Matthew Stephen Ellis

Objectives: Persons with opioid use disorder (OUD) are at elevated risk for engaging in the nonmedical use (NMU) of gabapentin. Despite the increased risk of respiratory depression from concomitant use of gabapentin and opioids, gabapentin is often prescribed in OUD treatment settings. This study examines the relationship between gabapentin prescribing histories and the initiation, patterns, and motivations of gabapentin NMU. Methods: Twenty-one OUD treatment centers recruited 181 adults in 23 states reporting either past 12-month gabapentin NMU (n=150) or use only as prescribed (N=31). Cross-sectional interviews assessed demographics, substance use history/patterns, and gabapentin prescribing histories. Results: Most NMU participants had a prior prescription for gabapentin (72.1%), with 45.3% having a current prescription; 27.7% had no prescription history. Diversion of gabapentin was highly prevalent for obtaining (sharing/trading=50.0%; dealer/street purchase=44.0%) and distributing gabapentin (45.3% diverted to others). Those with gabapentin NMU had higher gabapentin, but not opioid, craving scores compared with those with use as prescribed (3.8 vs. 2.2, P <0.001). Both therapeutic (84.7%) and recreational motivations (74.7%) were widely endorsed and involved high average doses (2061 mg and 2394 mg, respectively). Conclusions: Pathways to initiating gabapentin NMU among individuals with OUD are varied and include health care and nonhealth care channels. High rates of both recreational and therapeutic motivations may suggest the utility of gabapentin in potentiating opioid effects and mitigating gaps in unmet health care needs. Despite risks of concomitant use, many individuals had current prescriptions for gabapentin, highlighting the importance of screening, monitoring and risk counseling when considering gabapentin prescriptions in OUD populations.

Importance: Gabapentin prescriptions have drastically increased in the US due to off-label prescribing in settings such as opioid use disorder (OUD) treatment to manage a range of comorbid conditions and withdrawal symptoms, despite a lack of evidence.Objective: To assess the purpose and associated risks of off-label gabapentin use in OUD treatment.Design, Setting, and Participants: This retrospective recurrent-event case-control study with a crossover design used administrative claims data from MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Individuals aged 12 to 64 years with an OUD diagnosis and filling buprenorphine prescriptions were included in the primary analysis conducted from July 1, 2022, through June 1, 2023. Unit of observation was the person-day.Exposures: Days covered by filled gabapentin prescriptions.Main Outcomes and Measures: Primary outcomes were receipt of gabapentin in the 90 days after initiation of buprenorphine treatment and drug-related poisoning. Drug-related poisonings were defined using codes from International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.Results: A total of 109 407 patients were included in the analysis (mean [SD] age, 34.0 [11.2] years; 60 112 [54.9%] male). Among the 29 967 patients with Medicaid coverage, 299 (1.0%) were Hispanic, 1330 (4.4%) were non-Hispanic Black, 23 112 (77.1%) were non-Hispanic White, and 3399 (11.3%) were other. Gabapentin was significantly less likely to be prescribed to Black or Hispanic patients, and more likely to be prescribed to female patients, those with co-occurring substance use or mood disorders, and those with comorbid physical conditions such as neuropathic pain. Nearly one-third of persons who received gabapentin (4336 [31.1%]) had at least 1 drug-related poisoning after initiating buprenorphine treatment, compared with 13 856 (14.5%) among persons who did not receive gabapentin. Adjusted analyses showed that days of gabapentin use were not associated with hospitalization for drug-related poisoning (odds ratio, 0.98 [95% CI, 0.85-1.13]). Drug-related poisoning risks did not vary based on dosage.Conclusions and Relevance: Gabapentin is prescribed in the context of a myriad of comorbid conditions. Even though persons receiving gabapentin are more likely to have admissions for drug-related poisoning, these data suggest that gabapentin is not associated with an increased risk of drug-related poisoning alongside buprenorphine in adjusted analyses. More data on the safety profile of gabapentin in OUD settings are needed.

Background and Objective While the current landscape of opioid use disorder (OUD) is complicated by the increase in use of non-prescription opioids, prescription opioids continue to be frequently used in non-medical ways. In response to this abuse, pharmaceutical companies have developed abuse deterrent formulations (ADFs) for extended-release (ER) opioids. To test the effectiveness of Xtampza ER ADF (oxycodone myristate) at reducing tampering, its rate of tampering in a treatment-center population was compared to immediate release (IR) single entity (SE) oxycodone, other ER oxycodone opioids, and ER oxymorphone. Methods Data were collected between the third quarter of 2018 and the third quarter of 2021 from individuals entering nationally distributed opioid treatment programs. To determine odds of tampering with Xtampza ER compared to each comparator, a logistic model was fit with a random intercept allowing for multiple drugs in each subject. Within-subject correlation was assumed to have a compound symmetric relationship. Results Overlap among the categories of drug tampering was high. Logistic regression analyses found that oxycodone myristate had lower odds of tampering when compared to both IR SE oxycodone (OR = 0.23 [95% CI 0.11, 0.50], p = 0.0002) and ER oxymorphone (OR = 0.30 [95% CI 0.14, 0.67], p = 0.0038). Oxycodone myristate was not significantly different from other ER oxycodone opioids (OR = 0.5 [95% CI 0.24, 1.03], p = 0.0612). These findings did not change when the estimates were adjusted for age and sex. Conclusions Drugs employing ADF technology may reduce the likelihood of tampering when compared to non-ADF formulations in a treatment-center population, which represents an opportunity for intervention in OUD among those still requiring pain management.

Editorial: Broadening the scope of addiction medicine: Integrating co-morbid conditions, polysubstance use, and patient experiences into substance use treatment

Objectives: Efforts to improve low naloxone uptake to mitigate the current opioid crisis have included coprescribing naloxone with opioid medications and, more recently, expansion through over-the-counter availability, the latter of which necessitates self-identification of overdose risk by consumers. This study sought to understand perceptions of opioid overdose risk and naloxone among distinct opioid populations at elevated risk for overdose. Methods: A cross-sectional, online survey was provided to 2 opioid populations in June 2020. First, chronic pain opioid managed (CPOM; n = 190) individuals currently treated with an opioid prescription (either >50 daily morphine milligram equivalents [73.2%] or benzodiazepine co-use [52.6%]), restricted by confounders. Second, individuals with a history of opioid use disorder (OUD; n = 152) previously participating in a national opioid surveillance study of new entrants to substance use treatment centers. Results: Risk perceptions significantly differed, with 60.0% (CPOM) versus 28.9% (OUD) reporting that they were “not at all concerned about overdosing,” and 62.1% (CPOM) versus 19.1% (OUD) perceiving themselves as having “no risk” of overdose. Perceived need for naloxone was lower among CPOM versus OUD patients (48.3% and 71.8%, respectively), whereas 22.6% and 35.0%, respectively, indicated any likelihood of obtaining naloxone in the future. Conclusions: Results suggest that a significant proportion of both samples lacked the ability to self-identify their risk of overdose and self-select themselves as needing naloxone, with gaps being more prominent in the CPOM sample. A multi-intervention framework that addresses distinct pathways of behavioral change between unique opioid populations should be considered in conversations surrounding potential transitions to over-the-counter naloxone.