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A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder.

ABSTRACT: As the opioid epidemic continues to grow across the United States, the number of patients requiring treatment for opioid use disorder continues to climb. Although medication-assisted treatment presents a highly effective tool that can help address this epidemic, its use has been limited. Nonetheless, with easier dosing protocols (compared to the more complex dosing required of methadone due to its long and variable half-life) and fewer prescribing limitations (may be prescribed outside the setting of federally approved clinics), the increase in buprenorphine use in the United States has been dramatic in recent years. Despite buprenorphine's demonstrated efficacy, patient-specific factors can alter the response to the medications, which may lead to treatment failure in some patients. Clinical characteristics (sex, concurrent medications, and mental health comorbidities) as well as social determinants of health (housing status, involvement with the criminal justice system, and socioeconomic status) may impact treatment outcomes. Furthermore, a growing body of data suggests that genetic variations can alter pharmacological effects and influence therapeutic response. This review will cover the available pharmacogenomic data for the use of buprenorphine in the management of opioid use disorders. Pharmacogenomic determinants that affect opioid receptors, the dopaminergic system, metabolism of buprenorphine, and adverse events are discussed. Although much of the existing data comes from observational studies, clinical research is ongoing. Nevertheless, the development of pharmacogenomic-guided strategies has the potential to reduce opioid misuse, improve clinical outcomes, and save healthcare resources.

SUBMITTER: Segui HA

PROVIDER: S-EPMC7709797 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder.

Seguí Hemanuel Arroyo HA Melin Kyle K Quiñones Darlene Santiago DS Duconge Jorge J

Journal of translational genetics and genomics 20200730

As the opioid epidemic continues to grow across the United States, the number of patients requiring treatment for opioid use disorder continues to climb. Although medication-assisted treatment presents a highly effective tool that can help address this epidemic, its use has been limited. Nonetheless, with easier dosing protocols (compared to the more complex dosing required of methadone due to its long and variable half-life) and fewer prescribing limitations (may be prescribed outside the setti ...[more]

PMID: 33274315

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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.

Project description:OBJECTIVE:Although buprenorphine treatment reduces risk of overdose and death in opioid use disorder, most patients discontinue treatment within a few weeks or months. Adverse health outcomes following buprenorphine discontinuation were compared among patients who were successfully retained beyond 6 months of continuous treatment, a minimum treatment duration recently endorsed by the National Quality Forum. METHODS:A retrospective longitudinal cohort analysis was performed using the MarketScan multistate Medicaid claims database (2013-2017), covering 12 million beneficiaries annually. The sample included adults (18-64 years of age) who received buprenorphine continuously for ?180 days by cohorts retained for 6-9 months, 9-12 months, 12-15 months, and 15-18 months. For outcome assessment in the postdiscontinuation period, patients had to be continuously enrolled in Medicaid for 6 months after buprenorphine discontinuation. Primary adverse outcomes included all-cause emergency department visits, all-cause inpatient hospitalizations, opioid prescriptions, and drug overdose (opioid or non-opioid). RESULTS:Adverse events were common across all cohorts, and almost half of patients (42.1%-49.9%) were seen in the emergency department at least once. Compared with patients retained on buprenorphine for 6-9 months (N=4,126), those retained for 15-18 months (N=931) had significantly lower odds of emergency department visits (odds ratio=0.75, 95% CI=0.65-0.86), inpatient hospitalizations (odds ratio=0.79, 95% CI=0.64-0.99), and filling opioid prescriptions (odds ratio=0.67, 95% CI=0.56-0.80) in the 6 months following discontinuation. Approximately 5% of patients across all cohorts experienced one or more medically treated overdoses. CONCLUSIONS:Risk of acute care service use and overdose were high following buprenorphine discontinuation irrespective of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high.

Project description:ImportanceEmergency departments (EDs) sporadically use a high-dose buprenorphine induction strategy for the treatment of opioid use disorder (OUD) in response to the increasing potency of the illicit opioid drug supply and commonly encountered delays in access to follow-up care.ObjectiveTo examine the safety and tolerability of high-dose (>12 mg) buprenorphine induction for patients with OUD presenting to an ED.Design, setting, and participantsIn this case series of ED encounters, data were manually abstracted from electronic health records for all ED patients with OUD treated with buprenorphine at a single, urban, safety-net hospital in Oakland, California, for the calendar year 2018. Data analysis was performed from April 2020 to March 2021.InterventionsED physicians and advanced practice practitioners were trained on a high-dose sublingual buprenorphine induction protocol, which was then clinically implemented.Main outcomes and measuresVital signs; use of supplemental oxygen; the presence of precipitated withdrawal, sedation, and respiratory depression; adverse events; length of stay; and hospitalization during and 24 hours after the ED visit were reported according to total sublingual buprenorphine dose (range, 2 to >28 mg).ResultsAmong a total of 391 unique patients (median [interquartile range] age, 36 [29-48] years), representing 579 encounters, 267 (68.3%) were male and 170 were (43.5%) Black. Homelessness (88 patients [22.5%]) and psychiatric disorders (161 patients [41.2%]) were common. A high dose of sublingual buprenorphine (>12 mg) was administered by 54 unique clinicians during 366 (63.2%) encounters, including 138 doses (23.8%) greater than or equal to 28 mg. No cases of respiratory depression or sedation were reported. All 5 (0.8%) cases of precipitated withdrawal had no association with dose; 4 cases occurred after doses of 8 mg of buprenorphine. Three serious adverse events unrelated to buprenorphine were identified. Nausea or vomiting was rare (2%-6% of cases). The median (interquartile range) length of stay was 2.4 (1.6-3.75) hours.Conclusions and relevanceThese findings suggest that high-dose buprenorphine induction, adopted by multiple clinicians in a single-site urban ED, was safe and well tolerated in patients with untreated OUD. Further prospective investigations conducted in multiple sites would enhance these findings.

Project description:ObjectiveThe authors examined the impact of COVID-19-related policies reducing barriers to telehealth delivery of buprenorphine treatment for opioid use disorder (OUD) on buprenorphine treatment across different modalities (telephone, video, and in-person visits).MethodsThis was a national retrospective cohort study with interrupted time-series analyses to examine the impact of policy changes in March 2020 on buprenorphine treatment for OUD in the Veterans Health Administration, during the year before the start of the COVID-19 pandemic (March 2019 to February 2020) and during the first year of the pandemic (March 2020 to February 2021). The authors also examined trends in the use of telephone, video, and in-person visits for buprenorphine treatment and compared patient demographic characteristics and retention in buprenorphine treatment across the two periods.ResultsThe number of patients receiving buprenorphine increased from 13,415 in March 2019 to 15,339 in February 2021. By February 2021, telephone visits were used by the most patients (50.2%; 4,456 visits), followed by video visits (32.4%; 2,870 visits) and in-person visits (17.4%; 1,544 visits). During the pre-pandemic period, the number of patients receiving buprenorphine increased significantly by 103 patients per month. After the COVID-19 policy changes, there was an immediate increase of 265 patients in the first month, and the number continued to increase significantly, at a rate of 47 patients per month. The demographic characteristics of patients receiving buprenorphine during the pandemic period were similar to those during the pre-pandemic period, but the proportion of patients reaching 90-day retention on buprenorphine treatment decreased significantly from 49.6% to 47.7%, while days on buprenorphine increased significantly from 203.8 to 208.7.ConclusionsThe number of patients receiving buprenorphine continued to increase after the COVID-19 policy changes, but the delivery of care shifted to telehealth visits, suggesting that any reversal of COVID-19 policies must be carefully considered.

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A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder.

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A review of the pharmacogenomics of buprenorphine for the treatment of opioid use disorder.

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