Michael A. Yokell

Buprenorphine and Buprenorphine/Naloxone Diversion, Misuse, and Illicit Use: An International Review

The diversion, misuse, and non-medically supervised use of buprenorphine and buprenorphine/naloxone by opioid users are reviewed. Buprenorphine and buprenorphine/naloxone are used globally as opioid analgesics and in the treatment of opioid dependency. Diversion of buprenorphine and buprenorphine/naloxone represents a complex medical and social issue, and has been widely documented in various geographical regions throughout the world. We first discuss the clinical properties of buprenorphine and its abuse potential. Second, we discuss its diversion and illicit use on an international level, as well as motivations for those activities. Third, we examine the medical risks and benefits of buprenorphines non-medically supervised use and misuse. These risks and benefits include the effect of buprenorphines use on HIV risk and the risk of its concomitant use with other medications and drugs of abuse. Finally, we discuss the implications of diversion, misuse, and non-medically supervised use (including potential measures to address issues of diversion); and potential areas for further research.

Illicit use of buprenorphine/naloxone among injecting and noninjecting opioid users.

Objectives:We examined the use, procurement, and motivations for the use of diverted buprenorphine/naloxone among injecting and noninjecting opioid users in an urban area. Methods:A survey was self-administered among 51 injecting opioid users and 49 noninjecting opioid users in Providence, RI. Participants were recruited from a fixed-site syringe exchange program and a community outreach site between August and November 2009. Results:A majority (76%) of participants reported having obtained buprenorphine/naloxone illicitly, with 41% having done so in the previous month. More injection drug users (IDUs) than non-IDUs reported the use of diverted buprenorphine/naloxone (86% vs 65%, P = 0.01). The majority of participants who had used buprenorphine/naloxone reported doing so to treat opioid withdrawal symptoms (74%) or to stop using other opioids (66%) or because they could not afford drug treatment (64%). More IDUs than non-IDUs reported using diverted buprenorphine/naloxone for these reasons. Significantly more non-IDUs than IDUs reported ever using buprenorphine/naloxone to “get high” (69% vs 32%, P < 0.01). The majority of respondents, both IDUs and non-IDUs, were interested in receiving treatment for opioid dependence, with greater reported interest in buprenorphine/naloxone than in methadone. Common reasons given for not being currently enrolled in a buprenorphine/naloxone program included cost and unavailability of prescribing physicians. Conclusions:The use of diverted buprenorphine/naloxone was common in our sample. However, many opioid users, particularly IDUs, were using diverted buprenorphine/naloxone for reasons consistent with its therapeutic purpose, such as alleviating opioid withdrawal symptoms and reducing the use of other opioids. These findings highlight the need to explore the full impact of buprenorphine/naloxone diversion and improve the accessibility of buprenorphine/naloxone through licensed treatment providers.

HIV infection and risk of overdose: a systematic review and meta-analysis

Drug overdose is a common cause of non-AIDS death among people with HIV and the leading cause of death for people who inject drugs. People with HIV are often exposed to opioid medications during their HIV care experience; others may continue to use illicit opioids despite their disease status. In either situation, there may be a heightened risk for nonfatal or fatal overdose. The potential mechanisms for this elevated risk remain controversial. We systematically reviewed the literature on the HIV–overdose association, meta-analyzed results, and investigated sources of heterogeneity, including study characteristics related to hypothesize biological, behavioral, and structural mechanisms of the association. Forty-six studies were reviewed, 24 of which measured HIV status serologically and provided data quantifying an association. Meta-analysis results showed that HIV seropositivity was associated with an increased risk of overdose mortality (pooled risk ratio 1.74, 95% confidence interval 1.45, 2.09), although the effect was heterogeneous (Q = 80.3, P < 0.01, I2 = 71%). The wide variability in study designs and aims limited our ability to detect potentially important sources of heterogeneity. Causal mechanisms considered in the literature focused primarily on biological and behavioral factors, although evidence suggests structural or environmental factors may help explain the greater risk of overdose among HIV-infected drug users. Gaps in the literature for future research and prevention efforts as well as recommendations that follow from these findings are discussed.

The Feasibility of Pharmacy-Based Naloxone Distribution Interventions: A Qualitative Study With Injection Drug Users and Pharmacy Staff in Rhode Island

This study analyzed qualitative data from a Rapid Policy Assessment and Response project to assess the feasibility of a potential pharmacy-based naloxone intervention to reduce opioid overdose mortality among injection drug users (IDUs). We conducted in-depth, semistructured interviews with 21 IDUs and 21 pharmacy staff (pharmacists and technicians). Although most participants supported the idea of a pharmacy-based naloxone intervention, several barriers were identified, including misinformation about naloxone, interpersonal relationships between IDUs and pharmacy staff, and costs of such an intervention. Implications for future pharmacy-based overdose prevention interventions for IDUs, including pharmacy-based naloxone distribution, are considered. The studys limitations are noted.

Forced withdrawal from methadone maintenance therapy in criminal justice settings: A critical treatment barrier in the United States

The World Health Organization classifies methadone as an essential medicine, yet methadone maintenance therapy remains widely unavailable in criminal justice settings throughout the United States. Methadone maintenance therapy is often terminated at the time of incarceration, with inmates forced to withdraw from this evidence-based therapy. We assessed whether these forced withdrawal policies deter opioid-dependent individuals in the community from engaging methadone maintenance therapy in two states that routinely force inmates to withdraw from methadone (N = 205). Nearly half of all participants reported that concern regarding forced methadone withdrawal during incarceration deterred them engaging methadone maintenance therapy in the community. Participants in the state where more severe methadone withdrawal procedures are used during incarceration were more likely to report concern regarding forced withdrawal as a treatment deterrent. Methadone withdrawal policies in the criminal justice system may be a broader treatment deterrent for opioid-dependent individuals than previously realized. Redressing this treatment barrier is both a health and human rights imperative.

Prescription Drug Monitoring Programs

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Reported Experiences During Syringe Purchases in Providence, Rhode Island: Implications for HIV Prevention

Use of injection drugs remains a public health concern, with injection drug users (IDUs) experiencing an elevated risk of morbidity and mortality. While the sale of non-prescription syringes in pharmacies is legal in most states, some pharmacists choose not to sell non-prescription syringes, or opt to sell syringes in quantities too large for purchase by many IDUs. Thus, we sought to understand the interpersonal experience of syringe sale/ purchase, the implications of policies regarding syringe sales, and pharmacy staff and IDU (mis)perceptions about one another. We conducted in-depth, semi-structured interviews with 21 IDUs and 21 pharmacy staff (pharmacists and pharmacy technicians). Some important emergent themes were that individual experiences influenced overall perceptions, that IDUs and pharmacy staff differentiated between IDUs and other customers, and that some pharmacy staff demonstrated an understanding of the public health importance of accessible sterile syringes. Implications for future pharmacy-based interventions for IDUs are considered.

Adverse event associated with a change in nonprescription syringe sale policy

OBJECTIVE To report and describe the possible correlation of a change in syringe sale policy at a community pharmacy with an adverse clinical outcome. SETTING Providence, RI, in summer 2009. PATIENT DESCRIPTION 27-year-old white woman with a long-standing history of chronic relapsing opiate addiction and human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection. CASE SUMMARY The patient presented to the hospital emergency department with 5 days of severe diffuse pain, swelling in her hands and feet, and several days of rigors with fevers, sweats, and chills. She was diagnosed with sepsis resulting from a disseminated methicillin-resistant Staphylococcus aureus (MRSA) infection. The patient was treated with intravenous antibiotics, neurosurgical drainage of an epidural abscess, intensive care unit care for 1 week, and acute hospitalization for 8 weeks. MAIN OUTCOME MEASURES Not applicable. RESULTS A few weeks before the patient was hospitalized, pharmacists at her local neighborhood pharmacy decided to stop selling syringes in packages of 10. Instead, syringes were sold at a minimum quantity of 100. The patient did not know where to obtain sterile syringes and began reusing syringes. CONCLUSION The patient introduced pathogenic bacteria from her skin into her bloodstream through unsafe injection practices. The change in syringe sale policy at her local pharmacy likely inadvertently contributed to this severe and life-threatening situation. Consideration of the implications of syringe sale policy must include an understanding of the barriers that influence individual pharmacists decisions regarding particular store policies that affect over-the-counter syringe sales. Legalized sale of nonprescription syringes in community pharmacies alone is not enough to curb the epidemic of unsafe injection practices in the United States. All medical risks that are inherent in the use of unsafe syringes, including blood-borne viral pathogens (e.g., HIV, HCV) and bacterial infections (e.g., MRSA), should be considered.

Characteristics of United States emergency departments that routinely perform alcohol risk screening and counseling for patients presenting with drinking-related complaints.

Introduction Emergency department (ED) screening and counseling for alcohol misuse have been shown to reduce at-risk drinking. However, barriers to more widespread adoption of this service remain unclear. Methods We performed a secondary analysis of a nationwide survey of 277 EDs to determine the proportion of EDs that routinely perform alcohol screening and counseling among patients presenting with alcohol-related complaints and to identify potential institutional barriers and facilitators to routine screening and counseling. The survey was randomly mailed to 350 EDs sampled from the 2007 National Emergency Department Inventory (NEDI), with 80% of ED medical directors responding after receiving the mailing or follow-up fax/email. The survey asked about a variety of preventive services and ED directors’ opinions regarding perceived barriers to offering preventive services in their EDs. Results Overall, only 27% of all EDs and 22% of Level I/II trauma center EDs reported routinely screening and counseling patients presenting with drinking-related complaints. Rates of routine screening and counseling were similar across geographic areas, crowding status, and urban-rural status. EDs that performed routine screening and counseling often offered other preventive services, such as tobacco cessation (P<0.01) and primary care linkage (P=0.01). EDs with directors who expressed concern about increased financial costs to the ED, inadequate follow-up, and diversion of nurse/physician time all had lower rates of screening and counseling and also more frequently reported lacking the perceived capacity to perform routine counseling and screening. Among EDs that did not routinely perform alcohol screening and counseling, more crowded than non-crowded (P<0.01) and more metro than rural (P<0.01) EDs reported lacking the capacity to perform routine screening and counseling. The capacity to perform routine screening also decreased as ED visit volume increased (P=0.04). Conclusion To increase routine alcohol screening and counseling for patients presenting with alcohol-related complaints, ED directors’ perceived barriers related to an ED’s capacity to perform screening, such as limited financial and staff resources, should be addressed, as should directors’ concerns regarding the implementation of preventive health services in EDs. Uniform reimbursement methods should be used to increase ED compensation for performing this important and effective service.

National Variation in Opioid Prescribing and Risk of Prolonged Use for Opioid-Naive Patients Treated in the Emergency Department for Ankle Sprains

Study objective To inform opioid stewardship efforts, we describe the variation in emergency department (ED) opioid prescribing for a common minor injury, ankle sprain, and determine the association between initial opioid prescription intensity and transition to prolonged opioid use. Methods We analyzed 2011 to 2015 US private insurance claims (Optum Clinformatics DataMart) for ED‐treated ankle sprains among opioid‐naive patients older than 18 years. We determined the patient‐ and state‐level variation in the opioid prescription rate and characteristics, and the risk‐adjusted association between total morphine milligram equivalents (MMEs) of the prescription and transition to prolonged use (filling 4 or more opioid prescriptions 30 to 180 days after the index visit). Results A total of 30,832 patients met inclusion criteria. Of these patients, 25.1% received an opioid prescription with a median total MME of 100 (interquartile range 75 to 113), tablet quantity of 15 (interquartile range 12 to 20), and days supplied of 3 (interquartile range 2 to 4). State‐level prescribing rates ranged from 2.8% in North Dakota to 40.0% in Arkansas. Among patients who received a total MME of greater than 225 (equivalent to >30 tabs of oxycodone 5 mg), the adjusted rate of prolonged opioid use was 4.9% (95% CI 1.8% to 8.1%) compared with 1.1% (95% CI 0.7% to 1.5%) among those who received at total MME of 75 and 0.5% (95% CI 0.4% to 0.6%) among those who did not fill an opioid prescription. Conclusion Opioid prescribing for ED patients treated for ankle sprains is common and highly variable. Although infrequent in this population, prescriptions greater than 225 MME were associated with higher rates of prolonged opioid use. This is concerning because these prescriptions could still fall within 5‐ or 7‐day supply limit policies aimed at promoting safer opioid prescribing.