantation and agree to not increase dosages or add any new
medications for the first 6 months of the study, unless medically necessary.

- Chart diagnosis of chronic and treatment-refractory PTSD as the principal psychiatric
diagnosis and cause of distress and social/occupational impairment.

- Confirmation of PTSD as the primary psychiatric diagnosis by the study psychiatrist
via clinical interview and CAPS.

- Confirmation of combat trauma exposure via military record review and a Combat
Exposure Scale score > 9.

- Minimum 5 year total illness duration, with no 6 month period of clinical remission
during the 5 years prior to entry in the study.

- Clinical record documentation of non-response to at least 2 of the following
antidepressants, alone or in combination, at maximally tolerated FDA recommended doses
for ≥ 6 months: sertraline, paroxetine, fluoxetine, citalopram, escitalopram,
amitriptyline, imipramine, nortriptyline, desipramine, clomipramine, phenelzine,
tranylcypromine, venlafaxine, mirtazapine. Antidepressant trials must include at least
one SSRI and one SNRI or TCA at maximally tolerated FDA recommended doses for a
minimum of 3 months.

- A minimum 3 month trial of prazosin at 10 mg per day or, if less, maximally tolerated
FDA recommended doses, unless considered contraindicated based on co-morbid medical
conditions or concomitant medications.

- Trial of at least 3 months of one of the following: lithium, divalproex sodium,
carbamazepine, lamotrigine, olanzapine, risperidone, bupropion either alone or in
conjunction with one or more of the agents in #8 and # 9 above.

- 6 months of continuous individual psychotherapy, conducted at least twice monthly for
minimum 45 minute sessions, and consisting of a) clinician- defined
cognitive-behavioural psychotherapy directed toward reducing conditioned fear symptoms
of PTSD; b) cognitive processing psychotherapy for PTSD; c) prolonged exposure therapy
for PTSD (imaginal, in vivo, and/or virtual reality); or d) Eye movement
desensitization and reprocessing therapy for PTSD including a trauma exposure
component, with chart documentation of inadequate benefit despite concerted effort.
Other forms of individual or group psychotherapy are permitted but not required for
inclusion. (Patients who are unable to complete 6 months of psychotherapy may be
included if the cause of treatment cessation was that the risks of further treatment,
including intense psychological suffering, outweighed the potential benefits of
continuing the treatment).

- All evidence based psychotherapy for PTSD (cognitive behavioural, cognitive
processing, prolonged exposure, eye movement desensitization) has been completed a
minimum of 3 months prior to enrolment.

- Minimum baseline CAPS17 of 85 at entry, with a) scores of at least 4 (combined
frequency and severity) on at least one symptom from each cluster (intrusion,
avoidance and hyperarousal); b) score of 5 or more on CAPS17 items 4 or 5 (intense
psychological distress or physiological reactivity on exposure to a reminder of the
traumatic event); and c) no questionable validity (QV) rating greater than 1 on any
CAPS item.

- Clinically significant impairment in occupational functioning due to PTSD, manifested
by one or more of the following: a) Total federal (service connected ≥ 70%), or State
(SSI) disability compensation for at least the past 2 years for PTSD; b) global
assessment of functioning score ≤ 45; c) no period of full time gainful employment ≥ 3
months in the past 5 years.

- Clinically significant impairment in social functioning due to PTSD, manifested by one
or more of the following: a) little or no social activity outside the household other
than as necessary for medical appointments, practical matters such as grocery
shopping, or to interact with other veterans; b) reliable description by a spouse or
significant other, living with the patient, of repeated avoidance/refusal to
participate in customary social engagements with friends, family or for recreational
activities due to PTSD; c) two or more verbal or physical interpersonal altercations
within the past year requiring another person's intervention to prevent further
escalation, or involving law enforcement

- Cohabitation with a spouse or significant other adult person who a) can confirm the
symptoms and impairment from PTSD and lack of significant symptomatic remission in the
past 5 years; and b) is willing to participate with the study psychiatrist in
answering questions for the life functioning in PTSD scale (LFIPS) at scheduled
follow-up visits; and c) is willing to report unexpected adverse neurological or
psychiatric events to study investigators and if advised by study investigators,
assist the patient in accessing necessary services to address these.

- Willingness to have unexpected neurological or psychiatric symptom shared with the
study psychiatrists and other study clinicians.

- Other medical conditions must be stable for at least 1 year, (conditions that require
intermittent use of steroids or chemotherapy are excluded).

Exclusion Criteria:

- Suicide attempt in the last 2 years and/or presence of a suicide plan (an answer of
"Yes" to Question C4 in Section C-Suicidality of MINI International Neuropsychiatric
Interview);

- Psychosis or bipolar disorder; significant acute or ongoing risk for violence;

- Patients primarily diagnosed with DSM-IV-TR Axis I disorder other than PTSD as
determined by the MINI;

- Within the 3 months prior to enrolment, subject has started a new psychotherapy
program;

- Alcohol or illicit substance use disorder within the last 6 months, unstable remission
of substance abuse, or chart evidence that co-morbid substance use disorder could
account for lack of treatment response;

- Current significant neurological conditions, including epilepsy, stroke, movement
disorder; history of serious head injury with loss of consciousness

- Patients with uncontrolled medical conditions (hypertension, diabetes, infection);

- Uncontrolled chronic pain;

- Baseline Montgomery Asberg Depression Rating Scale (MADRS) of ≥ 28;

- Patients who are receiving anticoagulation therapy;

- Significant abnormality on preoperative structural brain MRI;

- ECT in the past 6 months;

- Contraindications to MRIs or the need for recurrent body MRIs;

- Immunosuppression;

- Patients who are not appropriate candidate for general anesthesia and/or DBS surgery;

- Current pursuit of new or increased disability compensation for PTSD;

- Has cardiac pacemaker/defibrillator, implanted medication pump, intra- cardiac lines,
any intracranial implants (aneurysm clip, shunt, cochlear implant, electrodes) or
other implanted stimulator;

- Patient has had past cranial neurosurgery;

- Patient unable to discontinue therapeutic diathermy;

- Use of other investigational drugs or psychotropic herbs within 30 days of baseline.

- Patients suffering from a neurovascular condition or other intracranial process.

- Patients suffering from a condition associated with a significant cognitive
impairment.