Initiating buprenorphine to treat opioid use disorder without prerequisite withdrawal: a systematic review.
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ABSTRACT: Background
Opioid withdrawal symptoms prior to buprenorphine initiation may be intolerable and as a result, alternative strategies have emerged. We aim to systematically review the efficacy and safety of buprenorphine initiation that aims to omit prerequisite withdrawal.Methods
We conducted a systematic literature search of MEDLINE and CENTRAL from 1996 through April 10, 2020, augmented with searches in Google Scholar and www.clinicaltrials.gov . A study was included if it was in patients with substance use disorder or chronic pain that were taking a full mu opioid agonist and transitioning to buprenorphine without preceding withdrawal, and reported withdrawal during initiation as an outcome. Two investigators independently screened citations and articles for inclusion, collected data using a standardized data collection tool, and assessed study risk of bias.Results
We included 15 case reports/series, reporting 24 unique cases, in our qualitative synthesis. No controlled studies were identified. Microdosing and bridging with a buprenorphine patch were the most common strategies reported. Transition to buprenorphine with complete cessation of opioid agonists was achieved in 87.5% (n = 21) of cases. Withdrawal during initiation occurred in 58.3% (n = 14) of cases, two of which were at least moderate in severity.Conclusion
Buprenorphine initiation strategies that omit prerequisite withdrawal have emerged. Low quality evidence from case reports suggests withdrawal during initiation is common but most often mild in severity. There is an unmet need for controlled studies to inform their efficacy and safety compared with traditional strategies, including outcomes during initiation and in the long-term.
SUBMITTER: Adams KK
PROVIDER: S-EPMC8186092 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTwo phase I studies assessed the pharmacokinetics of buprenorphine, its metabolite norbuprenorphine, and naloxone following administration of buprenorphine/naloxone sublingual tablets in Chinese participants.MethodsIn the first phase I, open-label, single ascending-dose (SAD) study, 82 opioid-naïve volunteers received a single buprenorphine/naloxone dose ranging from 2 mg/0.5 mg to 24 mg/6 mg while under naltrexone block. In a second phase I, open-label, multiple ascending-dose (MAD) study, 27 patients with opioid dependence in withdrawal received buprenorphine/naloxone doses of either 16 mg/4 mg or 24 mg/6 mg for 9 consecutive days. Serial blood samples were collected after a single dose (SAD study) and at steady-state (MAD study). Pharmacokinetic parameters were calculated using non-compartmental analysis. Safety assessments included adverse events monitoring and laboratory tests.ResultsThe pharmacokinetic profiles of buprenorphine and naloxone were consistent between single- and multiple-dose studies. Peak plasma concentrations (Cmax) were reached early for buprenorphine (0.75-1.0 h) and naloxone (0.5 h), supporting rapid absorption. In the SAD study, increases in plasma exposures to buprenorphine and naloxone were less than dose proportional, in line with previous observations in Western populations. Buprenorphine-to-naloxone ratios for Cmax and area under the curve (AUC) were constant over the dose range investigated and also consistent with Western populations data. Steady state was reached within 7 days of daily dosing, with slight accumulation over repeated doses. No serious adverse events were observed.ConclusionsThe present data suggest that buprenorphine/naloxone pharmacokinetic profiles in Chinese participants are consistent, overall, with those in Western populations, supporting no differences in dosing.Clinical trial registrationThe protocols were registered on the official website of the China Food and Drug Administration (CFDA): http://www.chinadrugtrials.org.cn/ ; Registration numbers CTR20132963 (RB-CN-10-0012), CTR20140153 (RB-CN-10-0015).
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Project description:ImportanceThe COVID-19 pandemic disrupted medical care, impacting prescribing of opioid analgesics and buprenorphine for opioid use disorder. Understanding these patterns can help address barriers to care.ObjectiveTo evaluate how prescribing of opioid analgesics and buprenorphine for opioid use disorder changed throughout the COVID-19 pandemic among both new and existing patients.Design, setting, and participantsIn this cross-sectional study, use of opioid analgesics and buprenorphine for opioid use disorder from March 18 to September 1, 2020, was projected using a national database of retail prescriptions from January 1, 2018, to March 3, 2020. Actual prescribing was compared with projected levels for all, existing, and new patients.ExposuresThe data include prescriptions to patients independent of insurance status or type and cover 90% of retail prescriptions, 70% of mail-order prescriptions, and 70% of nursing home prescriptions.Main outcomes and measuresPrescriptions for opioid analgesics and buprenorphine for opioid use disorder. Outcomes included total number of prescriptions, total morphine milligram equivalents, mean morphine milligram equivalents per prescription, mean dispensed units per prescription, and number of patients filling prescriptions.ResultsA total of 452 691 261 prescriptions for opioid analgesics and buprenorphine for opioid use disorder were analyzed for 90 420 353 patients (50 921 535 female patients [56%]; mean [SD] age, 49 [20] years). From March 18 to May 19, 2020, 1877 million total morphine milligram equivalents of opioid analgesics were prescribed weekly vs 1843 million projected, a ratio of 102% (95% prediction interval [PI], 94%-111%; P = .71). The weekly number of opioid-naive patients receiving opioids was 370 051 vs 564 929 projected, or 66% of projected (95% PI, 63%-68%; P < .001). Prescribing of buprenorphine was as projected for existing patients, while the number of new patients receiving buprenorphine weekly was 9865 vs 12 008 projected, or 82% (95% PI, 76%-88%; P < .001). From May 20 to September 1, 2020, opioid prescribing for new patients returned to 100% of projected (95% PI, 96%-104%; P = .95), while the number of new patients receiving buprenorphine weekly was 10 436 vs 11 613 projected, or 90% (95% PI, 83%-97%; P = .009).Conclusions and relevanceIn this cross-sectional study, existing patients receiving opioid analgesics and buprenorphine for opioid use disorder generally maintained access to these medications during the COVID-19 pandemic. Opioid prescriptions for opioid-naive patients decreased briefly and then rebounded, while initiation of buprenorphine remained at a low rate through August 2020. Reductions in treatment entry may be associated with increased overdose deaths.
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Project description:OBJECTIVE:This study examined buprenorphine prescription uptake and expenditure trends among privately insured adults from 2003 to 2015 to inform efforts to expand opioid use disorder treatment. METHODS:A study with a repeated cross-sectional design using MarketScan prescription claims data was conducted to describe trends in total and new buprenorphine use and median total, plan, and out-of-pocket expenditures for a 30-day buprenorphine prescription among privately insured adults from 2003 to 2015. RESULTS:New and total buprenorphine users increased dramatically from 2003 to 2013 and plateaued. Total buprenorphine spending was stable from 2003 to 2008, increased from 2009 to 2013, and declined from 2013 to 2015. Out-of-pocket expenditures steadily decreased from $67 in 2003 to $32 in 2015 for a 30-day prescription. CONCLUSIONS:Buprenorphine treatment costs were stable for health plans and declined for privately insured adults since 2003. Identifying remaining barriers to addressing the opioid addiction treatment gap is a priority.
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Project description:ObjectiveAlthough opioid maintenance is a first-line approach for treating opioid use disorder (OUD), suboptimal treatment outcomes have been reported among emerging adults (EAs; 18-25 years of age). In this secondary analysis, we compared treatment outcomes between EAs and older adults (OAs; ? 26 years of age) receiving low-barrier, technology-assisted Interim Buprenorphine Treatment (IBT) during waitlist delays to comprehensive opioid maintenance treatment.MethodParticipants were 35 individuals with OUD who received IBT consisting of 12-weeks of buprenorphine maintenance with bi-monthly clinic visits and technology-assisted monitoring. At monthly follow-up assessments, participants completed staff-observed urinalysis, the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), and Addiction Severity Index (ASI).ResultsAt study intake, EAs (n = 10) reported greater past-year intravenous drug use and greater employment, legal, and psychiatric severity (p's < .05) compared to OAs (n = 25). Despite these initial differences, there were no significant differences in the percentages of urine specimens testing negative for illicit opioids between EA and OA participants at Study Week 4 (90 % vs. 88 %, p = .99), Week 8 (80 % vs. 76 %, p = .99) or Week 12 (60 % vs. 68 %, p = .71). Relative to their older peers, EAs also demonstrated significantly greater improvements on the BAI, BDI-II, and ASI Employment and Legal subscales (p's < .05).ConclusionsDespite presenting with greater past-year intravenous drug use and psychosocial severity relative to OAs, EAs responded favorably to the IBT intervention.
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Project description:ImportanceThe demand for medications for opioid use disorder (MOUD) in rural US counties far outweighs their availability. Novel approaches to extend treatment capacity include telemedicine (TM) and mobile treatment on demand; however, their combined use has not been reported or evaluated.ObjectiveTo evaluate the use of a TM mobile treatment unit (TM-MTU) to improve access to MOUD for individuals living in an underserved rural area.Design, setting, and participantsThis quality improvement study evaluated data collected from adult outpatients with a diagnosis of OUD enrolled in the TM-MTU initiative from February 2019 (program inception) to June 2020. Program staff traveled to rural areas in a modified recreational vehicle equipped with medical, videoconferencing, and data collection devices. Patients were virtually connected with physicians based more than 70 miles (112 km) away. Data analysis was performed from June to October 2020.InterventionPatients received buprenorphine prescriptions after initial teleconsultation and follow-up visits from a study physician specialized in addiction psychiatry and medicine.Main outcomes and measuresThe primary outcome was 3-month treatment retention, and the secondary outcome was opioid-positive urine screens. Exploratory outcomes included use of other drugs and patients' travel distance to treatment.ResultsA total of 118 patients were enrolled in treatment, of whom 94 were seen for follow-up treatment predominantly (at least 2 of 3 visits [>50%]) on the TM-MTU; only those 94 patients' data are considered in all analyses. The mean (SD) age of patients was 36.53 (9.78) years, 59 (62.77%) were men, 71 (75.53%) identified as White, and 90 (95.74%) were of non-Hispanic ethnicity. Fifty-five patients (58.51%) were retained in treatment by 3 months (90 days) after baseline. Opioid use was reduced by 32.84% at 3 months, compared with baseline, and was negatively associated with treatment duration (F = 12.69; P = .001). In addition, compared with the nearest brick-and-mortar treatment location, TM-MTU treatment was a mean of 6.52 miles (range, 0.10-58.70 miles) (10.43 km; range, 0.16-93.92 km) and a mean of 10 minutes (range, 1-49 minutes) closer for patients.Conclusions and relevanceThese data demonstrate the feasibility of combining TM with mobile treatment, with outcomes (retention and opioid use) similar to those obtained from office-based TM MOUD programs. By implementing a traveling virtual platform, this clinical paradigm not only helps fill the void of rural MOUD practitioners but also facilitates access to underserved populations who are less likely to reach traditional medical settings, with critical relevance in the context of the COVID-19 pandemic.
| S-EPMC8397932 | biostudies-literature