Prescription Opioid Abuse Among Pain Patients: Predictors of Relapse

All participants will be admitted to the GCRU, the SRU, or the CRR and maintained on
sublingual Bup/Ntx. During the first week after admission, participants will be withdrawn
from their prior opioid analgesic regimen and will be stabilized on one of three doses of
buprenorphine/naloxone (2/0.5, 8/2, or 16/4 mg per day). Participants will be treated for
emergent withdrawal symptoms with supplemental supplemental medications (clonidine,
clonazepam, compazine, ketorolac tromethamine, hydroxyzine, ranitidine, ondansetron,
zolpidem) until withdrawal symptoms have dissipated, based on self-report and observer
ratings. Each buprenorphine dose will be administered in equal divided doses according to a
QID dosing schedule, and each dose will be maintained for a two-week period (one week of
stabilization followed by one week of laboratory testing). Thus, stabilization will occur
during Weeks 1, 3, and 5; testing will occur in Weeks 2, 4, and 6. Participants may receive
an unaccompanied pass of up to 72 hours during Weeks 3 and 5 to attend to family obligations.
Participants will be informed that urine toxicology screens will be conducted upon their
return to the hospital, and that testing positive for drugs other than the study medication
may result in discharge from the study. The order of administration of these three doses will
vary among subjects in a randomized manner. At the completion of laboratory testing in Week
6, participants will be stabilized on 16 mg of buprenorphine. This final week of
stabilization ensures that (1) any acute effects of high-dose oxycodone administration in the
laboratory have dissipated and do not affect opioid dependence level; and (2) participants
have sufficient opportunity to stabilize on the dose of buprenorphine on which they will be
maintained during the outpatient phase.

Participants whose pain is not adequately relieved by Suboxone (buprenorphine/naloxone) will
we removed from the study by the investigators. A criterion for dropout during the inpatient
phase will be: clear decline in functional status, such as sustained worsening of mobility or
marked decline in level of activity. In the event that average daily pain level worsens from
baseline by 30% or more (e.g. 6/10 to 9/10), a clinical evaluation will be performed to
consider whether the participant should be removed from the protocol, or should be allowed to
continue to participate. The clinical determination will include an assessment of whether
pain has improved throughout the inpatient stay as a range of doses are tested.

During the subsequent outpatient phase medication will be dispensed on a weekly basis and
will consist of (1) a standing maintenance dose of 16 mg Suboxone (buprenorphine/naloxone),
and (2) doses of Suboxone to be taken on a prn basis for breakthrough pain (prn doses will
not exceed 25% of the total daily standing dose). Patients will report to the Substance Use
Research Center (SURC) twice per week for 12 weeks for clinical visits.

Inclusion Criteria:

1. DSM-IV criteria for opioid abuse and prescription opioid physical dependence

2. 18-65 years of age

3. Stable weight (<10% change in 3 months) and stable physical health

4. Chronic pain syndrome (e.g., osteoarthritic pain or chronic lower back pain
with/without history of surgery) of moderate (4-7) average daily pain of 6+ months
duration; opioid medication maintenance for 6+ months

5. Seeking treatment for chronic pain

6. Must be expected to achieve a good analgesic effect from buprenorphine

Exclusion Criteria:

1. DSM-IV untreated Axis I disorders (e.g. MDD, BAD, psychotic disorders, eating
disorders) requiring treatment

2. Regular consumption of more than 500 mg caffeine daily

3. Primary pain diagnosis of neuropathic pain, malignant pain, or headache

4. History of allergy, adverse reaction, or sensitivity to opioids, including
buprenorphine

5. Pregnancy, lactation, or history of having given birth or had abortion or miscarriage
within the last six months, or unwillingness to use an effective method of birth
control (e.g. condoms, birth control pills, abstinence)

6. Psychotropic medications which would potentially interfere with study procedures

7. Inability to read or understand the self-report assessment forms unaided

8. Use of medications known to interfere with buprenorphine metabolism, such as
disulfiram, neuroleptics, azole antifungals (e.g. ketoconazole), macrolide antibiotics
(e.g. erythromycin), and HIV protease inhibitors (e.g. ritonavir, indivair, and
saquinavir)

9. Methadone-dependent

10. Current heroin dependence

11. Current buprenorphine maintenance

12. History of failed treatment with buprenorphine maintenance for pain

13. Acute hepatitis with elevated liver function tests (i.e. AST and ALT > 3 times the
upper limit of normal) or impaired renal function (creatinine > 1.2 )

14. Any medical condition that might interfere with the study or significantly increase
the medical risks of study participation

15. Participant is currently receiving any investigational drug or has used any
investigational drug within 30 days of study entry

16. History of significant cardiovascular disease, such as coronary artery disease or
hypertension requiring more than two anti-hypertensive agents

17. History of insulin-dependent diabetes

18. Body mass index of <18.5 or > 35.0