Buprenorphine and Methadone for Opioid-dependent Chronic Back Pain Patients
Condition: Low Back Pain
MeSH terms: Back Pain; Low Back Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic pain patients are treated with prescription opioids and many exhibit opioid
      addiction. Currently, there are no evidence-based guidelines to better manage patients with
      chronic pain and coexistent opioid addiction. This study compares 6-months buprenorphine and
      methadone treatment in these patients. The investigators hypothesize that both buprenorphine
      and methadone treatment will reduce pain and addiction behaviors and increase functioning in
      these patients.
    

Detailed description: 
      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.
    

Intervention name(s): Methadone; Buprenorphine/naloxone
Intervention type(s): Drug; Drug
Intervention description(s): 10-60 mg/day divided by 2-4 times a day for 6 months; 4-16 mg/day divided by 2-4 times a day for 6 months
Other intervention name(s): Dolophine; Suboxone
Intervention MeSH terms: Buprenorphine; Methadone; Buprenorphine, Naloxone Drug Combination; Naloxone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chronic pain; opioid dependence; methadone; buprenorphine; substance use disorder