Adapted Cognitive Behavioral Treatment for Depression in Patients With Moderate to Severe Traumatic Brain Injury

The primary aim of this study is to develop a highly acceptable, manualized treatment
(CBTx-TBI) for MDD in patients with moderate to severe TBI. After developing the manual
(Phase 1), a nonrandomized trial (Phase 2) will be conducted to test its acceptability and
tolerability. Based on objective and qualitative feedback from participants and input from
mentors and consultants, the CBTx-TBI manual will be revised (Phase 3). The investigators
will then pilot test the efficacy of the intervention to reduce depressive symptoms (IDS-C)
after 12 weeks using the revised CBTx-TBI manual compared to a waitlist control group in a
randomized pilot trial (Phase 4). Once the randomized pilot study is complete, the CBTx-TBI
manual will be finalized with additional feedback from subjects, mentors, and therapists.

For both phases of recruitment, the same study procedures will be used (unless procedures are
modified in Phase 3). The proposed study involves the following points of contact: (1)
Obtaining informed consent and screening (may be broken up into multiple visits), (2)
biweekly clinician assessments of depressive and neuropsychiatric symptoms (weeks 2, 4, 6, 8,
10), (3) weekly self-report assessments of depressive symptoms for those receiving the
intervention, (4) 12 weekly individual CBTx-TBI sessions for those randomized to the
intervention, (5) a comprehensive assessment at week 12 (primary endpoint), which includes
the neuropsychological battery, and (6) a 3-month follow-up assessment for those who received
the intervention (randomized pilot only, phase 4). Assessment visits during the 12 weeks of
treatment may be completed by phone. The week 12 visit can be split into two parts, with the
neuropsychological assessment occurring during the second part, in order to accommodate
subjects' potential limitations due to fatigue.

Inclusion Criteria:

1. Adults aged 18 to 65, inclusive

2. English language proficiency

3. Ability to provide written, informed consent; OR consent provided by legally
authorized representative with assent from subject

4. Ability to see and hear (hearing or visual loss cannot impair ADLs or in-room
conversation)

5. Ability to attend in-person, outpatient sessions

6. Having been hospitalized for moderate to severe TBI that occurred at least 3 months
prior to study entry

7. Meeting ANY ONE of the following severity criteria, as documented in electronic
medical record (EPIC) or available outside records:

1. GCS 3-12 with GCS motor score ≤ 5 within 4 hours after injury

2. GCS 3-12 with GCS motor score =6 within 4 hours after injury AND documented
intracranial abnormalities on imaging

3. GCS 13-15 within 4 hours after injury AND documented intracranial abnormalities
on imaging

4. Loss of consciousness (LOC) > 30 min.

5. Post-traumatic amnesia (PTA) > 24 hours

8. Out of PTA at the time of enrollment (GOAT>75)

9. Current Major Depressive Episode as assessed by the MINI

10. If taking medication for depression, must have been on stable dose for 4 weeks prior
to study entry and no changes during the study.

Exclusion Criteria:

1. Uncontrolled medical illness

2. Behavioral dyscontrol, defined as the presence of verbally or physically aggressive
behavior in the past month, as evidenced in medical records, pre-screening interviews,
or observed by any study staff

3. Presents with PTSD as the primary diagnosis, as determined by a clinician

4. Substance abuse or dependence within the past six months

5. Has bipolar disorder, a primary psychotic disorder or current psychotic symptoms, or
acute suicidality or homicidality

6. Currently receiving regular (≥ 2 times/ mo.) psychosocial treatment for depression

7. Has participated in CBT for depression within the past 6 months