Pronounced Regional Variation in Esketamine and Ketamine Prescribing to US Medicaid Patients.

Ketamine and esketamine are efficacious for treatment-resistant depression. Unlike other antidepressants, ketamine lacks a therapeutic delay and decreases the risk for suicide. This cross-sectional study geographically characterized ketamine and esketamine prescribing to United States (US) Medicaid patients. Ketamine and esketamine prescription rates and spending per state were obtained. Between 2009 and 2020, ketamine prescribing rates peaked in 2013 followed by a general decline. For ketamine and esketamine in 2019, Montana (967/million enrollees) and Indiana (425) showed significantly higher prescription rates, respectively, relative to the national average. A total of 21 states prescribed neither ketamine nor esketamine in 2019. There was a 121.3% increase in esketamine prescriptions from 2019 to 2020. North Dakota (1,423) and North Carolina (1,094) were significantly elevated relative to the average state for esketamine in 2020. Ten states prescribed neither ketamine nor esketamine in 2020. Medicaid programs in 2020 spent 72.7-fold more for esketamine ($25.3 million) than on ketamine (0.3 million). Despite the effectiveness of ketamine and esketamine for treatment-resistant depression and anti-suicidal properties, their use among Medicaid patients was limited and highly variable in many areas of the US. Further research to better understand the origins of this state-level variation is needed.

Pronounced State-Level Disparities in Medicaid Prescribing of Buprenorphine for Opioid Use Disorder (2019-2020).

OBJECTIVE: The purpose of this study was to analyze buprenorphine prescribing across states in Medicaid patients during 2019-2020. METHOD: Buprenorphine prescriptions per Medicaid enrollee per state were calculated for 2019 and 2020. Data analysis was conducted with buprenorphine formulations that are approved by the U.S. Food & Drug Administration for opioid use disorder (OUD; including generic and brand name formulations of buprenorphine mono product and buprenorphine/naloxone combination products) using Microsoft Excel. The totals of mono product buprenorphine were divided over the total of combination buprenorphine/naloxone in 2019 and 2020 to obtain the ratio of mono/combo. Formulations of buprenorphine indicated for pain were excluded. States outside 95% confidence intervals (1.96 standard deviations above and below the mean) were considered statistically significant. RESULTS: The overall change in buprenorphine prescribing between 2019 and 2020 was modest (+3.6%) but highly variable, with more than a 10% increase in 17 states (Iowa = +100.5%, p < .05) but more than a 10% decrease in 9 states (Alabama = -68.5%, p < .05). Total amount reimbursed in 2019 increased (+9.9%) to $1.42 billion in 2020. Branded formulations accounted for two fifths (39.5%) of prescribing but more than two thirds (66.8%) of spending in 2020. CONCLUSIONS: The COVID-19 pandemic exacerbated state-level disparities in buprenorphine prescribing for OUD among Medicaid patients. Legislation expanding buprenorphine-waivered providers and Medicaid expansion may have contributed to the statistically significant changes in state buprenorphine prescriptions.

Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic.

OBJECTIVES: Opioid use disorder (OUD) is a major public health concern in the USA, resulting in high rates of overdose and other negative outcomes. Methadone, an OUD treatment, has been shown to be effective in reducing the risk of overdose and improving overall health and quality of life. This study analysed the distribution of methadone for the treatment of OUD across the USA over the past decade and through the COVID-19 pandemic. DESIGN: Retrospective observational study using secondary data analysis of the Drug Enforcement Administration and Medicaid Databases. SETTING: USA. PARTICIPANTS: Patients who were dispensed methadone at US opioid treatment programmes (OTPs). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the overall pattern in methadone distribution and the number of OTPs in the USA per year. The secondary outcome was Medicaid prescriptions for methadone. RESULTS: Methadone distribution for OUD has expanded significantly over the past decade, with an average state increase of +96.96% from 2010 to 2020. There was a significant increase in overall distribution of methadone to OTP from 2010 to 2020 (+61.00%, p<0.001) and from 2015 to 2020 (+26.22%, p<0.001). However, the distribution to OTPs did not significantly change from 2019 to 2021 (-5.15%, p=0.491). There was considerable state-level variation in methadone prescribing to Medicaid patients with four states having no prescriptions. CONCLUSIONS: There have been dynamic changes in methadone distribution for OUD. Furthermore, pronounced variation in methadone distribution among states was observed, with some states having no OTPs or Medicaid coverage. New policies are urgently needed to increase access to methadone treatment, address the opioid epidemic in the USA and reduce overdose deaths.

An analysis of patterns of distribution of buprenorphine in the United States using ARCOS, Medicaid, and Medicare databases.

Opioid overdose remains a problem in the United States despite pharmacotherapies, such as buprenorphine, in the treatment of opioid use disorder. This study characterized changes in buprenorphine use. Using the Drug Enforcement Administration's ARCOS, Medicaid, and Medicare claims databases, patterns in buprenorphine usage in the United States from 2018 to 2020 were analyzed by examining percentage changes in total grams distributed and changes in grams per 100 K people in year-to-year usage based on ZIP code and state levels. For ARCOS from 2018 to 2019 and 2019 to 2020, total buprenorphine distribution in grams increased by 16.2% and 12.6%, respectively. South Dakota showed the largest statewide percentage increase in both 2018-2019 (66.1%) and 2019-2020 (36.7%). From 2018 to 2019, the ZIP codes ND-577 (156.4%) and VA-222 (-82.1%) had the largest and smallest percentage changes, respectively. From 2019 to 2020, CA-932 (250.2%) and IL-603 (-36.8%) were the largest and smallest, respectively. In both 2018-2019 and 2019-2020, PA-191 had the second highest increase in grams per 100K while OH-452 was the only ZIP code to remain in the top three largest decreases in grams per 100K in both periods. Among Medicaid patients in 2018, there was a nearly 2000-fold difference in prescriptions per 100k Medicaid enrollees between Kentucky (12 075) and Nebraska (6). Among Medicare enrollees in 2018, family medicine physicians and other primary care providers were the top buprenorphine prescribers. This study not only identified overall increases in buprenorphine availability but also pronounced state-level differences. Such geographic analysis can be used to discern which public policies and regional factors impact buprenorphine access.

Pronounced Declines in Meperidine in the US: Is the End Imminent?

Background: Once a widely used analgesic in the United States (US), meperidine offered an alternative opioid to other opioids as a pain reliever and was widely assumed to be safer with acute pancreatitis. However, within the last two decades meperidine, has gone from a frequently used drug to being used only when patients exhibit atypical reactions to opioids (e.g., morphine and hydromorphone), to being taken off the World Health Organization List of Essential Medications and receiving strong recommendations for overall avoidance. The aim of this study was to identify changes in meperidine distribution in the US, and regional disparities as reported to the Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (DEA ARCOS) and Medicaid. Methods: Data related to meperidine distribution was obtained through ARCOS (2001−2021) and Medicaid public use files (2016−2021). Heat maps were used to visualize regional disparities in distribution by state. States outside a 95% confidence interval were statistically significant. Results: Meperidine distribution between 2001 and 2021 decreased by 97.4% (R = −0.97, p < 0.0001). There was a 34-fold state-level difference in meperidine distribution between Arkansas (16.8 mg/10 persons) and Connecticut (0.5 mg/10 persons) in 2020. Meperidine distribution in 2020 was elevated in Arkansas, Mississippi, and Alabama. In 2021, meperidine distribution was highest in Arkansas (16.7 mg/10 persons) and lowest in Connecticut (0.8 mg/10 persons). Total prescriptions of meperidine as reported by Medicaid decreased by 73.8% (R = −0.67, p = 0.045) between 2016 and 2021. Conclusion: We observed a decrease in the overall distribution of meperidine in the past two decades, with a similar recent decline in prescribing it to Medicaid enrollees. The shortage of some parenteral formulations is an important contributor to these declines, however, the most likely explanation for this global decline in use is related to an increased recognition of safety concerns related to important drug interactions and a neurotoxic metabolite. This data may reflect plans to phase out the use of this opioid, especially in the many situations where safer and more preferred opioids are available.

Peripartum and Postpartum Analgesia and Pain in Women Prescribed Buprenorphine for Opioid Use Disorder Who Deliver by Cesarean Section.

Aim: Little is known about whether pain can be effectively managed in pregnant women with opioid use disorder (OUD) during delivery hospitalization, particularly those undergoing surgery and taking buprenorphine as medication for OUD (MOUD). To address this question, we compared pain scores and opioid analgesic utilization during delivery hospitalization in women taking their pre-hospital dose of buprenorphine who delivered by cesarean section to matched controls. To inform future research efforts, we also began to explore opioid analgesic utilization and pain scores by type of anesthesia as this variable is often not included in related literature. Methods: Retrospective matched cohort study of 46 women prescribed buprenorphine during pregnancy who delivered by cesarean section during a 7-year period. Results: When compared to matched controls, women taking their pre-hospital dose of buprenorphine undergoing cesarean section utilized more opioid analgesics as measured by morphine milligram equivalents (MME) (mean MME first 48 hours 153.0 mg vs 175.1 mg, respectively, P < .01) but had similar pain scores during delivery hospitalization. There was no difference in MME utilization by maternal dose of buprenorphine though sample sizes were small. Women on buprenorphine who received spinal anesthesia with morphine had mean pain scores that were 1.4 points lower (P = .01) during the first 48 hours than women on buprenorphine receiving other methods of anesthesia. Discussion And Conclusions: Pregnant women taking their pre-hospital dose of buprenorphine throughout their surgical delivery hospitalization were able to achieve pain relief similar to women not on MOUD but had higher MME requirements. Our results add to the emerging body of evidence suggesting that individuals on MOUD can achieve adequate post-surgical pain management without adjusting their pre-hospital dose of buprenorphine. Further research is required to fully understand the optimal buprenorphine dosing regimen during surgical hospitalizations. Our results also provide important preliminary evidence that spinal anesthesia containing opioids can be used effectively in individuals with OUD requiring surgical intervention.

Examination of multiple drug arrests reported to the Maine Diversion Alert Program.

PURPOSE: Much of the responsibility for the increasing drug overdoses in the US has been attributed to opioids but most opioid overdoses also involve another drug. The objective of this study was to identify the drugs involved in polysubstance arrests. The substances that were more likely to be found in conjunction with other substances, using the drug arrests reported to Maine's Diversion Alert Program (DAP) were examined. METHODS: Single and multiple drug arrests were quantified (N = 9,216). Multiple drug arrest percentages were compared to single drug arrest percentages to create a Multiple-to-Single Ratio (MSR) specific to each drug family and each drug to identify over (MSR > 1) and under-representation (MSR < 1). RESULTS: Over three-fifths (63.8%) of all arrests involved a single drug. Opioids accounted for over-half (53.5%) of single arrests, followed by stimulants (27.7%) and hallucinogens (7.7%). Similarly, nearly two-fifths (39.6%) of multiple arrests were for opioids, followed by stimulants (30.8%) and miscellaneous (13.0%). Miscellaneous psychoactive prescription substances (e.g. clonidine, gabapentin, cyclobenzaprine, hydroxyzine) had the highest (1.51) MSR of any drug family. Conversely, stimulants (0.63), opioids (0.42), and hallucinogens (0.35) were significantly underrepresented in polysubstance arrests. Carisoprodol (8.80), amitriptyline (6.34), and quetiapine (4.69) had the highest MSR. Bath-salts (0.34), methamphetamine (0.44), and oxycodone (0.54) had the lowest MSR. CONCLUSION: The misuse of opioids, both alone and in conjunction with another drug, deserves continued surveillance. In addition, common prescription drugs with less appreciated misuse potential, especially carisoprodol, amitriptyline, and quetiapine, require greater attention for their ability to enhance the effects of other drugs.

Stimulant Prescribing Error Assessment Rubric Development.

OBJECTIVE: Stimulant medications are used to treat attention-deficit/hyperactivity disorder (ADHD) in adults. However, stimulants are among the most frequently prescribed medications that have a potential to be used nonmedically. We sought to define types of errors associated with treatment of ADHD in adults and to describe a classification rubric for stimulant-related prescribing faults. METHODS: An expert panel conducted a scoping review of the literature and rubric development. The literature search including relevant English language publications indexed in Medline (1990-present, human) and Embase (1990-present, human). In addition, we reviewed relevant documentation such as medication labels and guides containing information related to medications used for the treatment of adult ADHD. The initial version draft rubric was developed by adapting an existing framework for prescribing errors. The expert panel further defined a classification rubric and developed error subcategories, classifications, and descriptions. RESULTS: Two error categories were identified. Category 1 errors are errors resulting from prescribing faults, which further included errors in decision making/judgment; errors related to monitoring for potential harm of stimulants; possible errors: events that should generally be avoided or be used with caution; and suboptimal prescribing. Category 2 errors result from prescription writing, further defined as failure to communicate essential information and transcription errors. CONCLUSIONS: This study provides a comprehensive description of medication errors associated with stimulant and related medications. Our findings have the potential to assist decision making and to tailor delivery programs, recommendations, guidelines, and clinical decision support health information technology on stimulant prescribing and monitoring.

Declines and regional variation in opioid distribution by U.S. hospitals.

ABSTRACT: The United States is enduring a preventable opioid crisis, particularly involving a population being treated in a hospital setting, a subset of whom may escalate to illicit opioids. This project analyzed trends in distribution of opioids by hospitals in the United States. Opioids monitored included buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, oxymorphone, powdered opium, remifentanil, and tapentadol. The Automation of Reports and Consolidated Orders System (ARCOS) reports on substances controlled by the Drug Enforcement Administration. National data from ARCOS reports 5 and 7 from 2000 to 2019 were used for an observational study on hospital opioid distribution. Morphine milligram equivalents (MMEs) were calculated using oral conversion factors. The MME per person per state was calculated to compare data from the peak year, 2012, with data from 2019. Opioid use peaked in 2012, with a -46.6% decline from 2012 to 2019. Half (25) of the states have seen a decrease of -50% or greater. Of the opioid compounds observed, buprenorphine has seen increased (+122.5%) hospital use from 2012 to 2019. All other opioids have been experiencing a decline (≥50%), particularly hydromorphone (-49.9%), oxymorphone (-57.7%), methadone (-58.7%), morphine (-66.9%), codeine (-67.5%), and meperidine (-77.6%). There was a 6-fold difference in population-corrected use of opioids in 2019 between the lowest (6.8 MME/person in New Jersey) and highest (Alaska = 39.6) states. This study demonstrates the considerable progress made thus far by hospitals in curbing the U.S. opioid crisis.

Safety of ECT in patients receiving an oral anticoagulant.

INTRODUCTION: This study assessed the use, tolerability, and safety of anticoagulation via direct oral anticoagulants or warfarin in medical and psychiatric inpatients receiving ECT. METHODS: This retrospective cohort study included 32 patients who received ECT while on either a direct oral anticoagulant (9) or warfarin (23) and spanned 247 encounters at Maine Medical Center between December 2012 and December 2018. Data are presented descriptively and analyzed using SPSS version 25 and Microsoft Excel version 2016. RESULTS: Among the 247 ECT patient encounters, there were few major adverse effects of ECT in this medically complex population. These adverse effects included headache during 4 encounters (1.6%), respiratory distress during 2 encounters (0.8%) and a cardiovascular event during 1 encounter (0.4%). One patient (3.1%) who was receiving concurrent rivaroxaban and venlafaxine experienced gastrointestinal bleeding that was determined to be unrelated to ECT. One patient on fluoxetine and warfarin experienced hemoptysis thought to be secondary to epistaxis. No other major bleeding or clotting event occurred during an ECT session nor for the duration of the hospitalization. DISCUSSION: Direct oral anticoagulants and warfarin appear safe in the treatment of patients with atrial fibrillation or acute venous thromboembolism who are receiving concomitant ECT. Prospective studies are needed to confirm these findings.

Declines and pronounced regional disparities in meperidine use in the United States.

There have been increasing concerns about adverse effects and drug interactions with meperidine. The goal of this study was to characterize meperidine use in the United States. Meperidine distribution data were obtained from the Drug Enforcement Administration's Automated of Reports and Consolidated Orders System. The Medicare Part D Prescriber Public Use File was utilized to capture overall trends in national prescriptions in this observational report. Nationally, meperidine distribution decreased by 94.6% from 2001 to 2019. In 2019, Arkansas, Alabama, Oklahoma, and Mississippi saw significantly greater distribution when compared with the US state average of 9.27 mg per 10 persons (SD = 6.82). Meperidine distribution showed an 18-fold difference between the highest state (Arkansas = 36.8 mg) and lowest state (Minnesota = 2.1 mg). Five of the six states with the lowest distribution were in the Northeast. Meperidine distribution per state was correlated with the prevalence of adult obesity (r(48) = +0.48, p < .001). Family medicine and internal medicine physicians accounted for 28.9% and 20.5%, respectively, of meperidine total daily supply (TDS) in 2017. Interventional pain management (5.66) and pain management (3.48) physicians accounted for the longest TDS per provider. The use of meperidine declined over the last two decades. Meperidine varied by geographic region with south-central states, and those with more obesity, showing greater distribution. Primary care doctors continue to account for the majority of meperidine daily supply. Increasing knowledge of meperidine's undesirable adverse effects like seizures and serious drug-drug interactions is likely responsible for these pronounced reductions.

Methadone bioavailability and dose conversion implications with intravenous and enteral administration: A scoping review.

PURPOSE: Despite its availability for more than 70 years, many details concerning methadone remain contentious, such as the dosing equivalents for intravenous and enteral administration. A scoping review was performed to evaluate whether existing literature on methadone bioavailability in human subjects support the current recommendation that an equivalent enteral dose is twice the intravenous dose. METHODS: A librarian-assisted search of the PubMed and EMBASE databases identified all English-language articles with the terms methadone and bioavailability and/or conversion in the title or abstract published from inception though December 2019. A manual search of references was also performed to identify any additional articles. Studies were included in a scoping review if they were published in English and evaluated methadone bioavailability in human subjects. RESULTS: Among 65 publications initially identified, 6 studies involving a total of 50 patients were included in the review. Bioavailability data for healthy volunteers and patients with opioid use disorder, metastatic cancer, chronic pain from malignant or nonmalignant disease were available for analysis. The pooled mean (95% confidence interval) bioavailability (F) was 85.4% (75.2%-95.6%), with heterogeneity (I2) of 0. In the 4 studies that provided individual patient-level data, F was >50% in 40 of 42 patient measurements (95.2%) and ≥75% in 33 of 42 patient measurements (78.6%). CONCLUSION: Available evidence suggests the bioavailability of methadone is generally more than 75%, there is limited evidence for the currently recommended 1:2 ratio (intravenous:enteral), and a more appropriate dosing ratio may be 1:1.3. This scoping review underscores the need for further research to establish an effective and safe ratio when converting between intravenous and enteral dosing formulations of methadone.

Leveraging pharmacists to maintain and extend buprenorphine supply for opioid use disorder amid COVID-19 pandemic.

PURPOSE: Strategies for deploying clinical pharmacists to increase access to buprenorphine in inpatient, outpatient and transitional care, and community practice settings are described. SUMMARY: Access to medications for opioid use disorder (MOUD) is essential, but patients face many barriers when pursuing treatment and MOUD. The coronavirus disease 2019 (COVID-19) pandemic has compounded the opioid crisis and worsened outcomes by introducing new barriers to MOUD access. Many strategies to ensure continued access to MOUD have been described, but the role of leveraging pharmacists during the opioid/COVID-19 syndemic to improve medication access and outcomes remains underappreciated. Pharmacists, while both qualified and capable of liberalizing access to all forms of MOUD, may have the strongest impact by increasing access to buprenorphine. Herein, we present progressive strategies to maintain and extend buprenorphine access for patients with OUD through deployment of clinical pharmacists, particularly in the context of the COVID-19 pandemic, during which access may be further restricted. CONCLUSION: Leveraging pharmacists to extend access to MOUD, particularly buprenorphine, remains an underutilized strategy that should be implemented, particularly during the concurrent COVID-19 global pandemic.

Prescription Opioid Distribution after the Legalization of Recreational Marijuana in Colorado.

There have been dynamic changes in prescription opioid use in the US but the state level policy factors contributing to these are incompletely understood. We examined the association between the legalization of recreational marijuana and prescription opioid distribution in Colorado. Utah and Maryland, two states that had not legalized recreational marijuana, were selected for comparison. Prescription data reported to the Drug Enforcement Administration for nine opioids used for pain (e.g., fentanyl, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone) and two primarily for opioid use disorder (OUD, methadone and buprenorphine) from 2007 to 2017 were evaluated. Analysis of the interval pre (2007-2012) versus post (2013-2017) marijuana legalization revealed statistically significant decreases for Colorado (P < 0.05) and Maryland (P < 0.01), but not Utah, for pain medications. There was a larger reduction from 2012 to 2017 in Colorado (-31.5%) than the other states (-14.2% to -23.5%). Colorado had a significantly greater decrease in codeine and oxymorphone than the comparison states. The most prevalent opioids by morphine equivalents were oxycodone and methadone. Due to rapid and pronounced changes in prescription opioid distribution over the past decade, additional study with more states is needed to determine whether cannabis policy was associated with reductions in opioids used for chronic pain.

Rise and regional disparities in buprenorphine utilization in the United States.

PURPOSE: Buprenorphine is an opioid partial agonist used to treat opioid use disorder. While several policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution of the medication. METHODS: The amount of buprenorphine distributed from 2007 to 2017 was obtained from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System. Data were expressed as the percent change and milligrams per person in each state. The formulations and cost for prescriptions covered by Medicaid (2008 to 2018) were also examined. RESULTS: Buprenorphine distributed to pharmacies increased about 7-fold (476.8 to 3179.9 kg) while the quantities distributed to hospitals grew 5-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of physicians authorized to prescribe buprenorphine and distribution per state (r[49] = +0.94, P < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but accounted for less than three-fifth (57.3% of 6.56 million prescriptions) in 2018. CONCLUSIONS: Although buprenorphine availability has substantially increased over the last decade, distribution was very nonhomogeneous across the United States.

Quantification of Conflicts of Interest in an Online Point-of-Care Clinical Support Website.

Online medical reference websites are utilized by health care providers to enhance their education and decision making. However, these resources may not adequately reveal pharmaceutical-author interactions and their potential conflicts of interest (CoIs). This investigation: (1) evaluates the correspondence of two well-utilized CoI databases: the Centers for Medicare and Medicaid Services Open Payments (CMSOP) and ProPublica's Dollars for Docs (PDD) and (2) quantifies CoIs among authors of a publicly available point of care clinical support website which is used to inform evidence-based medicine decisions. Two data sources were used: the hundred most common drugs and the top fifty causes of death. These topics were entered into a freely available database. The authors (N = 139) were then input into CMSOP and PDD and compensation and number of payments were determined for 2013-2015. The subset of highly compensated authors that also reported "Nothing to disclose" were further examined. There was a high degree of similarity between CMSOP and PDD for compensation (R2 ≥ 0.998) and payment number (R2 ≥ 0.992). The amount received was 1.4% higher in CMSOP ($4,059,194) than in PDD ($4,002,891). The articles where the authors had received the greatest compensation were in neurology (Parkinson's Disease = $1,810,032), oncology (Acute Lymphoblastic Leukemia = $616,727), and endocrinology (Type I Diabetes = $377,388). Two authors reporting "Nothing to disclose" received appreciable and potentially relevant compensation. CMSOP and PDD produced almost identical results. CoIs were common among authors but self-reporting may be an inadequate reporting mechanism. Recommendations are offered for improving the CoI transparency of pharmaceutical-author interactions in point-of-care electronic resources.

Dynamic changes in prescription opioids from 2006 to 2017 in Texas.

BACKGROUND: The US is experiencing an epidemic of opioid overdoses which may be at least partially due to an over-reliance on opioid analgesics in the treatment of chronic non-cancer pain and subsequent escalation to heroin or illicit fentanyl. As Texas was reported to be among the lowest in the US for opioid use and misuse, further examination of this state is warranted. MATERIALS AND METHODS: This study was conducted to quantify prescription opioid use in Texas. Data was obtained from the publicly available US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) which monitors controlled substances transactions from manufacture to commercial distribution. Data for 2006-2017 from Texas for ten prescription opioids including eight primarily used to relieve pain (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, morphine, oxycodone, oxymorphone) and two (buprenorphine and methadone) for the treatment of an Opioid Use Disorder (OUD) were examined. RESULTS: The change in morphine mg equivalent (MME) of all opioids (+23.3%) was only slightly greater than the state's population gains (21.1%). Opioids used to treat an OUD showed pronounced gains (+90.8%) which were four-fold faster than population growth. Analysis of individual agents revealed pronounced elevations in codeine (+387.5%), hydromorphone (+106.7%), and oxycodone (+43.6%) and a reduction in meperidine (-80.3%) in 2017 relative to 2006. Methadone in 2017 accounted for a greater portion (39.5%) of the total MME than hydrocodone, oxycodone, morphine, hydromorphone, oxymorphone, and meperidine, combined. There were differences between urban and rural areas in the changes in hydrocodone and buprenorphine. CONCLUSIONS: Collectively, these findings indicate that continued vigilance is needed in Texas to appropriately treat pain and an OUD while minimizing the potential for prescription opioid diversion and misuse. Texas may lead the US in a return to pre-opioid epidemic prescription levels.

Increasing heroin, cocaine, and buprenorphine arrests reported to the Maine Diversion Alert Program.

BACKGROUND: The opioid overdose crisis is especially pronounced in Maine. The Diversion Alert Program (DAP) was developed to combat illicit drug use and prescription drug diversion by facilitating communication between law enforcement and health care providers with the goal of limiting drug-related harms and criminal behaviors. Our objectives in this report were to analyze 2014-2017 DAP for: (1) trends in drug arrests and, (2) differences in arrests by offense, demographics (sex and age) and by region. METHODS: Drug arrests (N=8193, 31.3% female, age=33.1±9.9) reported to the DAP were examined by year, demographics, and location. RESULTS: The most common substances of the 10,064 unique charges reported were heroin (N=2203, 21.9%), crack/cocaine (N=945, 16.8%), buprenorphine (N=812, 8.1%), and oxycodone (N=747, 7.4%). While the overall number of arrests reported to the DAP declined in 2017, the proportion of arrests involving opioids (heroin, buprenorphine, or fentanyl) and stimulants (cocaine/crack cocaine, or methamphetamine), increased (p<.05). Women had significantly increased involvement in arrests involving sedatives and miscellaneous pharmaceuticals (e.g. gabapentin) while men had an elevation in stimulant arrests. Heroin accounted for a lower percentage of arrests among individuals age >60 (6.6%) relative to young-adults (18-29, 22.3%, p<.0001). Older-adults had significantly more arrests than younger-adults for oxycodone, hydrocodone, and marijuana. CONCLUSION: Heroin had the most arrests from 2014 to 2017. Buprenorphine, fentanyl and crack/cocaine arrests increased appreciably suggesting that improved treatment is needed to prevent further nonmedical use and overdoses. The Diversion Alert Program provided a unique data source for research, a harm-reduction tool for health care providers, and an informational resource for law enforcement.

Addressing clozapine under-prescribing and barriers to initiation: a psychiatrist, advanced practice provider, and trainee survey.

Clozapine use has declined, despite its superior antipsychotic efficacy in treatment-resistant schizophrenia. Implications for clozapine underutilization include suboptimal treatment outcomes and increased hospitalizations. Many barriers preventing the use of clozapine have been described in the literature, including suboptimal knowledge and poor perceptions. The aim of this study was to assess psychiatry prescribers' perception and knowledge of clozapine. A survey was distributed to advanced practice providers, psychiatrists, and trainees (i.e. residents and fellows) at 10 medical centers within the US and Canada. The survey asked respondents about their perception of clozapine use and assessed their pharmacotherapeutic knowledge of clozapine. Two hundred eleven individual submitted completed surveys of a possible 1152; a response rate of 18.3%. There were no statistically significant differences between the advanced practice provider plus psychiatrist groups and the trainee group for most perception (eight of nine) and knowledge (eight of nine) questions. The knowledge questions with the lowest scores pertained to clozapine reinitiation and myocarditis. The majority of all respondents (144, 68.2%) felt that clozapine prescribing was a burden. Findings of this study support the need for continued clozapine education regardless of a prescriber's age/experience. Future studies to assess barriers to clozapine prescribing should extend beyond academic centers.

Descriptive, observational study of pharmaceutical and non-pharmaceutical arrests, use, and overdoses in Maine.

OBJECTIVES: The Maine Diversion Alert Program grants healthcare providers access to law enforcement data on drug charges. The objectives of this report were to analyse variations in drug charges by demographics and examine recent trends in arrests, prescriptions of controlled substances and overdoses. DESIGN: Observational. SETTING: Arrests, controlled prescription medication distribution and overdoses in Maine. PARTICIPANTS: Drug arrestees (n=1272) and decedents (n=2432). PRIMARY OUTCOME MEASURES: Arrestees were analysed by sex and age. Substances involved in arrests were reported by schedule (I-V or non-controlled prescription) and into opioids, stimulants or other classes. Controlled substances reported to the Drug Enforcement Administration (2007-2017) were evaluated. Drug-induced deaths (2007-2017) reported to the medical examiner were examined by the substance(s) identified. RESULTS: Males were more commonly arrested for stimulants and schedule II substances. More than two-thirds of arrests involved individuals under the age of 40. Individuals age >60 were elevated for oxycodone arrests. Over three-fifths (63.38%) of arrests involved schedule II-IV substances. Opioids accounted for almost half (44.6%) of arrests followed by stimulants (32.5%) and sedatives (9.1%). Arrests involving buprenorphine exceeded those for oxycodone, hydrocodone, methadone, tramadol and morphine, combined. Prescriptions for hydrocodone (-56.0%) and oxycodone (-46.9%) declined while buprenorphine increased (+58.1%) between 2012 and 2017. Deaths from 2007 to 2017 tripled. Acetylfentanyl and furanylfentanyl were the most common fentanyl analogues identified. CONCLUSIONS: Although the overall profile of those arrested for drug crimes in 2017 involve males, age <40 and heroin, exceptions (oxycodone for older adults) were observed. Most prescription opioids are decreasing while deaths involving opioids continue to increase in Maine.