Pharmacological Intervention in Depression After Traumatic Brain Injury

The study evaluates the benefits of a promising antidepressant medication for the treatment
of persons with traumatic brain injury (TBI) and major depressive disorder (MDD). The study
is a randomized, double-blind, placebo-controlled trial of venlafaxine (a serotonin and
norepinephrine reuptake inhibitor, also known as Effexor). Venlafaxine has been well
established in the treatment of MDD in healthy individuals and is a recommended depression
treatment agent for persons with TBI. By using a rigorous scientific methodology, this study
will be an important first step in advancing the treatment of depression in this population
beyond general impressions to proven treatments.

Inclusion Criteria:

- Must have a documented traumatic brain injury (TBI), defined as damage to brain
tissue caused by an external mechanical force as evidenced by: loss of consciousness
due to brain trauma, or post traumatic amnesia (PTA), or skull fracture, or objective
neurological findings that can be reasonably attributed to TBI on physical
examination or mental status examination.

- Age 18 years or older

- At least three months postinjury

- Presence of major depressive disorder (MDD), as defined by Structured Clinical
Interview for DSM-IV (SCID) interview

- Hamilton Depression Rating Scale (Ham-D) scores of 18 or greater on two consecutive
evaluations (screening and baseline)

Exclusion Criteria:

- Individuals under 18 years of age

- Pregnancy, as determined by urine pregnancy screen

- Prisoners

- Individuals who are institutionalized

- Individuals who are not cognitively capable of completing the SCID interview and the
Ham-D

- Unstable medical condition, defined as any significant medical condition likely to
require hospitalization during the study period, or requiring adjustment in
medications in the past month

- Active suicidality

- Severe depression that, in the investigator's professional opinion, will likely
require hospitalization during the study time period

- Diagnosis of bipolar disorder, as defined by SCID interview

- Diagnosis of schizophrenia or other psychotic disorder, as defined by SCID interview,
other than major depression with psychotic features

- Active drug or alcohol abuse within the past 3 months, as defined by SCID interview

- Dysphagia sufficient to preclude use of oral medications

- Known hypersensitivity to venlafaxine

- Use of monamine oxidase inhibitors (MAOI) within the past month

- Treatment with antidepressant medication within the past 3 months

- Concomitant administration of medications that interact with venlafaxine to a
clinically significant degree