Dataset Information

Opioid-induced analgesia among persons with opioid use disorder receiving methadone or buprenorphine: A systematic review of experimental pain studies.

ABSTRACT:

Background

Treating acute pain among persons with opioid use disorder (OUD) on opioid agonist therapy (OAT) is complex, and the therapeutic benefits of opioids remain unclear when weighted against their abuse potential and respiratory depressant effects.

Methods

We conducted a systematic review of experimental pain studies examining opioid-induced analgesia among persons with OUD on OAT. We searched multiple databases from inception to July 30, 2021. Study quality was assessed by previously established validity measures.

Results

Nine studies were identified, with a total of 225 participants, of whom 63% were male, and 37% were female. Six studies included methadone-maintained persons with OUD; four studies included buprenorphine-maintained persons with OUD; and three studies included healthy persons as comparison groups. Either additional doses of OAT or other opioids - morphine, oxycodone, hydromorphone, or remifentanil - were administered. In seven studies, persons with OUD on OAT did not experience analgesia, despite receiving opioid doses up to 20 times greater than those clinically used to treat severe pain among the opioid naïve. Conversely, in two studies, high-potency opioids did produce analgesia, albeit with greater abuse potential. Notably, persons with OUD on OAT remained vulnerable to respiratory depression.

Conclusions

Although persons with OUD on OAT can derive analgesic effects from opioids, high-potency compounds may be required to achieve clinically significant pain relief. Further, persons with OUD on OAT may remain vulnerable to opioid-induced abuse potential and respiratory depression. Together, these finding have clinical, methodological, and mechanistic implications for the treatment of acute pain in the context of OAT.

SUBMITTER: De Aquino JP

PROVIDER: S-EPMC8595687 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Opioid-induced analgesia among persons with opioid use disorder receiving methadone or buprenorphine: A systematic review of experimental pain studies.

De Aquino Joao P JP Parida Suprit S Avila-Quintero Victor J VJ Flores Jose J Compton Peggy P Hickey Thomas T Gómez Oscar O Gómez Oscar O Sofuoglu Mehmet M

Drug and alcohol dependence 20210922

<h4>Background</h4>Treating acute pain among persons with opioid use disorder (OUD) on opioid agonist therapy (OAT) is complex, and the therapeutic benefits of opioids remain unclear when weighted against their abuse potential and respiratory depressant effects.<h4>Methods</h4>We conducted a systematic review of experimental pain studies examining opioid-induced analgesia among persons with OUD on OAT. We searched multiple databases from inception to July 30, 2021. Study quality was assessed by ...[more]

PMID: 34601272

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Project description:BackgroundOpioid agonist therapy is strongly recommended for pregnant persons with opioid use disorder. Buprenorphine may be associated with more favorable neonatal and maternal outcomes than methadone, but existing data are limited.MethodsWe conducted a cohort study involving pregnant persons who were enrolled in public insurance programs in the United States during the period from 2000 through 2018 in which we examined outcomes among those who received buprenorphine as compared with those who received methadone. Exposure to the two medications was assessed in early pregnancy (through gestational week 19), late pregnancy (gestational week 20 through the day before delivery), and the 30 days before delivery. Risk ratios for neonatal and maternal outcomes were adjusted for confounders with the use of propensity-score overlap weights.ResultsThe data source for the study consisted of 2,548,372 pregnancies that ended in live births. In early pregnancy, 10,704 pregnant persons were exposed to buprenorphine and 4387 to methadone. In late pregnancy, 11,272 were exposed to buprenorphine and 5056 to methadone (9976 and 4597, respectively, in the 30 days before delivery). Neonatal abstinence syndrome occurred in 52.0% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73; 95% confidence interval [CI], 0.71 to 0.75). Preterm birth occurred in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (adjusted relative risk, 0.58; 95% CI, 0.53 to 0.62); small size for gestational age in 12.1% and 15.3%, respectively (adjusted relative risk, 0.72; 95% CI, 0.66 to 0.80); and low birth weight in 8.3% and 14.9% (adjusted relative risk, 0.56; 95% CI, 0.50 to 0.63). Delivery by cesarean section occurred in 33.6% of pregnant persons exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (adjusted relative risk, 1.02; 95% CI, 0.97 to 1.08), and severe maternal complications developed in 3.3% and 3.5%, respectively (adjusted relative risk, 0.91; 95% CI, 0.74 to 1.13). Results of exposure in late pregnancy were consistent with results of exposure in early pregnancy.ConclusionsThe use of buprenorphine in pregnancy was associated with a lower risk of adverse neonatal outcomes than methadone use; however, the risk of adverse maternal outcomes was similar among persons who received buprenorphine and those who received methadone. (Funded by the National Institute on Drug Abuse.).

Project description:BackgroundThe postpartum year is a vulnerable period for women with opioid use disorder, with increased rates of fatal and nonfatal overdose; however, data on the continuation of medications for opioid use disorder on a population level are limited.ObjectiveThis study aimed to examine the effect of discontinuing methadone and buprenorphine in women with opioid use disorder in the year following delivery and determine the extent to which maternal and infant characteristics are associated with time to discontinuation of medications for opioid use disorder.Study designThis population-based retrospective cohort study used linked administrative data of 211,096 deliveries in Massachusetts between 2011 and 2014 to examine the adherence to medications for opioid use disorder. Individuals receiving medications for opioid use disorder after delivery were included in the study. Here, demographic, psychosocial, prenatal, and delivery characteristics are described. Kaplan-Meier survival analysis and Cox regression modeling were used to examine factors associated with medication discontinuation.ResultsA total of 2314 women who received medications for opioid use disorder at delivery were included in our study. Overall, 1484 women (64.1%) continued receiving medications for opioid use disorder for a full 12 months following delivery. The rate of continued medication use varied from 34% if women started on medications for opioid use disorder the month before delivery to 80% if the medications were used throughout pregnancy. Kaplan-Meier survival curves differed by maternal race and ethnicity (the 12-month continuation probability was .65 for White non-Hispanic women and .51 for non-White women; P<.001) and duration of use of prenatal medications for opioid use disorder (12-month continuation probability was .78 for women with full prenatal engagement and .60 and .44 for those receiving medications for opioid use disorder ≥5 months [but not throughout pregnancy] and ≤4 months prenatally, respectively; P<.001). In all multivariable models, duration of receipt of prenatal medications for opioid use disorder (≤4 months vs throughout pregnancy: adjusted hazard ratio, 3.26; 95% confidence interval, 2.72-3.91) and incarceration (incarceration during pregnancy or after delivery vs none: adjusted hazard ratio, 1.79; 95% confidence interval, 1.52-2.12) were most strongly associated with the discontinuation of medications for opioid use disorder.ConclusionAlmost two-thirds of women with opioid use disorder continued using medications for opioid use disorder for a full year after delivery; however, the rates of medication continuation varied significantly by race and ethnicity, degree of use of prenatal medications for opioid use disorder, and incarceration status. Prioritizing medication continuation across the perinatal continuum, enhancing sex-specific and family-friendly recovery supports, and expanding access to medications for opioid use disorder despite being incarcerated can help improve postpartum medication adherence.

Project description:ImportanceStimulant medication use is common among individuals receiving buprenorphine for opioid use disorder (OUD). Associations between prescription stimulant use and treatment outcomes in this population have been understudied.ObjectivesTo investigate whether use of prescription stimulants was associated with (1) drug-related poisoning and (2) buprenorphine treatment retention.Design, setting, and participantsThis retrospective, recurrent-event cohort study with a case-crossover design used a secondary analysis of administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Primary analyses were conducted from March 1 through August 31, 2021. Individuals aged 12 to 64 years with an OUD diagnosis and prescribed buprenorphine who experienced at least 1 drug-related poisoning were included in the analysis. Unit of observation was the person-day.ExposuresDays of active stimulant prescriptions.Main outcomes and measuresPrimary outcomes were drug-related poisoning and buprenorphine treatment retention. Drug-related poisonings were defined using International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes; treatment retention was defined by continuous treatment claims until a 45-day gap was observed.ResultsThere were 13 778 567 person-days of observation time among 22 946 individuals (mean [SD] age, 32.8 [11.8] years; 50.3% men) who experienced a drug-related poisoning. Stimulant treatment days were associated with 19% increased odds of drug-related poisoning (odds ratio [OR], 1.19 [95% CI, 1.06-1.34]) compared with nontreatment days; buprenorphine treatment days were associated with 38% decreased odds of poisoning (OR, 0.62 [95% CI, 0.59-0.65]). There were no significant interaction effects between use of stimulants and buprenorphine. Stimulant treatment days were associated with decreased odds of attrition from buprenorphine treatment (OR, 0.64 [95% CI, 0.59-0.70]), indicating that stimulants were associated with 36% longer mean exposure to buprenorphine and its concomitant protection.Conclusions and relevanceAmong persons with OUD, use of prescription stimulants was associated with a modest increase in per-day risk of drug-related poisoning, but this risk was offset by the association between stimulant use and improved retention to buprenorphine treatment, which is associated with protection against overdose.

Project description:ImportanceIn 2017, the US Food and Drug Administration (FDA) approved a monthly injectable form of buprenorphine, extended-release buprenorphine; published data show that extended-release buprenorphine is effective compared with no treatment, but its current cost is higher and current retention is lower than that of transmucosal buprenorphine. Preliminary research suggests that extended-release buprenorphine may be an important addition to treatment options, but the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine remains unclear.ObjectiveTo evaluate the cost-effectiveness of extended-release buprenorphine compared with transmucosal buprenorphine.Design, setting, and participantsThis economic evaluation used a state transition model starting in 2019 to simulate the lifetime of a closed cohort of individuals with OUD presenting for evaluation for opioid agonist treatment with buprenorphine. The data sources used to estimate model parameters included cohort studies, clinical trials, and administrative data. The model relied on pharmaceutical costs from the Federal Supply Schedule and health care utilization costs from published studies. Data were analyzed from September 2021 to January 2023.InterventionsNo treatment, treatment with transmucosal buprenorphine, or treatment with extended-release buprenorphine.Main outcomes and measuresMean lifetime costs per person, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).ResultsThe simulated cohort included 100 000 patients with OUD receiving (61% male; mean [SD] age, 38 [11] years) or not receiving medication treatment (58% male, mean [SD] age, 48 [18] years). Compared with no medication treatment, treatment with transmucosal buprenorphine yielded an ICER of $19 740 per QALY. Compared with treatment with transmucosal buprenorphine, treatment with extended-release buprenorphine yielded lower effectiveness by 0.03 QALYs per person at higher cost, suggesting that treatment with extended-release buprenorphine was dominated and not preferred. In probabilistic sensitivity analyses, treatment with transmucosal buprenorphine was the preferred strategy 60% of the time. Treatment with extended-release buprenorphine was cost-effective compared with treatment with transmucosal buprenorphine at a $100 000 per QALY willingness-to-pay threshold only after substantial changes in key parameters.Conclusions and relevanceIn this economic evaluation of extended-release buprenorphine compared with transmucosal buprenorphine for the treatment of OUD, extended-release buprenorphine was not associated with efficient allocation of limited resources when transmucosal buprenorphine was available. Future initiatives should aim to improve retention rates or decrease costs associated with extended-release buprenorphine.

Project description:ImportanceOpioid-stimulant co-use is a common problem with few evidence-based treatments.ObjectiveTo examine bupropion slow release (SR) enhancement of a tailored abstinence incentive program for stimulant use in persons with opioid use disorder.Design, setting, and participantsThis 26-week, double-blind, placebo-controlled randomized clinical trial with a 4-week follow-up period was conducted at 4 methadone treatment programs in Baltimore, Maryland. Included participants were persons receiving methadone for the treatment of opioid use disorder with past 3-month cocaine use and current cocaine use disorder between March 2015 and September 2019. Data were analyzed from November 2020 through August 2022.InterventionsA 6-week incentive induction period with monetary incentives for evidence of cocaine abstinence during thrice-weekly urine testing was conducted. Persons achieving 2 weeks of consecutive abstinence during induction were assigned to the relapse prevention group (20 individuals); otherwise, individuals were assigned to the abstinence initiation group (60 individuals). Participants were randomized within incentive groups to bupropion SR (150 mg oral twice daily; 40 participants) or placebo (40 participants). Incentives were available until week 26, and study medication ended week 30.Main outcomes and measuresThe mean percentage of participants with cocaine abstinence (by negative urinalysis or self-report) during weeks 7 to 26 (ie, the incentive intervention period) and 27 to 30 (ie, the follow-up period) and the percentage of participants testing negative for cocaine at weeks 26 and 30 were assessed. Main effects of medication collapsed across incentive conditions and sensitivity analyses of medications within incentive conditions were assessed. Analyses were conducted in the modified intention-to-treat sample (ie, 80 individuals who received ≥1 dose of study medication) and completers (ie, 52 individuals who completed ≥1 visit during week 30).ResultsAmong 80 participants (42 Black [52.5% ] and 35 White [43.8%]; mean [SD] age, 45.7 (9.4) years; 52 males [65.0%]) receiving methadone for opioid use disorder, 40 participants were randomized to receive bupropion SR and 40 participants to receive placebo. No significant difference on urinalysis or self-reported cocaine use was observed between medication groups. Sensitivity analyses revealed differential patterns for incentive subgroups. Participants in the relapse prevention group had high abstinence (>80%; eg, during weeks 7-26 in the modified intention-to-treat analysis, 410 of 456 samples [89.9%] from participants in the bupropion SR group tested negative for cocaine) throughout the trial regardless of whether they were randomized to bupropion SR or placebo. Participants in the abstinence initiation group had better outcomes with bupropion SR than placebo throughout the trial (mean [SD] total number of samples testing negative for cocaine, 30.3 [21.6] samples for bupropion SR vs 17.1 [14.9] samples for placebo; P = .05) and more participants receiving bupropion SR than placebo were abstinent at the end of the study (20 of 30 participants [66.7%] vs 9 of 30 participants [30.0%]; P = .04).Conclusions and relevanceIn this randomized clinical trial, an overall benefit for bupropion SR vs placebo when combined with a financial abstinence incentive program was not observed. Results among incentive subgroups suggest that continued evaluation of medications, including bupropion SR, for stimulant treatment using a tailored approach that factors early abstinence into study design and interpretation may be needed.Trial registrationClinicalTrials.gov Identifier: NCT02111798.

Project description:ObjectiveTo estimate whether methadone, buprenorphine, or detoxification treatment is the most cost-effective approach to the management of opioid use disorder (OUD) during pregnancy.MethodsWe created a decision analytic model that compared the cost effectiveness (eg, the marginal cost of the strategy in U.S. dollars divided by the marginal effectiveness of the strategy, measured in quality-adjusted life-years [QALYs]) of initiation of methadone, buprenorphine, or detoxification in treatment of OUD during pregnancy. Probabilities, costs, and utilities were estimated from the existing literature. Incremental cost-effective ratios for each strategy were calculated, and a ratio of $100,000 per QALY was used to define cost effectiveness. One-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed.ResultsUnder base assumptions, initiation of buprenorphine was more effective at a lower cost than either methadone or detoxification and thus was the dominant strategy. Buprenorphine was no longer cost effective if the cost of methadone was 8% less than the base-case estimate ($1,646/month) or if the overall costs of detoxification were 121% less than the base-case estimate for the detoxification cost multiplier, which was used to increase the values of both inpatient and outpatient management of detoxification by a factor of 2. Monte Carlo analyses revealed that buprenorphine was the cost-effective strategy in 70.5% of the simulations. Direct comparison of buprenorphine with methadone demonstrated that buprenorphine was below the incremental cost-effective ratio in 95.1% of simulations; direct comparison between buprenorphine and detoxification demonstrated that buprenorphine was below the incremental cost-effective ratio in 45% of simulations.ConclusionUnder most circumstances, we estimate that buprenorphine is the cost-effective strategy when compared with either methadone or detoxification as treatment for OUD during pregnancy. Nonetheless, the fact that buprenorphine was not the cost-effective strategy in almost one out of three of simulations suggests that the robustness of our model may be limited and that further evaluation of the cost-effective approach to the management of OUD during pregnancy is needed.

Dataset Information

Opioid-induced analgesia among persons with opioid use disorder receiving methadone or buprenorphine: A systematic review of experimental pain studies.

Background

Methods

Results

Conclusions

Publications

Opioid-induced analgesia among persons with opioid use disorder receiving methadone or buprenorphine: A systematic review of experimental pain studies.

Similar Datasets

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