Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder.

BACKGROUND: BUP-XR (SUBLOCADE®) is the first buprenorphine extended-release subcutaneous injection approved in the USA for monthly treatment of moderate-to-severe opioid use disorder (OUD). Among patients with OUD, those who inject or use high doses of opioids likely require higher doses of buprenorphine to maximize treatment efficacy. The objective of this analysis was to compare the efficacy and safety of 100-mg versus 300-mg maintenance doses of BUP-XR in OUD patients who inject opioids. METHODS: This was a secondary analysis of a randomized, double-blind, placebo-controlled study in which adults with moderate or severe OUD received monthly injections of BUP-XR (2 × 300-mg doses, then 4 × 100-mg or 300-mg maintenance doses) or placebo for 24 weeks. Abstinence was defined as opioid-negative urine drug screens combined with negative self-reports collected weekly. Each participant's percentage abstinence was calculated after the first, second, and third maintenance doses in opioid-injecting and non-injecting participants. The proportion of participants achieving opioid abstinence in each group was also calculated weekly. Treatment retention rate following the first maintenance dose was estimated for opioid-injecting participants with Kaplan-Meier method. Risk-adjusted comparisons were made via inverse propensity weighting using propensity scores. Buprenorphine plasma concentration-time profiles were compared between injecting and non-injecting participants. The percentages of participants reporting treatment-emergent adverse events were compared between maintenance dose groups within injecting and non-injecting participants separately. RESULTS: BUP-XR 100-mg and 300-mg maintenance doses were equally effective in non-injecting participants. However, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements over the 100-mg maintenance dose for treatment retention and opioid abstinence. Exposure-response analyses confirmed that injecting participants would require higher buprenorphine plasma concentrations compared to non-injecting opioid participants to achieve similar efficacy in terms of opioid abstinence. Importantly, both 100- and 300-mg maintenance doses had comparable safety profiles, including hepatic safety events. CONCLUSIONS: These analyses show clear benefits of the 300-mg maintenance dose in injecting participants, while no additional benefit was observed in non-injecting participants relative to the 100-mg maintenance dose. This is an important finding as opioid-injecting participants represent a high-risk and difficult-to-treat population. Optimal buprenorphine dosing in this population might facilitate harm reduction by improving abstinence and treatment retention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02357901.

Massage Impact on Pain in Opioid-dependent Patients in Substance Use Treatment.

BACKGROUND: Chronic pain is a common cause of health care utilization and high levels of pain are pronounced in individuals engaged in methadone maintenance treatment. Although massage has been demonstrated to alleviate chronic pain symptoms, its use as an adjunctive therapy to modify pain during opioid-replacement treatment is absent from the literature. PURPOSE: To consider the efficacy of Swedish massage in reducing pain in opioid-dependent patients with chronic pain receiving methadone treatment. SETTING: Trial was conducted at a nonprofit methadone treatment center serving low-income patients. RESEARCH DESIGN: A randomized clinical trial with randomized to either 1) massage plus treatment-as-usual (TAU) (n = 27) or 2) TAU (n = 24). Durability of treatment effect was evaluated at Week 12. INTERVENTION: Eight weekly 50-minute Swedish massage sessions plus TAU or TAU alone. MAIN OUTCOME MEASURES: Pain, anxiety, depression, physical functioning, decreased substance use, and improvement in treatment engagement. RESULTS: Randomized participants were comparable at Baseline for demographic, pain, physical, and emotional variables. Massage group reported improved pain scores; worst pain had a clinically significant 2-point improvement while the other pain scores did not. Overall improvements were not observed in treatment engagement or levels of anxiety, depression, or physical functioning. A subgroup of the participants, who felt they could be pain-free, consistently reported improvements in pain from Baseline to Week 8, and this was most pronounced and clinically significant in the massage group. CONCLUSIONS: These preliminary findings do not support an overall clinically significant positive effect of Swedish massage on reduction in pain ratings or improvement in anxiety, depression, or treatment engagement in a substance-using, opioid-dependent population with chronic pain. Future nonpharmacologic pain research in marginalized substance-using populations may wish to consider some of the challenges and limitations faced in this project.

Pain and emotional distress among substance-use patients beginning treatment relative to a representative comparison group.

OBJECTIVES: A secondary analysis assessed health-related quality-of-life (HRQOL) characteristics (ie, anxiety, depression, fatigue, and types of pain) among patients entering substance-use treatment and identified characteristics specific to treatment modalities relative to a representative comparison group. METHODS: As part of a larger alcohol bank assessment, substance-use patients (n = 406) beginning methadone treatment (n = 170) or other outpatient treatment (n = 236) and a comparison group representative of the general population (n = 1000) completed a survey measuring anxiety, depression, fatigue, pain interference, and pain in the last 7 days. Previous studies lacked comparable and concurrent assessments across these 3 groups. RESULTS: Patients entering substance-use treatment had relatively high levels of emotional distress and poorer HRQOL relative to the general population. Among treatment modalities, patients beginning methadone treatment reported the highest levels of pain interference and pain behavior and the poorest physical functioning. Before the potentially modifying effects of methadone maintenance, patients beginning agonist therapy reported the greatest levels of compromised quality of life. CONCLUSIONS: These data present the magnitude of differences in HRQOL characteristics between treatment and comparison groups using the same assessment rubric and may help inform the design and timing of treatment modalities, thereby enhancing treatment efficacy for patients.