Treatment of Post-Traumatic Brain Injury (TBI) Depression

Purpose: The purpose of this study is to document the efficacy of sertraline (Zoloft) in the
treatment of depression (major depressive disorder) after TBI, including the impact on
quality of life. Researchers will also explore the effects of sertraline on anxiety
disorders, which often accompany post-TBI depression.

Background: Major depression is experienced by many more people after TBI than prior to
injury and more often than in people without a brain injury. Many studies have also shown
that this higher than 'normal' incidence looms for many years post TBI. Major depression is
associated with a variety of negative outcomes, including poorer functioning in basic
activities, reduced employment, elevated divorce rate, reduced social and recreational
activity and increased sexual dysfunction.

Need for Research: Of the current drug treatments for major depression, sertraline and
similar drugs (known as selective serotonin reuptake inhibitors, or selective serotonin
reuptake inhibitor (SSRIs)) have few side effects in people who have experienced a brain
injury and have been shown to be effective in people with no known brain injury. However,
information on the impact of SSRIs on post-TBI depression, based on randomized, double-blind
studies, is unavailable.

Current Research Activity: Approximately 50 men and women volunteers who are post TBI and
currently diagnosed with major depressive disorder are being randomly assigned to a 12-week
period of taking Zoloft or a placebo. Over the period of study, participants will have the
severity of their depressive symptoms assessed (as well as their symptoms of anxiety); a
simple measure of the volunteer's perceived quality of life will be implemented prior to the
study and at its termination. It is hypothesized that sertraline will reduce the symptoms of
depression and anxiety and will increase the person's perceived quality of life to a
significantly greater extent than will the placebo.

Inclusion Criteria:

- 18 years or older

- experienced a TBI with a documented loss of consciousness or other evidence of a TBI
(i.e., evidence of pathology on neuro-imaging)

- at least 6 months post-injury

- English-speaking

- residential telephone service

- living within 1.5 hours of New York City

- able to comprehend or answer verbal or written questionnaires

- willing to provide consent to participate in a 12 week drug study to treat Major
Depressive Disorder (MDD); current MDD as diagnosed using Structured Clinical
Interview for Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)
Disorders (SCID), and severity of MDD rated at least 18 on the HAM-D.

Exclusion Criteria:

- currently taking antidepressant medication (including monamine oxidase inhibitors
(MOAs) or tricyclic antidepressants (TCAs)

- unwilling to abstain from seeking new psychosocial or pharmacologic treatments during
the course of the study

- currently in psychotherapy

- active suicidal plans and/or requiring hospitalization

- prior use of sertraline

- currently experiencing other serious medical illness

- currently pregnant or breast feeding

- mass brain lesions or other neurological diagnoses other than TBI

- history of current or past psychosis or mania

- current substance abuse

- history of clinically significant liver or renal disease