Background: The buprenorphine transdermal system (BTDS) is approved in the US for the management of chronic pain. Due to its high affinity for mu-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing mu-opioid-receptor agonists, including immediate-release (IR) opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable. Materials and methods: This post hoc analysis evaluated the use of IR opioids as supplemental analgesia during the management of moderate-severe chronic pain with BTDS at 52 US sites (BUP3015S, NCT01125917). Patients were categorized into IR-opioid and no-IR-opioid groups. At each visit of the extension phase, adverse events, concomitant medications, and information from the Brief Pain Inventory (BPI) were recorded. Results: The most common supplemental IR opioids prescribed during BTDS treatment (n=354) were hydrocodone-acetaminophen and oxycodone-acetaminophen. The mean daily dose of IR opioids (morphine equivalents) for supplemental analgesia was 22 mg. At baseline, BPI pain intensity and BPI - interference scores were higher for patients in the IR-opioid group. In both treatment groups, scores improved by week 4, and then were maintained throughout 6 months of the open-label extension trial. The incidence of treatment-emergent adverse events was similar in both groups. Conclusion: Patients who were prescribed IR opioids reported lower scores for BPI pain intensity and pain interference to levels similar to patients receiving BTDS without IR opioids, without increasing the rate or severity of treatment-emergent adverse events. Patients prescribed concomitant use of IR opioids with BTDS had greater treatment persistence. The results of this post hoc analysis provide support for the concomitant use of IR opioids for supplemental analgesia during the management of moderate-severe chronic pain with BTDS.

Background: Despite the many harms and limited efficacy of opioids in managing chronic noncancer pain (CNCP), they are commonly prescribed for these patients in North America. One of the harms associated with prolonged opioid use is opioid use disorder (OUD); however, the risk of addiction is uncertain. We systematically reviewed observational studies to establish the prevalence of (OUD), and to explore factors associated with OUD in patients with CNCP. Methods: We searched MEDLINE, EMBASE, CINAHL, Cochrane Library, and PsycINFO from inception to December 2018 to identify studies that explored the prevalence of OUD or risk factors for OUD in patients with CNCP. Two specialists in addiction medicine reviewed each potentially eligible study, blinded to results, to ensure their outcome met DSM-5 criteria for OUD. We pooled estimates of OUD across eligible studies using random-effects models. When possible, we pooled estimates of association with OUD for all independent variables reported by more than one study. Results: Twenty-two studies reported the prevalence of OUD, and six studies reported the association of 36 factors with OUD in patients with CNCP. The pooled prevalence of OUD was 20% (95% CI: 15% to 25%); however, we found evidence for small study effects (interaction p<0.001). When restricted to larger studies (≥900 patients), the pooled prevalence of OUD was 5.8% (95% CI: 2.8% to 9.5%; moderate certainty evidence). The prevalence of OUD was not associated with level of certainty of OUD criteria, under- or overestimation of instruments compared to DSM-5 criteria, severity of OUD, or risk of bias (interaction p values ranged from 0.34 to 0.92). Moderate certainty evidence demonstrated an association between OUD and male sex (OR 1.50 [95% CI: 1.05 to 2.14]; absolute risk increase (ARI) 2.7% [95% CI: 0.3% more to 5.8% more]), current smokers (OR 1.63; [95% CI: 1.25 to 2.12]; ARI 3.3% [1.3% more to 5.7% more]), and a history of mental health disorders (OR 1.49 [95% CI: 1.17 to 1.89]; ARI 2.6% [95% CI: 0.9% more to 4.6% more]). Low certainty evidence demonstrated an association between OUD and younger age (OR for every 10-year decrement, 1.60 [95% CI: 1.11 to 2.30]; ARI, 3.2% for every 10-year decrement [95% CI: 0.6% more to 6.6% more]). Moderate certainty evidence suggested no association between OUD and a history of alcohol abuse/dependence (OR 1.32 [95% CI: 0.84 to 2.07]; ARI 1.7% [95% CI: 0.9% less to 5.5% more]), and low certainty evidence suggested no association between OUD and a history of drug abuse (OR 1.51 [95% CI: 0.75 to 3.02]; ARI 2.7% [95% CI: 1.4% less to 9.9% more]). Conclusion: Moderate certainty evidence suggests that 6% of CNCP patients prescribed opioids will develop OUD. Younger men who smoke, with a history of mental health disorders, are at higher risk. Additional research is needed to establish the association between OUD and a history of drug or alcohol abuse. / Thesis / Master of Science (MSc) / Opioids are commonly prescribed for patients with chronic pain that is not due to cancer; however, long-term opioid use inevitably leads to physical dependence and may result in addiction. Prior studies have reported extremely variable rates of opioid use disorder (OUD) following prescription for chronic noncancer pain, ranging from less than 1% to more than 50%, which has led to considerable confusion. My systematic review found moderate certainty evidence that the prevalence of OUD following prescription for chronic pain is 5.8% (95% CI: 2.8% to 9.5%). Patients who were younger, current smokers, males, and had a history of mental health disorders, had a higher risk of developing OUD. These findings will help support shared care decision-making between patients with chronic pain considering opioid therapy and their healthcare providers.