ADAPT: Addressing Depression and Pain Together

The primary aims of the study are:

1. To test the efficacy of higher-dose Venlafaxine and Problem Solving Therapy for
Depression and Pain (VEN/PST-DP) in reducing depression and pain.

2. To test the efficacy of higher-dose VEN/PST-DP in reducing back-related disability and
improving physical functioning.

Primary Hypotheses:

1. During the 14 weeks of step 2, patients receiving VEN/PST-DP, compared to those
receiving VEN/SM, will respond faster and have a higher rate of response.

2. During the 14 weeks of phase 2, patients receiving VEN/PST-DP, compared to those
receiving VEN/SM, will have better self-reported physical functioning.

Secondary Hypothesis:

3. Self-efficacy has been shown to predict treatment outcomes for both depression and
pain. We have observed that the self-efficacy for pain management of these patients
improves with antidepressant pharmacotherapy. We hypothesize that for subjects assigned
to receive treatment with VEN/PST-DP, self-efficacy will mediate treatment response.

Inclusion Criteria:

1. Age 60 or older

2. Scores 10 or higher on the Patient Health Questionnaire-9 (PHQ-9). This is consistent
with at least moderate depression severity.

3. Endorses low back pain more days than not, of at least moderate severity, for at
least the past 3 months.

4. If venlafaxine up to 150 mg/day has been tried for at least 6 weeks, subjects must
have been *completely* unresponsive for both depression and low back pain (based on
subject report).

5. During this episode of CLBP, must have tried without continued success any of the
following: 1) prescription or over the counter analgesics, 2) physical therapy, 3)
acupuncture, 4) injection therapy, 5) had back surgery, 6) multidisciplinary pain
program, 7) psychological treatment for chronic pain such as cognitive behavioral
therapy or biofeedback, or 8) any other physician-prescribed treatment for chronic
low back pain.

Upon meeting, after obtaining written informed consent, the following inclusion criteria
are administered to determine protocol-eligibility:

1. Repeat PHQ-9 with score

2. Current depression (major depression, partial remission of major depression, minor
depression, or dysthymia) diagnosed with the PRIMEMD

3. 20-item Numeric Rating Scale for low back pain

4. The Montreal Cognitive Assessment (MoCA). Eligibility requires score of at least 24

5. No history of alcohol/substance abuse or dependence for the past six months. If
subjects took more analgesics than prescribed for CLBP but there was no other
evidence of abuse, they will be included. Alcohol and substance abuse will be
assessed with the MINI-International Neuropsychiatric Interview.

Exclusion Criteria:

The following exclusion criteria will be assessed during telephone screening. If the
individual responds in the affirmative to any of these conditions, they will not be
eligible:

1. Wheelchair-bound as this level of disability does not represent most older adults
living with CLBP.

2. Diagnosed with fibromyalgia; there is evidence that individuals with fibromyalgia may
have a differential treatment response to SNRIs.

3. Involved in a lawsuit related to back pain and/or receiving workers compensation.

Subjects must also not meet any of the following exclusion criteria:

1. Current or past psychotic-spectrum disorder or current or past bipolar disorder. This
will be determined with the PRIME-MD and MINI-Neuropsychiatric interview.

2. Medically unstable, delirious, or terminally ill; or medical contraindication to use
of venlafaxine therapy, including hypersensitivity, history of venlafaxine-induced
SIADH, uncontrolled narrow angle glaucoma, AST or ALT > 1.5x upper limit of normal.

3. Acute low back pain "red flag" superimposed on chronic low back pain suggesting
medically emergent condition (e.g., vertebral fracture, infection, cauda equina
syndrome, disk herniation, cancer).