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Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals.

ABSTRACT: BACKGROUND:Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16?mg sublingual buprenorphine/naloxone. METHODS:Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16?mg of hydromorphone or 4, 4, 8, and 16?mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events. RESULTS:A significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32?mg of IV hydromorphone (means ± SD) (10?±?14?s, P = 0.035) and 32?mg of buprenorphine (3?±?5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16?mg (18?±?24?s, P = 0.018) and 32?mg (48?±?73?s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16?mg (1?±?15?s, P = 0.619) or 32?mg (7?±?16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting. CONCLUSIONS:In this acute clinical pain model, high doses of IV hydromorphone (16 to 32?mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.

SUBMITTER: Huhn AS

PROVIDER: S-EPMC6295244 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals.

Huhn Andrew S AS Strain Eric C EC Bigelow George E GE Smith Michael T MT Edwards Robert R RR Tompkins D Andrew DA

Anesthesiology 20190101 1

<h4>Background</h4>Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone.<h4>Methods</h4>Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controll ...[more]

PMID: 30418214

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Project description:Importance:Buprenorphine is an efficacious, widely used treatment for opioid use disorder (OUD). Daily oral transmucosal formulations can be associated with misuse, diversion, and nonadherence; these limitations may be obviated by a sustained release formulation. Objective:To evaluate the ability of a novel, weekly, subcutaneous buprenorphine depot formulation, CAM2038, to block euphorigenic opioid effects and suppress opioid withdrawal in non-treatment-seeking individuals with OUD. Design, Setting, and Participants:This multisite, double-blind, randomized within-patient study was conducted at 3 controlled inpatient research facilities. It involved 47 adults with DSM-V moderate-to-severe OUD. The study was conducted from October 12, 2015 (first patient enrolled), to April 21, 2016 (last patient visit). Interventions:A total of five 3-day test sessions evaluated the response to hydromorphone (0, 6, and 18 mg intramuscular in random order; 1 dose/session/day). After the first 3-day session (ie, qualification phase), participants were randomized to either CAM2038 weekly at 24 mg (n?=?22) or 32 mg (n?=?25); the assigned CAM2038 dose was given twice, 1 week apart (day 0 and 7). Four sets of sessions were conducted after randomization (days 1-3, 4-6, 8-10, and 11-13). Main Outcomes and Measures:The primary end point was maximum rating on the visual analog scale for drug liking. Secondary end points included other visual analog scale (eg, high and desire to use), opioid withdrawal scales, and physiological and pharmacokinetic outcomes. Results:A total of 46 of 47 randomized participants (mean [SD] age, 35.5 [9] years; 76% male [n?=?35]) completed the study. Both weekly CAM2038 doses produced immediate and sustained blockade of hydromorphone effects (liking maximum effect, CAM2038, 24 mg: effect size, 0.813; P?<?.001, and CAM2038, 32 mg: effect size, 0.753; P?<?.001) and suppression of withdrawal (Clinical Opiate Withdrawal Scale, CAM2038, 24 mg: effect size, 0.617; P?<?.001, and CAM2038, 32 mg: effect size, 0.751; P?<?.001). CAM2038 produces a rapid initial rise of buprenorphine in plasma with maximum concentration around 24 hours, with an apparent half-life of 4 to 5 days and approximately 50% accumulation of trough concentration from first to second dose (trough concentration?=?0.822 and 1.23 ng/mL for weeks 1 and 2, respectively, with 24 mg; trough concentration?=?0.993 and 1.47 ng/mL for weeks 1 and 2, respectively, with 32 mg). Conclusions and Relevance:CAM2038 weekly, 24 and 32 mg, was safely tolerated and produced immediate and sustained opioid blockade and withdrawal suppression. The results support the use of this depot formulation for treatment initiation and stabilization of patients with OUD, with the further benefit of obviating the risk for misuse and diversion of daily buprenorphine while retaining its therapeutic benefits. Trial Registration:Clinicaltrials.gov Identifier: NCT02611752.

Project description:BACKGROUND:Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). METHODS:Intravenous heroin users (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions. RESULTS:Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of 'drug liking' and 'desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. CONCLUSIONS:These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Dataset Information

Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals.

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Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals.

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