Association of Naloxone Coprescription Laws With Naloxone Prescription Dispensing in the United States

Importance: To mitigate the opioid overdose crisis, states have implemented a variety of legal interventions aimed at increasing access to the opioid antagonist naloxone. Recently, Virginia and Vermont mandated the coprescription of naloxone for potentially at-risk patients. Objective: To assess the association between naloxone coprescription legal mandates and naloxone dispensing in retail pharmacies. Design, Setting, and Participants: This was a population-based, state-level cohort study. The sample included all prescriptions dispensed for naloxone in the retail pharmacy setting contained in IQVIA\u27s national prescription audit, which represents 90% of all retail pharmacies in the United States. The unit of observation was state-month and the study period was January 1, 2011, to December 31, 2017. Exposures: State legal intervention mandating naloxone coprescription. Main Outcomes and Measures: Number of naloxone prescriptions dispensed. State rates of naloxone prescriptions dispensed per month per 100 000 standard population were calculated. Results: The rate of naloxone dispensing increased after implementation of legal mandates for naloxone coprescription. An estimated 88 naloxone prescriptions per 100 000 were dispensed in Virginia and 111 prescriptions per 100 000 were dispensed in Vermont during the first full month the legal requirement was effective. In comparison, 16 naloxone prescriptions per 100 000 were dispensed in the 10 states (including the District of Columbia) with the highest opioid overdose death rates and 6 prescriptions per 100 000 were dispensed in the 39 remaining states. The number of naloxone prescriptions dispensed was associated with the legal mandate for naloxone coprescription (incidence rate ratio [IRR], 7.75; 95% CI, 1.22-49.35). Implementation of the naloxone coprescription mandate was associated with an estimated 214 additional naloxone prescriptions dispensed per month in the period following the mandates, holding all other variables constant. Among covariates, naloxone access laws (IRR, 1.37; 1.05-1.78), opioid overdose death rates (IRR, 1.06; 95% CI, 1.04-1.08), the percentage of naloxone prescriptions paid by third-party payers (IRR 1.009; 1.008-1.010), and time (IRR, 1.06; 95% CI, 1.05-1.07) were significantly associated with naloxone prescription dispensing. Conclusions and Relevance: These study findings suggest that legally mandated naloxone prescription for those at risk for opioid overdose may be associated with substantial increases in naloxone dispensing and further reduction in opioid-related harm

Buprenorphine for Medication-Assisted Treatment of Opioid Use Disorder in Pregnancy: Relationship to Neonatal Opioid Withdrawal Syndrome

Objective To examine the relationship between antepartum buprenorphine dose for medication-assisted treatment (MAT) of opioid use disorder (OUD) and incident neonatal opioid withdrawal syndrome (NOWS). Study Design We performed a prospective cohort study of pregnant women with a singleton gestation diagnosed with OUD and receiving buprenorphine for MAT at a tertiary care academic institution from July 2015 to January 2017. We divided the study cohort into two groups—pregnancies with versus without NOWS. Substance abuse patterns in pregnancy, maternal, and neonatal clinical outcomes were compared. Results The incidence of NOWS was 31.11% (n = 28/90) in our study cohort. Pregnancies with NOWS had a significantly higher rate of benzodiazepine positive urine tests and number of positive urine drug screen (UDS) results for illicit opioids. The group without NOWS had significantly higher number of patients with an appropriate UDS result at delivery through postpartum. Rates of neonatal intensive care unit (NICU) admission, length of NICU stay, and maximum Finnegan score were significantly higher in the group with NOWS. Neither the initial (10.6 ± 5.2 versus 10.3 ± 4.8 mg, p = 0.80) nor the final buprenorphine doses (13.3 ± 5.1 versus 13.0 ± 4.6 mg, p = 0.81) were significantly different between study groups. Conclusion The occurrence of NOWS was not related to buprenorphine dose used for MAT

Buprenorphine Physician Supply: Relationship with State-Level Prescription Opioid Mortality

Background: Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation’s prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states. Methods: The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of prescription opioid overdose mortality in 2013 at or above the median (\u3e 5.5 deaths per 100,000 population) and those with rates below the median. State-level growth curves were estimated using mixed-effects regression to compare rates of growth between high and low overdose states. Results: The total supply and the supply of 100-patient buprenorphine physicians grew significantly (total supply from 7.7 to 9.9 per 100,000 population, p \u3c 0.001; 100-patient supply from 2.2 to 3.4 per 100,000 population, p \u3c 0.001). Rates of growth were significantly greater in high overdose states when compared to low overdose states (total supply b = 0.033, p \u3c 0.01; 100-patient b = 0.022, p \u3c 0.01). Conclusions: The magnitude of the US prescription opioid crisis, as measured by the rate of prescription opioid overdose mortality, is associated with growth in the number of buprenorphine physicians. Because this observational design cannot establish causality, further research is needed to elucidate the factors influencing physicians’ decisions to begin prescribing buprenorphine

Gabapentin Drug Misuse Signals: A Pharmacovigilance Assessment Using the FDA Adverse Event Reporting System

Background: Although there have been increasing reports of intentional gabapentin misuse, epidemiological evidence for the phenomenon is limited. The purpose of this study was to determine whether there are pharmacovigilance abuse signals for gabapentin.Methods: Using FDA Adverse Events Reporting System reports from January 1, 2005 to December 31, 2015, we calculated pharmacovigilance signal measures (i.e., reporting odds ratio, proportional reporting ratio, information component, and empirical Bayes geometric mean) for abuse-related adverse event (AR-AE)-gabapentin pairs. Loglinear modeling assessed the frequency of concurrent reporting of abuse-related and abusespecific AEs (AS-AEs) associated with gabapentin. Findings were compared to a positive (pregabalin) and negative (duloxetine) control.Results: From 2005-2015 there were 5,951,229 unique AE reports submitted to the FDA including 99,977 for gabapentin, 73,977 for duloxetine, and 97,813 for pregabalin. Significant drug-AR-AE pair signals involving gabapentin included: drug abuser, multiple drug overdose, and substance-induced psychotic disorder. Significant drug AR-AE signals involving gabapentin and pregabalin, but not duloxetine, were: ataxia, dependence, drug abuse, increased drug tolerance, and overdose. Compared to duloxetine, gabapentin had significantly greater odds of a coreport for an AS-AE with drug withdrawal syndrome (OR: 6.55), auditory hallucinations (OR: 4.57), delusions (OR: 2.36), euphoric mood (OR: 5.45), ataxia (OR: 2.85), drug abuser (OR: 3.01), aggression (OR: L98), psychotic disorder (OR: 1.96), and feeling abnormal (OR: 1.31).Conclusions: We identified abuse-related signals for gabapentin and highlighted several CNS effects that may be associated with its abuse. Gabapentin prescribers should be aware of the drug\u27s abuse liability and effects that may accompany its use

Oral Cannabidiol Does Not Produce a Signal for Abuse Liability in Frequent Marijuana Smokers

Background—Cannabidiol (CBD) is a naturally occurring constituent of the marijuana plant. In the past few years, there has been great interest in the therapeutic effects of isolated CBD and it is currently being explored for numerous disease conditions (e.g., pain, epilepsy, cancer, various drug dependencies). However, CBD remains a Schedule I drug on the U.S. Controlled Substances Act (CSA). Despite its status, there are no well-controlled data available regarding its abuse liability. Methods—Healthy, frequent marijuana users (n=31) were enrolled in this within subject, randomized, placebo-controlled, double-blind, multisite study that administered oral cannabidiol (0, 200, 400, 800 mg) alone and in combination with smoked marijuana (0.01%, 5.3-5.8% THC). Participants received one dose combination across 8 once-weekly outpatient sessions (7.5 hrs). The primary findings on the drug interaction effects were previously reported (Haney et al., 2016). The present study is a secondary analysis of the data to examine the abuse liability profile of oral cannabidiol (200, 400, 800 mg) in comparison to oral placebo and active smoked marijuana (5.3-5.8% THC). Results—Active marijuana reliably produced abuse-related subjective effects (e.g., high) (p \u3c .05). However, CBD was placebo-like on all measures collected (p \u3e .05). Conclusions—Overall, CBD did not display any signals of abuse liability at the doses tested and these data may help inform U.S. regulatory decisions regarding CBD schedule on the CSA

Adaptation of a Standard Extended-Release Naltrexone (XR-NTX) Protocol for Rural Re-Entering Offenders with OUD

BACKGROUND: Despite a growing body of empirical support for the effectiveness of extended-release naltrexone (XR-NTX) to reduce opioid relapse among people with opioid use disorder (OUD) transitioning from a correctional facility to the community, continuity of care following release remains challenging. This paper describes a research-based adaptation of a state\u27s standard of care XR-NTX protocol using the ADAPT-ITT framework for delivery in a non-traditional, non-treatment, community criminal justice setting (P&P office), as well as the expansion of services by a local Federally Qualified Health Center (FQHC) provider who would, for the first time, be going to the jail and P&P office to provide XR-NTX and related treatment. METHOD: The present study focuses on the first seven phases (Assessment through Training) of the ADAPT-ITT framework in the adaptation of the Department of Corrections (DOC) protocol in preparation for a pilot trial for induction in a rural jail and during the transition to a rural community. Expert clinical review and focus groups with key stakeholders in criminal justice supervision and the local providers in the FQHC informed the needed adaptations to the existing XR-NTX protocol for initiation at the jail and ongoing administrations in the community. RESULTS: Findings from stakeholder focus groups, study team review, topical expert review, and a theater test suggested that there were critical adaptations needed in both content and context at the patient and clinic level. CONCLUSION: Health and justice officials should consider the need to tailor and adapt evidence-based approaches for real-world locations that high-risk, justice-involved individuals visit in order to reduce barriers and increase access to critically needed treatment for OUD

A Qualitative Analysis of Gabapentin Misuse and Diversion Among People Who Use Drugs in Appalachian Kentucky

Gabapentin, an anticonvulsant and analgesic for postherpetic neuralgia, has been thought to have no abuse potential despite numerous published reports to the contrary. Gabapentin has been linked with impaired driving and opioid use, highlighting the need to more fully understand its risk profile. Thirty-three individuals reporting recent nonmedical use of gabapentin were recruited from two ongoing longitudinal studies of drug users in Appalachian Kentucky to participate in focus groups. Four sessions were held (two in the community and two in jail settings), during which participants responded to questions regarding their personal experiences with gabapentin misuse. Focus group participants were similar to other gabapentin users in the larger cohort studies with respect to demographics and drug use behaviors. Overall, the sample reported having initiated gabapentin more than 10 years earlier after having it prescribed for a legitimate, though generally off-label, medical indication (e.g., pain, anxiety, opioid detoxification). Participants reported use of gabapentin in combination with buprenorphine, other opioids, cocaine, and caffeine to produce sought-after central nervous system effects (e.g., muscle relaxation, pain reduction, sleep induction, feeling drunk, and feeling “high”). Focus group responses highlighted the low cost of gabapentin for the purpose of getting high and noted increasing popularity in the community, particularly over the last 2 years. Gabapentin was a prominent drug of abuse in two cohorts of the primarily opioid-using individuals. Providers should be aware of gabapentin’s abuse potential, and a reexamination of the need for scheduling is warranted

Behavioral and Enhanced Perinatal Intervention (B-EPIC): A Randomized Trial Targeting Tobacco Use among Opioid Dependent Pregnant Women

Background Opioid use during pregnancy is a significant public health issue. The standard of care for treating opioid use disorder during pregnancy includes medications for opioid disorder (MOUD). However, tobacco use often goes unaddressed among pregnant women on MOUD. In 2018, our team received a National Institute on Drug Abuse (NIDA) funded R34 to conduct a three year-randomized trial to test the feasibility of a novel tobacco intervention for pregnant women receiving MOUD. Aims The aims of this study are: (1) to determine the impact of the B-EPIC intervention on maternal tobacco use and stage of change; (2) to determine the impact of B-EPIC on tobacco-related maternal and infant health outcomes including gestational age at birth, birthweight, NAS diagnosis and severity, and number of ear and respiratory infections during the first six months; (3) to compare healthcare utilization and costs incurred by pregnant patients that receive the B-EPIC intervention versus TAU. Methods We plan to enroll 100 pregnant women on MOUD for this randomized controlled trial (B-EPIC intervention n = 50 and treatment as usual n = 50). A major strength of this study is its wide range of health and economic outcomes assessed on mother, neonate and the infant. Conclusions Despite the very high rates of smoking among pregnant women with OUD, there are few tobacco treatment interventions that have been tailored for this high - risk population. The overall goal of this study is to move towards a tobacco treatment standard for pregnant women receiving treatment for OUD

Patterns of Buprenorphine Initiation Treatment for Opioid Use Disorder and Association with Opioid-related Overdose Deaths

Oral presentation at the 38th International Society for Pharmacoepidemiolog