Methadone, Buprenorphine, Oxycodone, Fentanyl and Tramadol in Multiple Postmortem Matrices.
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ABSTRACT:
SUBMITTER: Havig SM
PROVIDER: S-EPMC9282245 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
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Methadone, Buprenorphine, Oxycodone, Fentanyl and Tramadol in Multiple Postmortem Matrices.
Havig Stine Marie SM Vindenes Vigdis V Øiestad Åse Marit Leere ÅML Rogde Sidsel S Thaulow Cecilie Hasselø CH
Journal of analytical toxicology 20220701 6
Peripheral blood (PB) concentrations are generally preferred for postmortem toxicological interpretation, but some autopsy cases may lack blood for sampling due to decomposition or large traumas, etc. In such cases, other tissues or bodily fluids must be sampled; however, limited information exists on postmortem concentrations in matrices other than blood. Pericardial fluid (PF), muscle and vitreous humor (VH) have been suggested as alternatives to blood, but only a few studies have investigated ...[more]
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Project description:ObjectiveOpioid overdose survivors present to emergency departments (EDs) and many EDs have developed programs to initiate buprenorphine. The impact of the increasing use of buprenorphine in ED and by other providers is unknown while opioid mortality continues to rise. Public mortality data do not distinguish buprenorphine from other prescription opioids. Our objective was to determine when changes in overdose mortality trends occurred comparing deaths involving buprenorphine to oxycodone, hydrocodone, and methadone.MethodsThis observational study utilized the drug-involved mortality database including US death certificates (2010‒2017) in which buprenorphine, oxycodone, hydrocodone, or methadone were contributing causes of death (determined through textual analysis). Population- and drug utilization-adjusted mortality rates were examined using disjointed linear regression. Buprenorphine-involved deaths were stratified by polysubstance involvement.ResultsThe population-adjusted mortality rates for buprenorphine-involved deaths were lowest compared to other opioids; however, the change in rate for buprenorphine increased faster than oxycodone, hydrocodone, and methadone at 8.9% each quarter-year (95% confidence interval [CI]: 8.0, 9.8) from 2010 to mid-2016 when it stabilized. After adjusting for changes in dispensing over the study period, buprenorphine-involved mortality rates were increasing at 5.3% (95% CI: 4.6, 6.1) each quarter-year. In 2017, 94% buprenorphine-involved deaths had at least one other drug contributing to the cause of death.ConclusionsGiven the low mortality, high proportions of polysubstance mortality, and the mixed agonist/antagonist mechanism of action, use of buprenorphine alone likely presents a lower risk for overdose than comparators. Mortality rose faster than dispensing, signaling need to ensure people understand buprenorphine risks, particularly polysubstance use, balanced against importance for treating opioid use disorders.
| S-EPMC11499299 | biostudies-literature
Project description:BackgroundMethadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy.MethodsWe conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference.ResultsTreatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events.ConclusionsThese results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).
| S-EPMC3073631 | biostudies-literature
Project description:AimTo determine the effects of in utero exposure to methadone or buprenorphine on infant neurobehavior.DesignThree sites from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial participated in this substudy.SettingMedical Centers that provided comprehensive maternal care to opioid-dependent pregnant women in Baltimore, MD, Providence, RI and Vienna, Austria.ParticipantsThirty-nine full-term infants.MeasurementsThe Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS) was administered to a subgroup of infants on postpartum days 3, 5, 7, 10, 14-15 and 28-30.FindingsWhile neurobehavior improved for both medication conditions over time, infants exposed in utero to buprenorphine exhibited fewer stress-abstinence signs (P < 0.001), were less excitable (P < 0.001) and less over-aroused (P < 0.01), exhibited less hypertonia (P < 0.007), had better self-regulation (P < 0.04) and required less handling (P < 0.001) to maintain a quiet alert state relative to in utero methadone-exposed infants. Infants who were older when they began morphine treatment for withdrawal had higher self-regulation scores (P < 0.01), and demonstrated the least amount of excitability (P < 0.02) and hypertonia (P < 0.02) on average. Quality of movement was correlated negatively with peak NAS score (P < 0.01), number of days treated with morphine for NAS (P < 0.01) and total amount of morphine received (P < 0.03). Excitability scores were related positively to total morphine dose (P < 0.03).ConclusionWhile neurobehavior improves during the first month of postnatal life for in utero agonist medication-exposed neonates, buprenorphine exposure results in superior neurobehavioral scores and less severe withdrawal than does methadone exposure.
| S-EPMC4337995 | biostudies-literature
Project description:ImportanceBuprenorphine treatment of opioid use disorder (OUD) is safe and effective, but opioid withdrawal during treatment initiation is associated with poor retention in care. As fentanyl has replaced heroin in the drug supply, case reports and surveys have indicated increased concern for buprenorphine-precipitated withdrawal (PW); however, some observational studies have found a low incidence of PW.ObjectiveTo estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients.Design, setting, and participantsThis retrospective cohort study at 3 academic hospitals in Philadelphia, Pennsylvania, included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Exclusion criteria included low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine.ExposureBuprenorphine initiation with an initial dose of at least 2 mg of sublingual buprenorphine after a Clinical Opiate Withdrawal Scale (COWS) score of 8 or higher. Additional exposures included 4 predefined factors potentially associated with PW: severity of opioid withdrawal before buprenorphine (COWS score of 8-12 vs ≥13), initial buprenorphine dose (2 vs 4 or ≥8 mg), body mass index (BMI) (<25 vs 25 to <30 or ≥30; calculated as weight in kilograms divided by height in meters squared), and urine fentanyl concentration (0 to <20 vs 20 to <200 or ≥200 ng/mL).Main outcome and measuresThe main outcome was PW incidence, defined as a 5-point or greater increase in COWS score from immediately before to within 4 hours after buprenorphine initiation. Logistic regression was used to estimate the odds of PW associated with the 4 aforementioned predefined factors.ResultsThe cohort included 226 patients (150 [66.4%] male; mean [SD] age, 38.6 [10.8] years). Overall, 26 patients (11.5%) met criteria for PW. Among patients with PW, median change in COWS score was 9 points (IQR, 6-13 points). Of 123 patients with confirmed fentanyl use, 20 (16.3%) had PW. In unadjusted and adjusted models, BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW.Conclusions and relevanceIn this retrospective cohort study, 11.5% of patients developed PW after buprenorphine initiation in ED or hospital settings. Future studies should confirm the rate of PW and assess whether bioaccumulated fentanyl is a risk factor for PW.
| S-EPMC11437388 | biostudies-literature
Project description:BACKGROUNDPotent synthetic opioids, such as fentanyl, are increasingly abused, resulting in unprecedented numbers of fatalities from respiratory depression. Treatment with the high-affinity mu-opioid receptor partial agonist buprenorphine may prevent fatalities by reducing binding of potent opioids to the opioid receptor, limiting respiratory depression.METHODSTo characterize buprenorphine-fentanyl interaction at the level of the mu-opioid receptor in 2 populations (opioid-naive individuals and individuals who chronically use high-dose opioids), the effects of escalating i.v. fentanyl doses with range 0.075-0.35 mg/70 kg (opioid naive) and 0.25-0.70 mg/70 kg (chronic opioid use) on iso-hypercapnic ventilation at 2-3 background doses of buprenorphine (target plasma concentrations range: 0.2-5 ng/mL) were quantified using receptor association/dissociation models combined with biophase distribution models.RESULTSBuprenorphine produced mild respiratory depression, while high doses of fentanyl caused pronounced respiratory depression and apnea in both populations. When combined with fentanyl, buprenorphine produced a receptor binding-dependent reduction of fentanyl-induced respiratory depression in both populations. In individuals with chronic opioid use, at buprenorphine plasma concentrations of 2 ng/mL or higher, a protective effect against high-dose fentanyl was observed.CONCLUSIONOverall, the results indicate that when buprenorphine mu-opioid receptor occupancy is sufficiently high, fentanyl is unable to activate the mu-opioid receptor and consequently will not cause further respiratory depression in addition to the mild respiratory effects of buprenorphine.TRIAL REGISTRATIONTrialregister.nl, no. NL7028 (https://www.trialregister.nl/trial/7028)FUNDINGIndivior Inc., North Chesterfield, Virginia, USA.
| S-EPMC9090248 | biostudies-literature
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.).
| S-EPMC9873239 | biostudies-literature
Project description:Methadone and buprenorphine are both efficacious treatments for opioid dependency, but they also have different pharmacological properties and clinical delivery methods that can affect their acceptability to patients. This study was intended to increase our knowledge of heroin-dependent individuals' perceptions of methadone vs. buprenorphine maintenance based on actual experiences with each. The study sample consists of heroin-dependent men at the Rikers Island jail in New York City who were voluntarily randomly assigned to methadone or buprenorphine maintenance in jail. Methadone patients were more likely to report feeling uncomfortable the first few days, having side/withdrawal effects during treatment, and being concerned about continued dependency on medication after release. In contrast, buprenorphine patients' main issue was the bitter taste. All of the buprenorphine patients stated that they would recommend the medication to others, with almost all preferring it to methadone. Ninety-three percent of buprenorphine vs. 44% of methadone patients intended to enroll in those respective treatments after release, with an added one-quarter of the methadone patients intending to enroll in buprenorphine instead. These results reinforce the importance of increasing access to buprenorphine treatment in the community for indigent heroin-dependent offenders.
| S-EPMC3527632 | biostudies-literature
Project description:BackgroundMethadone and buprenorphine are recommended to treat opioid use disorders during pregnancy. However, the literature on the relationship between longer-term effects of prenatal exposure to these medications and childhood development is both spare and inconsistent.MethodsParticipants were 96 children and their mothers who participated in MOTHER, a randomized controlled trial of opioid-agonist pharmacotherapy during pregnancy. The present study examined child growth parameters, cognition, language abilities, sensory processing, and temperament from 0 to 36 months of the child's life. Maternal perceptions of parenting stress, home environment, and addiction severity were also examined.ResultsTests of mean differences between children prenatally exposed to methadone vs. buprenorphine over the three-year period yielded 2/37 significant findings for children. Similarly, tests of mean differences between children treated for NAS relative to those not treated for NAS yielded 1/37 significant finding. Changes over time occurred for 27/37 child outcomes including expected child increases in weight, head and height, and overall gains in cognitive development, language abilities, sensory processing, and temperament. For mothers, significant changes over time in parenting stress (9/17 scales) suggested increasing difficulties with their children, notably seen in increasing parenting stress, but also an increasingly enriched home environment (4/7 scales) CONCLUSIONS: Findings strongly suggest no deleterious effects of buprenorphine relative to methadone or of treatment for NAS severity relative to not-treated for NAS on growth, cognitive development, language abilities, sensory processing, and temperament. Moreover, findings suggest that prenatal opioid agonist exposure is not deleterious to normal physical and mental development.
| S-EPMC5906792 | biostudies-literature
Project description:AimTo determine pre- and post-dosing effects of prenatal methadone compared to buprenorphine on fetal wellbeing.DesignA secondary analysis of data derived from the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, a double-blind, double-dummy, randomized clinical trial.SettingSix United States sites and one European site that provided comprehensive opioid-dependence treatment to pregnant women.ParticipantsEighty-one of the 131 opioid-dependent pregnant women completing the MOTHER clinical trial, assessed between 31 and 33 weeks of gestation.MeasurementsTwo fetal assessments were conducted, once before and once after study medication dosing. Measures included mean fetal heart rate (FHR), number of FHR accelerations, FHR reactivity in the fetal non-stress test (NST) and biophysical profile (BPP) score.FindingsSignificant group differences were found for number of FHR accelerations, non-reactive NST and BPP scores (all Ps < 0.05). There were no significant group differences before time of dosing. Significant decreases (all Ps < 0.05) occurred from pre- to post-dose assessment for mean FHR, FHR accelerations, reactive NST and fetal movement. The decrease in accelerations and reactive NST were significant only for fetuses in the methadone group, and this resulted in a significantly lower likelihood of a reactive NST compared to fetuses in the buprenorphine group.ConclusionBuprenorphine compared with methadone appears to result in less suppression of mean fetal heart rate, fetal heart rate reactivity and the biophysical profile score after medication dosing and these findings provide support for the relative safety of buprenorphine when fetal indices are considered as part of the complete risk-benefit ratio.
| S-EPMC4277183 | biostudies-literature
Project description:ObjectivesBuprenorphine can precipitate withdrawal in opioid-dependent persons with recent fentanyl use. However, the prevalence of this phenomenon is not clinically established. We sought to evaluate the incidence of buprenorphine-precipitated withdrawal in persons who use fentanyl.MethodsWe collected self-report data on opioid withdrawal symptoms after buprenorphine use, and, as a comparator, after methadone use, in 1679 individuals seeking treatment for opioid use disorder across 49 addiction treatment centers in the United States.ResultsThe odds of developing severe withdrawal symptoms significantly increased when taking buprenorphine within 24 hours after fentanyl use (OR = 5.202, 95% CI = 1.979-13.675, P = 0.001), and within 24 to 48hours after fentanyl use (OR = 3.352, 95% CI =1.237-9.089, P = 0.017). As expected, patients did not report significantly higher rates of withdrawal when taking methadone after fentanyl use. Of those who waited less than 24hours after fentanyl before using buprenorphine or methadone, 22.19% (n = 152 of 685) and 11.56% (n = 23 of 199), respectively, reported severe opioid withdrawal.ConclusionsThis study supports previous anecdotal reports of buprenorphine-precipitated withdrawal from fentanyl. The odds of withdrawal symptoms significantly increased when taking buprenorphine after recent (within 48 hours) fentanyl use, however, this relationship was not observed in persons taking methadone, suggesting that this effect is specific to buprenorphine. Further research is urgently needed to describe the pharmacokinetics of non-medical fentanyl use to improve buprenorphine inductions strategies.
| S-EPMC9124721 | biostudies-literature