Alyssa M. Peckham

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.

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.

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.

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.

Background A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since grown substantially. Objective Update previous SR and describe new insights regarding gabapentinoid abuse. Methods A SR of PubMed was conducted to identify studies published from 7/29/2016–8/31/2020. Four searches were performed using the following terms: “gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid” AND one of the following substance misuse/abuse-related terms: “substance-related disorders [MeSH]”, “overdose”, “abuse”, or “misuse”. Clinicaltrials.gov and the Cochrane Library database were searched to identify ongoing studies or similar SRs. Reference lists of included studies were reviewed to identify additional literature. All studies with novel data related to pregabalin and/or gabapentin abuse, misuse, or overdose conducted during the study period were included. Articles not written in English, review articles, and animal studies were excluded. Results Fifty-five studies were included (29 [52.7%] from North America, 17 [30.9%] Europe, 6 [10.9%] Asia, and 3 [5.5%] Australia). Forty-six observational studies and 10 case reports/series were included (one manuscript included both). Twenty (36.4%) studied gabapentin only, 18 (32.7%) pregabalin only, and 17 (30.9%) both pregabalin/gabapentin. These studies corroborate findings from the previous SR that gabapentinoids are increasingly abused or misused to self-medicate, that gabapentinoids can produce desirable effects alone but are often used concomitantly with other drugs, and that opioid use disorder is the greatest risk factor for gabapentinoid abuse. While the original SR identified the largest studies having been published in Europe, this review identified several more generalisable US studies that have subsequently been conducted. The most concerning finding was increased evidence of associated patient harm, including increased hospital utilisation and opioid-related overdose mortality risk. Conclusion Evidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse.