Buprenorphine and Methadone for Opioid-dependent Chronic Back Pain Patients

Chronic non-malignant pain (i.e. pain unrelated to cancer that persists beyond the usual
course of disease or injury) is a major concern in the United States. Opioids are the most
commonly prescribed medication to treat patients with chronic non-malignant pain. However,
in one systematic review of chronic low back pain, the authors note that, although clinical
trials suggest that opioids are effective for short-term use (≤ 16 weeks), the effectiveness
of long-term opioids (> 16 weeks) for pain relief and improved physical functioning is less
clear.

Five to 31 percent of chronic back pain patients prescribed long-term opioids show aberrant
drug-taking behaviors. Many develop tolerance and withdrawal, 43% of these patients exhibit
opioid addiction. Therefore, patients with chronic pain and a co-occurring opioid addiction
present a clinical challenge. In such cases, referral to addiction experts is recommended,
but specialized treatment is currently based on expert opinion and observational studies.

The expert recommendation is detoxification followed by treatment with methadone,
buprenorphine, naltrexone, or non-opioid analgesics in conjunction with behavioral
counseling. Discontinuing short-acting opioid medications increases pain and will make it
difficult for these patients to abstain from opioids due to the severity of pain. However,
continuing these opioid medications worsens their addiction and renders opioids ineffective
in the treatment of pain. Research is needed to compare the various medication-assisted
treatments.

Long-acting opioids (e.g., methadone, buprenorphine) are used to replace treatment with
short-acting opioids (e.g., hydrocodone, oxycodone). Methadone is a full mu-opioid-receptor
agonist that can be effective in treating pain. Two small studies suggest that treatment of
patients with chronic pain and co-occurring substance use disorder with methadone and
adjunctive pain management therapy is superior to non-opioid treatment protocols. Despite
the demonstration that methadone can be effective as both an analgesic and for opioid
addiction treatment, it possesses side effects (e.g, constipation) and serious adverse
events (e.g, respiratory depression, risk of overdose) that limit its use, making physicians
reluctant to prescribe methadone.

Buprenorphine, a partial opioid agonist, is an alternative to methadone for treatment of
opioid addiction, has a safety profile superior to methadone, and possesses analgesic
properties. For outpatient use, buprenorphine is combined with naloxone (BUP/NLX) to reduce
the potential for abuse (i.e., IV administration). When given to those who abuse
prescription opioids BUP/NLX possesses better treatment outcomes than those who abuse
heroin. In one uncontrolled case series of 95 participants, Malinoff and his colleagues
concluded that the effectiveness in the treatment of opioid dependence, in providing
analgesia, and the low abuse liability make BUP/NLX a potentially useful treatment for
patients with chronic pain and co-occurring opioid addiction. In a randomized controlled
trial by Blondell et al. (2010), treatment with BUP/NLX was superior to the
abstinence-oriented approach in regards to treatment retention in patients with chronic pain
and co-existent opioid addiction. However, there has not been a randomized clinical trial
comparing BUP/NLX with methadone maintenance in chronic pain patients with opioid addiction.
Preliminary data suggest that both 6-months BUP/NLX and methadone treatment results
analgesia, but methadone treatment results in better addiction outcomes. The present study
is designed to determine the complexity of recovery outcomes (e.g., functioning, mental
health) in chronic pain patients. Clinicians need evidence-based guidelines to more
effectively manage patients who have both chronic pain and evidence of opioid misuse or
addiction behaviors.

In this study, we plan to investigate whether patients treated with BUP/NLX and usual care
will have improved clinical outcomes as those provided with methadone treatment and usual
care. Specifically, we propose to give 63 patients BUP/NLX therapy for 6 months
(experimental group) and 63 patients methadone therapy over 6 (active comparator). We
hypothesize that patients given BUP/NLX treatment will have similar outcomes as those
receiving methadone maintenance with respect to functioning, mental health, pain level, and
treatment retention.

Inclusion Criteria:

1. have a well-documented chronic pain disorder due to past back surgery,

2. have a chronic back pain syndrome,

3. have evidence of opioid addiction,

4. prior attempt at abstinence-oriented treatment documented by the referring physician,

5. be able to understand spoken and written English,

6. reside in Erie or Niagara counties,

7. have health insurance or other ability to pay for treatment with the approval from
patient's primary physician;

8. have no prior history of methadone or BUP/NLX maintenance treatment since the last
surgery,

9. not be a member of a vulnerable population, including prisoners

Exclusion Criteria:

1. homeless, or any patient without a "locator" (no means to participate in the
follow-up data collection interviews by phone),

2. inability to give consent,

3. those with major co-occurring psychiatric disorders,

4. EKG showing prolonged QT and/or previous cardiac issues,

5. are taking a medication that is contraindicated with methadone,

6. medically unstable,

7. urine positive for cocaine at initial visit,

8. pregnant women