Project to Improve Symptoms and Mood in People With Spinal Cord Injury

Depression is likely the most prevalent and disabling psychological complication associated
with spinal cord injury (SCI). The prevalence of major depression in people with SCI is 22%
or two to six times higher than in the general population. Depression is linked to a myriad
of adverse outcomes including poor subjective health, poor community integration, higher
rates of medical complications and high rates of suicide. Surprisingly there are no
randomized controlled trials for treating major depressive disorder (MMD) in people with
SCI. Despite the widespread use of antidepressants in this population, the common assumption
that antidepressant medications are effective and well-tolerated among people with SCI is
uncertain. Multiple factors such as severe stresses, bereavement and loss of rewarding
activities may complicate treatment. Treatment trials suggest antidepressants may not be as
effective in people with medical/neurological conditions as they are with depression that
develops as a primary condition. For almost 20 years clinicians and scientists have called
for controlled clinical trials of antidepressants among people with SCI in order to
establish evidence-based treatment. The proposed study is a multi-site, randomized,
double-blind, placebo controlled trial of venlafaxine XR (Effexor XR) in 168 adults with SCI
and MDD or dysthymia who are at least one month post injury. Participants aged 18-64 will be
recruited from four SCI Model System sites, the University of Washington, Rehabilitation
Institute of Chicago, University of Michigan, University of Alabama, Birmingham and Baylor
Institute for Rehabilitation, Dallas TX. The purpose of the study is to examine the efficacy
and tolerability of venlafaxine XR as a treatment for MDD. The primary outcome will be the
percent of responders (those who report at least a 50% reduction in depression severity from
baseline to the end of treatment) in the venlafaxine XR versus placebo control group using
intent-to-treat analysis. Secondary outcomes will include changes in pain, health related
quality of life and participation. A successful clinical trial could lead to more aggressive
identification and treatment of MDD as well as improved health and quality of life in this
important population.

Inclusion Criteria:

- Spinal cord injury (ASIA A-D)

- At least one month post injury

- Meets DSM IV criteria for major depression or dysthymia on the SCID

- At least moderately severe depression (PHQ-9 score >= 10)

- Within reasonable travel distance to one of the study sites

Exclusion Criteria:

- Current DSM IV alcohol or drug dependence

- History of bipolar disorder or psychosis

- History of >= 2 suicide attempts or suicide attempt with 5 years

- Current suicidal intent or plan

- Medical contraindications

- Non-English speaker

- Clinically significant cognitive/language impairment

- History of allergic reaction to venlafaxine XR or use of MAO-I with 2 weeks

- Current use of antidepressant medications (will not exclude if on low dose of a
tricyclic antidepressant or trazodone for pain, sleep, or bladder), psychotherapy for
depression, or electroconvulsive therapy

- Pregnant or lactating women or women of childbearing potential who are not willing to
use a reliable form of contraception

- Unstable medical condition, as determined by physical examination, CBC w/ platelets
(including hematocrit, hemoglobin, WBC, differential), serum chemistry panel (serum
sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose), liver
transaminases (AST, ALT), thyroid stimulating hormone (TSH), urinalysis, supine
diastolic blood pressure (SDBP) > 90 mm Hg, or near terminal illness (primary care
physician estimates that patient has < 1 year to live)

- Anticipated major surgical procedures within the 12 weeks of randomization

- Use of an investigational drug within 30 days

- Use of psychoactive medications, including corticosteroids and anticonvulsants, that
have not been at a stable dose for at least 2 weeks

- Use of anxiolytic, sedative-hypnotic, or other psychotropic drug or substance
(including St. John's Wort) within 7 days of start of double-blind treatment. If the
patient is taking a sedative deemed necessary for sleep induction or spasticity, the
dosage must have been stable for at least 2 weeks. Use of anticholinergic, low-dose
tricyclic antidepressant, GABAergic or adrenergic medications for spasticity are
permitted if at a stable dose for at least 2 weeks.

- Refusal to participate