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Alyssa M Peckham, Maria J Ananickal, David A Sclar Department of Pharmacy Practice, Midwestern University College of Pharmacy-Glendale, Glendale, AZ, USA Abstract: The abuse potential of gabapentin is well documented; with gabapentin having been noted as an agent highly sought after for use in potentiating opioids. When combined with opioids, the risk of respiratory depression and opioid-related mortality increases significantly. In the US, gabapentin was approved by the Food and Drug Administration as a non-controlled substance. To date, and in spite of empirical evidence suggestive of diversion and abuse with opioids, gabapentin remains a non-controlled substance at the federal level. This has forced individual US states and jurisdictions – often significantly impacted by the opioid epidemic – to forge ahead with legislative initiatives designed to reclassify and/or monitor the use of gabapentin. Since August 1, 2016, 14 of 51 US states and jurisdictions have either implemented legislative mandates requiring pharmacovigilance programs, amended rules and regulations, are in the throes of crafting policy, or are in the midst of gathering additional data for decision making. This fragmented geographic approach yields only a modest benefit in combating the abuse of gabapentin and/or the national opioid epidemic. Herein, we report state-by-state efforts to enhance pharmacovigilance and call for a re-evaluation of the schedule status of gabapentin at the federal level, and design and implementation of a national pharmacovigilance program. Keywords: gabapentin, prescription drug abuse, opioids, pharmacovigilance, health policy

Background: Gabapentinoids (gabapentin and pregabalin) are widely used in clinical practice, but recent evidence indicates that they carry an increased risk of misuse. As healthcare professionals (HCPs) and policymakers plan different strategies to promote harm reduction, it is important to understand different interested party viewpoints., Objective: To explore prescriber, pharmacist, and drug policy expert (DPE) awareness, opinions, and experiences regarding gabapentinoid misuse., Methods: A qualitative description study using individual semi-structured virtual interviews was conducted between February and April 2021. Participants included prescribers (physicians, physician assistants [PA], or nurse practitioners [NP]) and pharmacists practicing in outpatient, ambulatory, or community-based healthcare settings; individuals with relevant drug policy expertise were also included. Qualtrics (Provo, Utah) and Zoom (San Jose, California) were used to facilitate quantitative (for initial screening and participant characteristics) and qualitative (interview) data collection. Data were coded and organized into themes in NVivo (QSR International; Burlington, Massachusetts) using thematic analysis steps., Results: A total of 43 individuals participated in this study, including 16 (37.2%) pharmacists, 13 (30.2%) physicians, seven (16.3%) NPs, four (9.3%) DPEs, two (4.7%) pharmacist/DPEs, and one (2.3%) PA. Results were organized along four themes: (1) challenges/opportunities in gabapentinoid use; (2) gabapentinoid misuse awareness; (3) solutions to gabapentinoid misuse and (4) contributing barriers in pain management. Participants invoked different opinions in their consideration of gabapentinoid misuse, including the desire for harm reduction, the limitations of the current healthcare and insurance system, the lack of options for pain and substance use disorder treatment, and the influence of patient expectations., Conclusions: Gabapentinoid misuse was commonly framed in comparative fashion to ongoing concerns with opioids, and proposed solutions often focused less on regulatory control and more toward patient and HCP education and an overhaul of the health system approach to substance use and healthcare overall., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Monthly extended-release buprenorphine subcutaneous injection (BUP-XR) is a newer treatment formulation for use in moderate to severe opioid use disorder. After injection into the subcutaneous tissue of the abdomen, the medication forms a depot to allow for slow release of buprenorphine. As such, a small yet visible and palpable nodule is normal and is expected to decrease in size over the following weeks to months. Given the newness of this medication, it is possible that not all healthcare providers are familiar with this formulation, nor will they interpret the BUP-XR depot as normal findings. Herein, we provide a case report where a patient's BUP-XR depot was misdiagnosed as an abscess, resulting in incision and drainage and disruption of life-saving opioid use disorder treatment. To prevent cases like this in the future, it is important that providers administering BUP-XR properly educate patients on what to expect during treatment with BUP-XR and when to seek care for potential abnormalities. In addition, it is critical that healthcare providers working in other treatment settings are aware of how to properly evaluate BUP-XR injection sites., Competing Interests: LGK has been on Indivior advisory board and a nonbranded speaker’s panel. AMP is also a salaried employee of Otsuka Pharmaceutical Development and Commercialization, Inc. The other authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Background: Prompt access to prescribed buprenorphine/naloxone films (BUP/NX) and naloxone nasal spray (NNS) is vital for patients with opioid use disorder (OUD), but multiple studies have documented pharmacy-level barriers., Methods: A cross-sectional secret shopper telephone audit was conducted in a sample of 5734 actively licensed pharmacies in 11 U.S. states from May 2020-April 2021. Primary outcomes included availability of 14 generic BUP/NX 8/2 mg and one unit of NNS 4 mg. Outcomes were compared by pharmacy type, county metropolitan status, state Medicaid expansion status, and state drug overdose death rate., Results: Data from 4984 pharmacies (3402 chain and 1582 independent) were analyzed. Both medications were available in 41.2 % of pharmacies, BUP/NX was available in 48.3%, and NNS was available in 69.5%. Chain pharmacies were significantly more likely than independent pharmacies to have both medications available, to have each medication available individually, and to be willing to order BUP/NX. Pharmacies in metropolitan counties were more likely to have BUP/NX available than pharmacies in non-metropolitan counties, pharmacies in Medicaid expansion states were more likely to have both medications available and to have NNS available than pharmacies in non-expansion states, and pharmacies in states with high drug overdose death rates were more likely to have NNS available than pharmacies in states with low drug overdose death rates., Conclusions: BUP/NX and NNS are not readily accessible in many U.S. pharmacies. Deficits in access are most pronounced in independent pharmacies, though county- and state-level factors may also influence availability of these essential medications., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abstract: Low dose buprenorphine initiation, is an alternative method of initiating buprenorphine in which the starting dose is very low and gradually increased to therapeutic levels over a period of days. This method takes advantage of slow displacement of the full opioid agonist from mu-opioid receptors, avoiding the need for a person with opioid use disorder to experience opioid withdrawal symptoms before initiating buprenorphine, while also minimizing the risk of precipitated opioid withdrawal. With this initiation method, full opioid agonists can be continued as buprenorphine is initiated, expanding the population to which buprenorphine can be offered. To date, the literature on low dose initiation is primarily case-based but rapidly growing. While evidence emerges, guidance for the use of low dose initiation is clearly desired and urgently needed in the context of an increasingly risky and contaminated opioid drug supply, particularly with high potency synthetic opioids, driving overdose deaths. Despite limited evidence, several principles to guide low dose initiation have been identified including: (1) choosing the appropriate clinical situation, (2) initiating at a low buprenorphine dose, (3) titrating the buprenorphine dose gradually, (4) continuing the full opioid agonist even if it is nonmedical, (5) communicating clearly with frequent monitoring, (6) pausing or delaying buprenorphine dose changes if opioid withdrawal symptoms occur, and (7) prioritizing care coordination. We review a practical approach to low dose initiation in hospital-based and outpatient settings guided by the current evidence., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American Society of Addiction Medicine.)

Purpose: Gabapentin misuse is on the rise and has forced many US states to mobilize policies to address this public health concern. The purpose of this manuscript is to update state-level gabapentin misuse-related policies in the US through September 1, 2021, discuss the benefits and risks of current measures, and highlight gaps in national response., Methods: Identification of state and federal district policy changes and deliberations related to gabapentin were searched via internet for all 50 states and 1 federal district (n = 51). Only results from state regulatory bodies, such as the board of pharmacy, or state legislative bodies, such as the senate, were considered for inclusion., Results: Results showed that 22 states and federal districts (43.1%) tightened regulation, while another 2 (3.9%) are considering doing so. Of the 22 states and federal districts with policy changes, 15 (68.2%) enrolled gabapentin into their prescription drug monitoring program, while 7 (31.8%) reclassified gabapentin as a Schedule V controlled substance (C-V)., Conclusion: Absent of federal guidance surrounding gabapentin misuse, the onus has fallen on individual states; thus, approaches have ranged from no intervention to reclassification as a C-V. These measures aim to reduce medication supply but fall short of addressing patient outcomes and reducing harm. Therefore, harm reduction-informed public health policies must be implemented to positively impact patient outcomes and enhance safety., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Research has shown buprenorphine/naloxone to be an effective medication for treating individuals with opioid use disorder. At the same time, treatment discontinuation rates are reportedly high though much of the extant evidence comes from studies of the Medicaid population., Objectives: To examine the pattern and determinants of buprenorphine/naloxone treatment discontinuation in a population of commercially insured individuals., Research Design: We performed a retrospective observational analysis of Massachusetts All Payer Claims Data (MA APCD) covering years 2013 through 2017. We defined treatment discontinuation as a gap of 60 consecutive days without a prescription for buprenorphine/naloxone within a time frame of 24 months from the initiation of treatment. A mixed-effect Cox proportional hazard model examined the associated risk of discontinuing treatment with baseline predictors., Subjects: A total of 5134 individuals who were commercially insured during the study period., Measures: Buprenorphine/naloxone treatment discontinuation., Results: Overall 75% of individuals had discontinued treatment within two years of initiating treatment, and median time to discontinuation was 300 days. Patients aged between 18 and 24 years (HR = 1.436, 95%, CI = 1.240-1.663) and receiving treatment from prescribers with high panel-size (HR = 1.278, 95% CI = 1.112-1.468) had higher risk of discontinuing treatment. On the contrary, patients receiving treatment from multiple prescribers had lower associated risk of treatment discontinuation., Conclusions: A substantial percentage of patients discontinue treatment well before they can typically meet criteria for sustained remission. Further investigations should assess the clinical outcomes following premature discontinuation and identify strategies for retaining patients in treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This article will review the epidemiology and pharmacology of gabapentinoids (gabapentin and pregabalin) relevant to their emerging misuse potential and provide guidance for clinical and regulatory management. Gabapentinoids are γ-aminobutyric acid analogues that produce their therapeutic effects by inhibiting voltage-gated calcium channels and decreasing neurotransmitter release. Recently gabapentinoid prescribing and use have increased tremendously. Although traditionally thought to possess a favorable safety profile, gabapentinoid misuse has also risen significantly. Gabapentinoid misuse generally occurs in combination with other substances, most notably opioids, and may be for purposes of eliciting euphoric effects, enhancing the effects of other substances, or self-treating conditions such as withdrawal, pain, anxiety, or insomnia. Given its faster onset, increased bioavailability and potency, and nonsaturable absorption, pregabalin's pharmacokinetics theoretically enhance its misuse liability versus gabapentin. However, gabapentin can produce similar euphoric effects, and epidemiologic studies have identified higher rates of gabapentin misuse in the United States, likely because of greater availability and less regulated prescribing. Although adverse events of gabapentinoid-only ingestion are relatively benign, a growing body of evidence indicates that gabapentinoids significantly increase opioid-related morbidity and mortality when used concomitantly. In addition, significant withdrawal effects may occur on abrupt discontinuation. As a result of these trends, several US states have begun to further regulate gabapentinoid prescribing, reclassifying it as a controlled substance or mandating reporting to local prescription drug-monitoring programs. Although increased regulation of gabapentin prescribing may be warranted, harm reduction efforts and increased patient and provider education are necessary to mitigate this concerning gabapentinoid misuse trend., (© 2021, The American College of Clinical Pharmacology.)

Background Reports of gabapentinoid (gabapentin and pregabalin) misuse are on the rise, but few studies have assessed this within the general US population. Objective Describe lifetime misuse/abuse/non-prescribed obtainment of gabapentinoids and descriptive characteristics associated with such actions in a US general population sample. Setting This cross-sectional questionnaire was administered online by Qualtrics ® research panel aggregator via quota-based sampling. Methods Data were collected from a sample of respondents that mirrored the general US population aged 18-59 years with regards to age, geographic region, ethnicity, income, and education level, based on most recent census data. Misuse/abuse/non-prescribed obtainment was collectively defined as use of a gabapentinoid for reasons other than a diagnosed medical condition, using with the intention of altering one's state of consciousness, or obtaining without a prescription. A multivariable logistic regression model was created to predict misuse/abuse/non-prescribed obtainment of gabapentinoids, incorporating relevant covariates. Main outcome measure Proportion of sample indicating lifetime misuse/abuse/non-prescribed obtainment of gabapentinoids. Results Among 1,843 respondents, 121 (6.6%) reported gabapentinoid misuse/abuse/non-prescribed obtainment. Specifically, 2.1% (n = 39) and 1.5% (n = 27) of respondents for gabapentin and pregabalin, respectively, met study criteria for abuse. Opioids were the most common medication co-administered with gabapentinoids (among 50-70% of respondents) for misuse/abuse. Previous treatment for addiction (OR: 2.61, 95% CI: 1.32-5.14, p = 0.005) and the total attitudinal risk score (OR: 1.14, 95% CI: 1.09-1.19, p < 0.001) were associated with gabapentinoid misuse/abuse/non-prescribed obtainment. Conclusion Among those surveyed, 6.6% reported previous gabapentinoid misuse/abuse/non-prescribed obtainment, providing one of the first estimates within a nationally distributed, US general population sample., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Introduction: Gabapentin and pregabalin (gabapentinoids) can be given with opioids for opioid-sparing and adjuvant analgesic effects. In the context of certain comorbidities and high dosages, coadministration of these agents can lead to respiratory depression or oversedation, necessitating naloxone administration., Methods: A retrospective chart review from January 2015 to December 2017 was conducted to include patients who received naloxone and opioids with or without gabapentinoids. Exclusion criteria included pregnancy or having received naloxone in the emergency department, intensive care, or pediatrics units. The primary outcome was to characterize differences between groups regarding comorbidities, history of renal or hepatic dysfunction, history of SUD, opioid tolerance, initiation and dose appropriateness of gabapentinoids, and dose intensity of gabapentinoids and opioids. Secondary outcomes were concomitant CNS depressant use and naloxone episodes for documented respiratory depression., Results: Of 126 patients who met inclusion criteria, 36 received opioids and gabapentinoids (gabapentinoid group) and 90 received opioids alone (nongabapentinoid group). There were 136 naloxone episodes between the 2 groups. More than 50% of the naloxone episodes in the gabapentinoid group involved opioids of at least 90 oral morphine mg equivalents. Respiratory depression accounted for 39% and 15.8% of the naloxone episodes in the gabapentinoid and nongabapentinoid groups, respectively., Discussion: There may be increased naloxone episodes among patients receiving opioids and gabapentinoids. Future studies are needed to evaluate the incremental risk of respiratory depression and oversedation as it pertains to concomitant medication administration and patient-specific factors., Competing Interests: Disclosures: O.T. has a current affiliation with GSK. The other authors have no conflicts of interest to disclose., (© 2021 CPNP. The Mental Health Clinician is a publication of the College of Psychiatric and Neurologic Pharmacists.)

Background: In clinical trial settings, extended-release buprenorphine (XR-BUP) is noninferior to sublingual buprenorphine and may offer some advantages. However, real-world experiences of XR-BUP are limited and outcomes are unknown for low-threshold clinics with high-risk populations. Practical guidance is lacking on overcoming treatment challenges, such as inability for some to stabilize on sublingual (SL) BUP for seven days prior to XR-BUP and ongoing craving/withdrawal symptoms during treatment., Methods: Retrospective case series of a convenience sample of 40 serial adults with opioid use disorder (OUD) treated with XR-BUP from Massachusetts General Hospital bridge clinic from February 1, 2019, to July 31, 2019., Results: Patients were mostly male (67.5%), non-Hispanic white (97.5%), unstably housed (77.5%), and average age of 32.1 years old. The average SL BUP dose prior to XR-BUP was 18.6 mg (standard deviation [SD] = 5; range 8-32) for an average treatment duration of 105 days (SD = 191; range 1-810). Ten (25%) patients received SL BUP for fewer than the seven recommended days (mean = 3.7, SD = 1.4, range = 1-6). Standard induction dosing was administered to 30%, empiric high-dose XR-BUP (300 mg monthly) was administered to 25%, and 55% were treated with supplemental SL BUP ranging from 4 to24mg, daily or as needed, for varying time periods. At the end of data collection, 65% remained on XR-BUP, 30% discontinued XR-BUP, and one patient was lost to follow-up. Acute care utilization rates were similar between patients who continued XR-BUP versus discontinued at 18.5% and 16.6%, respectively (χ 2  = 0.02, p-value = 0.89). Toxicology was negative for other opioids in 65% of patients throughout treatment. There were no reports of overdose, withdrawal after use of opioids, or precipitated withdrawal after subsequent XR-BUP. Patients' most cited reason for discontinuing XR-BUP was a preference for SL BUP., Conclusion: This real-world evaluation of XR-BUP in a low-threshold clinic found that treatment was feasible, well tolerated, and outcomes were good, with most individuals choosing to continue treatment and a majority with no evidence of ongoing opioid use or precipitated withdrawal., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objectives: Gabapentin and pregabalin have been considered relatively safe opioid-sparing adjuncts for pain management. However, rising prescribing trends, presence of gabapentinoids in opioid-related overdoses, and the growing body of evidence regarding gabapentinoid misuse and abuse, have caused gabapentinoids to emerge as a drug class of public health concern. This study aimed to assess the prevalence of, and factors associated with gabapentinoid use and misuse., Methods: This retrospective study of Texas Medicaid data from 1/1/2012 to 30/8/2016 included patients aged 18-63 years at index date, with ≥ 1 gabapentinoid prescription, and continuously enrolled 6 months pre-index and 12 months post-index. Gabapentinoid misuse was defined as ≥ 3 claims exceeding daily doses of 3600 mg for gabapentin and 600 mg for pregabalin. Age, gender, concurrent opioid use, neuropathic pain diagnoses and gabapentinoid type were independent variables. Descriptive and inferential statistics were used., Results: Of included subjects (N = 39,000), 0.2% (N = 81) met study criteria for gabapentinoid misuse. Overall, the majority (76.4%) of gabapentinoid users were aged 41-63 years with a mean ± SD age of 48.2 ± 10.7 years. Those patients meeting the study criteria for gabapentinoid misuse were significantly younger (45.1 ± 11.0 vs 48.2 ± 10.7, p = 0.0084). Majority of the study sample was female (68.1%). However, a significantly higher proportion of males met the study criteria for gabapentinoid misuse compared to females (0.3% vs 0.2%, p = 0.0079). Approximately one-half (51.9%) of the study sample had neuropathic pain, and gabapentinoid misuse was significantly higher in neuropathic pain patients compared to those without neuropathic pain (0.3% vs 0.1%, p = 0.0078). Over three-quarters (77.4%) of patients were using gabapentin; however, gabapentinoid misuse was significantly higher among pregabalin users (0.4% vs 0.2%, p = 0.0003). Approximately 20% (17.3%) of gabapentinoid users had ≥ 90 days of concurrent opioid use. However, there was no significant difference in gabapentinoid misuse among patients with concurrent opioid use compared to patients without (0.3% vs 0.2%, p = 0.1440). Factors significantly associated with misuse included: male sex (odds ratio [OR] 0.486; 95% confidence interval [CI] 0.313-0.756; p = 0.0013); neuropathic pain (OR 2.065; 95% CI 1.289-3.308; p = 0.0026); and pregabalin versus gabapentin use (OR 2.337, 95% CI 1.492-3.661; p = 0.0002). Concurrent opioid use was not significantly associated with gabapentinoid misuse (OR 1.542, 95% CI 0.920-2.586; p = 0.1006)., Conclusion: Prevalence of gabapentinoid misuse was low (0.2%) among Texas Medicaid recipients. Younger age, male gender, neuropathic pain diagnosis and pregabalin use were significantly associated with higher levels of gabapentinoid misuse.

Background: Conventional buprenorphine inductions for OUD are clinically useful but require patients to experience mild to moderate opioid withdrawal symptoms to avoid precipitated withdrawal. This may be intolerable/unreasonable for some, which may have precluded successful buprenorphine treatment in the past. Microdosing buprenorphine, allowing for full agonist opioid overlap, has emerged as a clinically useful strategy for those unable to complete conventional buprenorphine induction. However, many questions remain such as preclusions regarding the amount of full agonist opioid overlap, speed of buprenorphine microdose titration, and overcoming implementation barriers in U.S. hospitals. Case presentation: A female between the ages of 30 and 40 with severe OUD admitted to the hospital for IDU-related osteomyelitis wished to begin buprenorphine for OUD. Her hospitalization was subject to premature discharge at any time due to competing interests of potential foreclosure on her home, so buprenorphine needed to be started rapidly for safety and improved outcomes. Due to her significant acute pain requirements managed with full agonist opioids, it was unreasonable to consider conventional buprenorphine induction. Buprenorphine microdose strategy was employed at more rapid titration and previously described in the literature, starting at 1 mg TDD on day 1, 3 mg TDD on day 2, and 8 mg TDD on day 3 with full agonist opioid overlap starting at 1,944 MME tapered down to 473 MME. The patient prematurely left the hospital, at which time buprenorphine 8 mg TDD was held at this dose for days 3-8 while full agonist opioid was tapered from 473 MME to 117 MME. BUP was then further titrated to 8 mg TID. This patient tolerated buprenorphine microdosing well, without any treatment-emergent opioid symptoms or worsening of baseline symptoms. Discussion: This case demonstrates the success of buprenorphine microdose induction despite very high doses of full agonist opioid overlap and demonstrates the ability to titrate buprenorphine microdoses faster than originally described. Strategies to overcoming implementation barriers are also discussed.

Background and Aims: Research has recommended a combination of pharmacotherapy and behavioral therapy to treat opioid use disorder (OUD) or alcohol use disorder (AUD). The objective of this study was to estimate the prevalence of U.S. outpatient visits in which patients had a documented OUD or AUD and in what proportion of these visits the patient was receiving medication for OUD (MOUD) or AUD (MAUD), alone or in combination with behavioral therapy., Design: Cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) from 2014 to 2016., Setting: NAMCS provides national estimates based on the latest census data, for all U.S. outpatient medical visits., Participants/cases: All visits involving patients aged ≥18 years with an OUD or AUD diagnosis., Measurement: Medications for OUD included buprenorphine, buprenorphine/naloxone, or naltrexone; medications for AUD included acamprosate, disulfiram, or naltrexone. We defined behavioral therapy as provision of psychosocial therapy, mental health counseling, or stress management. We also compared annualized data between 2014 and 2016 using the Chi-square test., Findings: From 2014 to 2016, NAMCS recorded nearly 2.3 billion adult outpatient visits, including 17.1 million and 21.7 million visits involving patients with an OUD or AUD diagnosis, respectively. From 2014 to 2016, a decreased prevalence of annual visits involved AUD (11.7 vs. 9.9/1000, P < 0.0001), while those for OUD increased (9.3 vs. 13.3/1000, P < 0.0001). Among office visits with an OUD diagnosis, a MOUD was documented in 14.2 million (83.1%) visits and behavioral therapy was provided in 4.4 million (25.6%). Among office visits with an AUD diagnosis, an MAUD was documented in approximately 800,000 (3.6%) and behavioral therapy in 5.4 million (24.8%)., Conclusion: These data highlight an opportunity to increase the use of MAUD and offer behavioral therapy to those with OUD and/or AUD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Increased rates of overdose (OD) and blood-borne infections have been associated with injection drug use (IDU). This increasing overlap between IDU-related infectious diseases (ID) is a byproduct of the opioid OD crisis, especially with the transition to synthetic opioids with faster onset and shorter duration leading to potentially more frequent injections. ID specialists are uniquely positioned to positively impact the opioid OD crisis by capitalizing on opportunistic moments of engagement during clinical encounters with people who inject drugs (PWID). Harm reduction services should therefore be expanded and offered to PWID in ID settings to reduce rates of OD, infection, and hospitalization. Major target areas include (1) teaching and distribution of materials related to safer injection practice such as sterile injection supplies, fentanyl test strips, and naloxone; (2) increased screening and access to pre-exposure prophylaxis and postexposure prophylaxis; and (3) initiation of medications for opioid use disorder. Incorporating these strategies in various treatment settings can expand treatment access, improve patient outcomes, and reduce stigma associated with IDU., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Reports of kratom ( Mitragyna speciosa ) use, a medicinal plant widely found in Southeast Asia, are on the rise in the US. However, the prevalence and characteristics of individuals who use kratom in the US is unknown., Objective: To estimate lifetime prevalence of, and descriptive characteristics associated with, kratom use in a sample of the US general population., Methods: A cross-sectional survey was administered online by Qualtrics® research panel aggregator. Utilizing quota-based sampling, data was collected from a US sample aged 18-59 years, representative to age, geographic region, ethnicity, income, and education level. Data was collected regarding respondent demographic/clinical characteristics, as well as frequency/patterns of kratom and other drug use., Results: Among 1,842 respondents, 112 (6.1%) reported use of kratom within their lifetime. Respondents who used kratom were largely between 25-44 years old, male, employed, and at higher educational levels. A total of 24.1% to 47.3% of respondents indicated self-reported diagnoses for addiction, and 42.9% reported having previously received treatment for addiction. A total of 71.4% to 92% of respondents who used kratom also reported use of other drugs, including nicotine, cannabis, cocaine, ecstasy, methamphetamine, and heroin., Conclusions: To our knowledge, this analysis provides the first estimate of kratom use in the general US population, providing insight on demographic/clinical characteristics of individuals reporting use.

Background: As opioid-related overdose deaths climb in the U.S., risk reduction measures are increasingly important. One such measure recommended involves provision of proactive substance use counseling regarding the risks of opioid analgesics. This is particularly important in patients at increased risk of overdose, such as those with substance use disorders (SUD) or those receiving concomitant medications that further increase the overdose risk (eg, benzodiazepines, gabapentinoids, or Z-hypnotics). However, previous research regarding the likelihood that such counseling is provided during outpatient prescriber visits is lacking., Objectives: To determine the percentage of U.S. ambulatory care visits in which patients taking prescription opioids received substance use counseling, and whether counseling was more common in patients with concomitant GABAergic medication(s) (benzodiazepine, gabapentinoid or Z-hypnotic) or substance use disorder (SUD) diagnosis., Methods: A cross-sectional analysis was conducted of all patients aged ⩾18 years identified as having a prescription opioid on their medication list within the 2014-2015 National Ambulatory Medical Care Survey data., Results: Among 162.7 million visits in which patients were taking opioid medication(s), substance use counseling was provided in 2.4%. During visits for patients receiving opioid(s) plus GABAergic(s), substance use counseling was marginally more common (3.1% versus 2.0%, P < .0001). Substance use counseling was also more common among visits for patients taking opioid(s) with SUD (18.9% versus 1.5%, P < .0001). Among visits in which a patient was diagnosed with SUD and taking opioid(s) plus GABAergic(s), counseling was more common (23.1% versus 1.4%, P < .0001) compared to patients taking opioid(s) plus GABAergic(s) without SUD., Conclusions: Among national ambulatory care visits in the United States, substance use counseling is provided infrequently for patients taking opioids, even when significant risk factors are present. Increasing patient education may help reduce opioid-related overdose mortality., Competing Interests: Declaration of conflicting interest:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CEL serves on the Executive Committee of the University of Pennsylvania’s Center for Pharmacoepidemiology Research and Training. The Center receives unrestricted funding from Pfizer and Sanofi. CEL’s spouse is employed by a health technology company that receives funding from AbbVie, Adamas, Celgene, Lilly, Lundbeck, Novartis, and Sunovion. JRC has received previous research funding from Novartis Pharmaceuticals and the College of Psychiatric and Neurologic Pharmacists unrelated to this project. The other authors of this study have no conflicts of interest to disclose., (© The Author(s) 2020.)

Objective: The aim of this article is to update ADHD diagnosis/treatment trends by age, gender, and race. Method: National Ambulatory Medical Care Survey data were obtained for 2008-2009 to 2012-2013. Physician office visits including ADHD diagnosis and pharmacotherapy were measured per 1,000 population and per 1,000 office visits overall, and by demographic group. Logistic regression models controlled for demographics, psychiatric comorbidities, insurance type, and time period. Interactions of time, demographics, comorbidities, and insurance type were tested. Results: Diagnoses of ADHD increased by 36% in adults and 18% in youth, and diagnosis + drug by 29% in female and 10% in male youths. ADHD diagnosis was 77% less likely among Black than White adults but 24% more likely among Black than White youths in 2012-2013. Conduct disorder (CD) in youths multiplied odds of diagnosis + drug by 3.31; interaction of Black race × CD by 3.78. Conclusion: Upward trends in ADHD diagnosis and treatment have continued but vary markedly by group. Studies of undertreatment/overtreatment are needed.

Background: Reports of gabapentinoid (gabapentin and pregabalin) misuse have increased in recent years. Pharmacovigilance data from the Food and Drug Administration Adverse Event Reporting System (FAERS) provides a useful examination of adverse drug event (ADE) reporting for safety signal detection., Objective: This study was conducted to analyze epidemiological information on the nature and extent of gabapentin/pregabalin abuse utilizing the FAERS database., Methods: A query was designed utilizing SafeRx, an indexed, searchable database of FAERS data from October 2012-December 2016. All-cause and abuse-related (including abuse/misuse/dependence/overdose events) ADE reports for gabapentin and pregabalin were isolated, as well as limited demographic data. The proportional reporting ratio (PRR) was calculated to compare signal detection., Results: A total of 10,038 all-cause ADEs were reported to FAERS for gabapentin, including 576 (5.7%) abuse-related events. For pregabalin, 571 all-cause ADEs were identified, including 58 (10.2%) related to abuse. Compared to all-cause ADEs, those involved in abuse-related events were younger and more likely to be male. The PRR of pregabalin versus gabapentin abuse-related events was 1.77., Conclusion: Though not traditionally thought of as drugs of abuse, over 600 cases of gabapentinoid abuse were reported in the time frame analyzed, prompting the need for further study and regulatory investigation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Tardive dyskinesia is a potentially irreversible, debilitating, hyperkinetic movement disorder that can result from dopamine receptor antagonists. Prompt recognition and resolution of symptoms are instrumental in preventing disease irreversibility, though current treatment options have fallen short of robust, effective, and long-term symptom control. In April 2017, the Food and Drug Administration (FDA) approved 2 new vesicular monoamine transporter 2 (VMAT2) inhibitors, deutetrabenazine and valbenazine, for chorea related to Huntington's disease and tardive dyskinesia, respectively. These agents were pharmacologically modified from tetrabenazine, a VMAT2 inhibitor used off-label in the treatment of tardive dyskinesia. Despite FDA-labeled indications of deutetrabenazine and valbenazine, each agent was explored as a treatment option for those with tardive dyskinesia. In this study, the pharmacologic modifications of the 2 new VMAT2 inhibitors are described, with detailed explanation as to how these may impact clinical practice. The associated case series, observational studies, and clinical trials exploring their use in the treatment of tardive dyskinesia are reported with expert opinion on practice implication.

Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug-drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders-antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder-and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.

Co-prescription of opioid and benzodiazepine products increases the risk of overdose-related mortality four-fold due to respiratory depression. Accordingly, prevention of high-risk opioid prescribing (HROP) has become a focus over the past two decades and was the subject of a black-box warning (BBW) issued by the U.S. Food and Drug Administration (FDA) on August 31, 2016. Because older patients are at increased risk for these outcomes, we compared rates of HROP for older (aged ≥65 years) and younger (aged 18-64 years) adults using a repeated cross-sectional cohort design. Data from the National Ambulatory Medical Care Survey of U.S. office-based physician visits were accessed for 2006-2016 August. From 2006 to 2016, the opioid-prescribing rate increased by 40% among those aged 18-64 years and by 54% among those aged ≥65 years. From 2012-2013 to 2014-2016, the HROP rate, expressed as a proportion of all opioid-prescribing visits, increased to 26.6% among those aged 18-64 years but declined to 21.0% among those aged ≥65 years, primarily because of changes for patients aged ≥75 years. Prior to the FDA-issued BBW, the HROP prescribing rate trended upward for all adults, except in 2014-2016 when it began to decline among older adults., Competing Interests: The authors declare there is no conflict of interest.

Gabapentin is widely used in the United States for a number of off-label indications, often as an alternative to opioid therapy. Increasing evidence has emerged suggesting that gabapentin may not be as benign as once thought and may be associated with substance abuse in concert with opioids. With concerns for safety mounting, it is prudent to examine the efficacy of gabapentin across its many uses to understand the risk-benefit balance. Reviews on off-label indications such as migraine, fibromyalgia, mental illness, and substance dependence have found modest to no effect on relevant clinical outcomes. This high-quality evidence has often been overshadowed by uncontrolled studies and limited case reports. Furthermore, the involvement of gabapentin in questionable marketing schemes further calls its use into question. Overall, clinicians should exercise rigorous appraisal of the available evidence for a given indication, and researchers should conduct larger, higher-quality studies to better assess the efficacy of gabapentin for many of its off-label uses., Competing Interests: Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.R.C. acknowledges current and previous research funding from Novartis Pharmaceuticals and the College of Psychiatric and Neurologic Pharmacists, unrelated to this work. The other authors declare that there are no conflicts of interest.

Objective: To conduct a proof-of-concept study comparing Lorenz-curve analysis (LCA) with power-law (exponential function) analysis (PLA), by applying segmented regression modeling to 1-year prescription claims data for three medications-alprazolam, opioids, and gabapentin-to predict abuse and/or diversion using power-law zone (PLZ) classification., Results: In 1-year baseline observation, patients classified into the top PLZ groups (PLGs) were demographically and diagnostically similar to those in Lorenz-1 (top 1% of utilizers) and Lorenz-25 (top 25%). For prediction of follow-up (6-month post-baseline) Lorenz-1 use of alprazolam and opioids (i.e., potential abuse/diversion), PLA had somewhat lower sensitivity compared with LCA (83.5-95.4% vs. 99.5-99.9%, respectively) but better specificity (98.2-98.8% vs. 75.5%) and much better positive predictive value (PPV; 34.5-45.3% vs. 4.0-4.6%). Of top-PLG alprazolam- and opioid-treated patients, respectively, 20.7 and 9.9% developed incident (new) Lorenz-1 in followup, compared with < 3% of Lorenz-25 patients. For gabapentin, neither PLA nor LCA predicted incident Lorenz-1 (PPV = 0.0-1.4%). For all three medications, PLA sensitivity for follow-up hospitalization was < 5%, but specificity was better for PLA (97.3-99.2%) than for LCA (74.3-75.4%). PLA better identified patients at risk of future controlled substance abuse/diversion than did LCA, but the technique needs refinement before widespread use.

Context: The alarming increase in opioid-related fatalities has placed the United States in the midst of an opioid epidemic. In an effort to reduce opioid-related fatalities, each Veterans Affairs (VA) hospital is responsible for development of an OEND (Overdose Education and Naloxone Distribution) program to enhance naloxone distribution., Objective: To assess attitudes, knowledge, comfort level, and fear of consequences at the prescriber level related to the OEND program at VA Connecticut Healthcare System (VACHS)., Design: Anonymous surveys were administered to VACHS prescribers to assess attitude, knowledge, comfort level, and fear of consequences using a 5-point Likert scale., Setting: VACHS., Participants: VACHS prescribers (primary care physicians/internists, psychiatrists, physician assistants/advanced practice registered nurses, pharmacists) in primary care/medicine, mental health, and substance use disorder (SUD)., Methods: Differences across 4 domains were analyzed using analysis of variance testing, and pairwise post hoc analysis was conducted using Tukey's HSD for all significant findings. Regression modeling was conducted to evaluate correlations between each group and survey responses., Main Outcome: Identify differences and potential barriers to program implementation across professions and practice specialty., Results: While primary care/medicine, mental health, and SUD prescribers had positive attitudes toward dispensing naloxone, SUD clinicians reported being more comfortable, more knowledgeable, and less fearful of consequences. In general, psychiatrists reported to be more knowledgeable and comfortable prescribing naloxone. In addition, prescribers who received naloxone training reported themselves to be more comfortable, more knowledgeable, and less fearful of the consequences of dispensing naloxone., Conclusions: Results indicate that barriers to OEND implementation continue to exist, and not all clinicians or practice specialties at VACHS are comfortable with dispensing naloxone. A targeted approach to training health care clinicians may lead to increased acceptance of naloxone dispensing. Additional research is needed to elicit the best method of improved acceptance of naloxone to expand naloxone access.

Introduction: Past trials of buprenorphine (BUP) in the treatment of major depressive disorder (MDD) have displayed favorable results, although its clinical utility was limited by the risk of abuse or physical dependence. By combining BUP with samidorphan (SAM), the euphoric high is negated by an opposing mechanism, which theoretically reduces addictive-like properties while allowing the antidepressant properties to remain. As such, the objective of this article is to analyze the results of BUP/SAM premarketing clinical trials as adjunctive treatment for treatment-resistant MDD., Methods: A comprehensive PubMed/MEDLINE search was conducted through November 9, 2017, using the following search terms: depression, samidorphan, buprenorphine, ALKS-5461. Additional data were obtained from Clinicaltrials.gov and resources included in the present study. All English-language clinical trials evaluating the combination of BUP/SAM in the treatment of MDD were included., Results: A few premarketing studies have evaluated the efficacy and safety of BUP/SAM combination as adjunctive treatment in patients with treatment-resistant MDD. The FORWARD-1 through FORWARD-5 trials concluded (1) the most effective dosing ratio of BUP/SAM to reduce abuse potential was 1:1; (2) statistically significant changes in scores from baseline on the Montgomery-Asberg Depression Rating Scale were noted for the 2 mg/2 mg dose compared with placebo; and (3) the most commonly reported adverse effects were nausea, dizziness, and fatigue., Discussion: Buprenorphine/samidorphan has shown favorable results for efficacy and tolerability in premarketing studies evaluating its use as adjunctive therapy for treatment-resistant MDD. Its novel mechanism targeting the opioid pathway may serve as a promising antidepressant devoid of abuse potential., Competing Interests: Disclosures: The authors have nothing to disclose.

Introduction: Over the past decade, increased prescription supply has facilitated an epidemic of nonmedical use of controlled substances, including predominantly opioids, as well as benzodiazepines, z-hypnotics, and stimulants. Areas covered: More recently, misuse of noncontrolled prescriptions, such as gabapentin, has been detected. Gabapentin misuse has been associated with drug-related harm and increased healthcare service utilization in a few studies, including a recent large-sample analysis of commercially insured enrollees in the United States (U.S.) Responding to this emerging base of evidence, a small number of U.S. states have acted to prevent or detect gabapentin misuse by requiring the inclusion of gabapentin utilization in reporting to local Prescription Drug Monitoring Programs (PDMPs) and/or imposing other restrictions on gabapentin prescribing (e.g., classification as a controlled substance, quantity limits). These efforts may result in unintentional harm by (1) encouraging 'doctor shopping' across state lines to seek lenient regulatory policies and (2) placing the burden for mitigating misuse on individual practitioners. Expert opinion: We call for a unified national approach, comprising federal regulation and enhanced PDMP reporting to address gabapentin misuse, while laying the groundwork for management of new medications of abuse that the healthcare industry may encounter in the future.

Objective: Research suggests the medical consequences of gabapentin overuse depend on whether gabapentin is abused alone or with opioids to potentiate an opioid "high." The objective of this study was to assess predictors of gabapentin overuse with or without concomitant opioids., Methods: Data were obtained from the Truven Health MarketScan ® Commercial Claims and Encounters database for 2013 through 2015. Eligibility criteria were gabapentin utilization, with or without opioids, for 120 days or longer throughout a 12-month observation period. Cohort identification was based on patterns of overuse exceeding thresholds of 3600 mg of gabapentin and/or 50 morphine-mg equivalents of opioids; sustained overuse was defined as three or more quarters exceeding threshold. Diagnostic predictors were measured in the 6 months pretreatment in inpatient (IP) or emergency department (ED) settings. Indications were measured in IP, ED, or ambulatory settings. Logistic regression analyses adjusted for age, sex, indication, use of benzodiazepine or z-hypnotics (i.e., zaleplon, zolpidem, eszopiclone) during gabapentin treatment, pretreatment ED/IP use, and pretreatment diagnoses of anxiety or depression., Results: Criteria for sustained overuse were met by 2.0% of 44,148 patients treated with gabapentin without opioids and by 11.7% of 15,335 patients treated with concomitant gabapentin-opioid. The top three predictors of sustained overuse for gabapentin-only patients were insomnia (7.0%), euphoria (4.5%), and bipolar disorder (4.5%), and were detoxification (35.6%), altered mental status (26.3%), and addiction (21.6%) for gabapentin-opioid patients. In adjusted analyses, concomitant opioid use multiplied the odds of sustained misuse by 6.32 (95% confidence interval [CI] = 5.80-6.89) and the interaction of addiction with opioid use by 1.88 (95% CI = 1.32-2.66). Among gabapentin-only patients, sustained misuse was predicted by a history of anxiety (odds ratio = 1.56, 95% CI = 1.02-2.38) but not by a history of addiction., Conclusions: The likelihood of gabapentin overuse alone is low but significantly increases with concomitant opioid use, especially when coupled with a history of addiction. History of addiction does not appear to increase risk of gabapentin misuse among those with gabapentin alone., (© 2018 Pharmacotherapy Publications, Inc.)

Background: Among US adults, utilization of pharmacotherapy for attention-deficit hyperactivity disorder (ADHD) has increased more than ninefold since 1995-1996. Potential contraindications to ADHD pharmacotherapy include serious cardiovascular disease (CVD) and, for stimulants, addictions and bipolar disorder (BPD)., Objective: To assess the prevalence of potential contraindications among adults treated with ADHD pharmacotherapy., Methods: A retrospective cohort analysis was performed using the Truven Health MarketScan ® database. Subjects filled ≥ 1 prescription for atomoxetine or ≥ 1 stimulant in 2014-2015, were aged 18-64 years, commercially insured throughout observation, and diagnosed with ADHD on two or more medical claims. Diagnoses and medical procedures were measured in the 12 months prior to pharmacotherapy initiation. Metrics included serious CVD (cardiomegaly, cardiomyopathy, cerebrovascular occlusion, congestive heart failure, myocardial infarction, pacemaker, or valvular disorder) and any CVD (serious CVD, other atherosclerotic CVD, arrhythmia, congenital heart anomaly, or hypertensive heart disease). Rates of substance addiction or abuse were measured in a range to address nonspecific diagnostic coding., Results: Only 2.0% of treated adults (n = 91,588) had one or more diagnosis indicating serious CVD. CVD prevalence increased monotonically with age. Of patients aged 55-64 years (n = 5,237), 7.2% had serious CVD; 15.9% had any CVD; and 1.9% had been hospitalized with one or more CVD. Of patients treated with stimulants (n = 87,167), 11.3-18.5% were diagnosed with addiction/abuse and 4.1% with BPD., Conclusions: CVD prevalence is generally low among adults using ADHD medication but increases with age. Although difficult to estimate precisely, the rate of addiction/abuse among stimulant-treated patients appears unexpectedly high. Further research should assess cardiovascular events and other potential harms associated with contraindicated use in high-risk adults.

Introduction: Overuse of gabapentin and/or opioids occurs in a small percentage of patients at > 3-fold labeled dosages. Gabapentin may potentiate opioid effects., Objective: The aim was to assess patient harm, defined as use of inpatient hospital (IPH) or emergency department (ED) services, associated with overuse of gabapentin with or without concomitant overuse of opioids., Data Source: Data were sourced from the Truven Health MarketScan ® Commercial Claims and Encounters database, for the years 2013-2015., Eligibility Criteria: The eligibility criteria were two or more claims (billed encounters) and ≥120 days of treatment with gabapentin and/or opioids., Methods: Cohort identification was based on daily-dosage thresholds of 50 morphine-milligram equivalents and 3600 mg of gabapentin in a 12-month follow-up: (1) no overuse; (2) mild overuse (two or more claims or two or fewer calendar quarters over threshold); and (3) sustained overuse (three or more over-threshold calendar quarters). IPH and ED use were measured for 6 months after the first overuse date (cohorts 2 and 3) or a randomly assigned date (cohort 1). Logistic regression analyses controlled for pre-treatment IPH/ED utilization, indication, addiction diagnosis, concomitant sedative/hypnotic use, and demographics., Results: All-cause and drug-related IPH/ED utilization increased monotonically with degree of overuse, particularly of more than one medication. Sustained overuse of gabapentin multiplied odds of all-cause IPH by 1.366 [95% confidence interval (CI) 1.055-1.769], drug-related IPH by 1.440 (95% CI 1.010-2.053), and IPH/ED for altered mental status (e.g., euphoria, anxiety) by 1.864 (95% CI 1.324-2.624). Sustained overuse of both medications quadrupled odds of all-cause IPH, drug-related IPH, and IPH/ED for altered mental status or respiratory depression., Conclusion: Despite modest effects of gabapentin overuse alone, overuse of gabapentin with opioids may increase risk of harm and health-service utilization, supporting calls to make gabapentin a controlled substance in the USA.

Background: Despite international calls to make gabapentin a controlled substance, studies of gabapentin use/abuse patterns are limited to small/high-risk samples and adverse event reports., Objective: The aim of this study was to conduct a systematic assessment of the abuse potential/prevalence of gabapentin in a large sample., Data Source: Truven Health MarketScan ® Commercial Claims and Encounters database, years 2013-2015., Eligibility Criteria: Patients with two or more claims for one or more abusable drugs and ≥12 months' continuous enrollment were sampled for Lorenz curve analysis. Prevalence analysis was limited to those with ≥120 days of therapy., Methods: Abuse potential was measured as Lorenz-1 (consumption of drug supply by top 1% of users) of ≥15%. Dose thresholds were morphine milligram equivalent (MME) standards for opioids, and maximum labeled doses in milligrams (mg) for other drugs., Results: Lorenz-1 values were 37% opioids, 19% gabapentin, 15% pregabalin, 14% alprazolam, and 13% zolpidem. The top 1% gabapentin users filled prescriptions for a mean (median) 11,274 (9534) mg/day, more than three times the recommended maximum (3600 mg). Of these, one-quarter used or diverted ≥12,822 mg/day. The top 1% opioid and pregabalin users filled prescriptions for a mean (median) 180 (127) MMEs and 2474 (2219) mg/day, respectively. Of patients using opioids + gabapentin simultaneously, 24% had three or more claims exceeding the dose threshold within 12 months., Limitations: Established threshold criteria for gabapentinoid abuse are uncertain. Indications for gabapentinoid use (e.g. hot flashes, restless legs syndrome) were not measured., Conclusion: Gabapentin use patterns are similar to those of other abusable medications. High daily doses pose safety and/or diversion concerns, and investigation of the medical consequences of gabapentin abuse is needed.

A pilot program was developed to distribute naloxone kits, educate patients on opioid use risks, and reduce the number of overdose deaths., Competing Interests: Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.