Buprenorphine for Opioid Use Disorder Lowers Overdose Risk in Commercially Insured Individuals

“Medications for opioid use disorder saves lives.” That’s the title and conclusion of a recent report by the National Academies of Sciences, Engineering and Medicine, based on a review of the scientific evidence. In a new study in Drug and Alcohol Dependence, CHERISH investigators Jake Morgan, Bruce Schackman and Benjamin Linas add to this evidence base by examining the real-world effectiveness of medications in preventing overdoses once treatment for opioid use disorder has begun.

 Using a database of commercially insured individuals, CHERISH investigators examined overdose risk on and off treatment with three federally approved medications for opioid use disorders–buprenorphine, extended-release injectable naltrexone, and oral naltrexone. (Methadone was excluded because it is not reliably reported in commercial claims.) From 2010-2016, they identified nearly 47,000 individuals diagnosed with an opioid use disorder and prescribed medication with an average follow up of 1.5 years per person. During that time, 1,805 individuals experienced 2,755 opioid-related overdoses (both fatal and non-fatal) as indicated by ICD-9 and ICD-10 inpatient and outpatient codes. The authors used pharmacy claims to determine whether an individual was on or off treatment in a given week.

Most overdoses (2,020) occurred while individuals were not on treatment, resulting in a rate of 4.98 overdoses per 100 person years (PY). Individuals currently on buprenorphine experienced fewer overdoses (2.08 overdoses/ 100 PY) than those on injectable naltrexone (3.85 overdoses/ 100 PY) or oral naltrexone (6.18 overdoses/ 100 PY).  After controlling for other factors such as age, sex, region of residence, insurance coverage, polypharmacy prescriptions, and visits to a treatment facility, individuals receiving buprenorphine were 60% less likely to overdose in a given week than individuals not on treatment. The overdose risk for those on naltrexone was not significantly different from those not on treatment.

To assess the risk of a “rebound” overdose after treatment was discontinued, CHERISH investigators looked at overdoses within a four-week window after discontinuation. They did not find a higher risk of overdose within four weeks after discontinuation of either buprenorphine or naltrexone. The relatively small sample of individuals on oral and injectable naltrexone made estimating the associations between overdose and naltrexone treatment and discontinuation challenging, but the lack of clear evidence of a protective effect of naltrexone is useful information for patients and prescribers.

The authors found that risk of overdose was associated with multiple prescribed drugs and a concurrent diagnosis for another substance use disorder such as alcohol, cannabis, cocaine and sedatives. They also found geographic variation in overdose risk, with patients in the Northeast and Midwest experiencing a higher risk of overdose. Being a child or dependent of a primary beneficiary was also associated with a higher risk of overdose, after controlling for age, and suggests there may be a group of emerging adults at high risk who will age out of parental insurance coverage.

The findings suggest that buprenorphine reduces overdose risk and supports the expansion of medication treatment for opioid use disorder. In 2017, about 47,000 people died from opioid-related overdoses. Less than 20% of those with an opioid use disorder receive treatment, and even fewer receive medication treatment. Increased access and use of evidence-based medications is critical to addressing the opioid overdose epidemic. Further research is needed to improve our understanding of the risks and benefits unique to each treatment in order to better tailor treatment to individual patient needs.

This post also appeared on the University of Pennsylvania Leonard Davis Institute Health Police$ense blog.

Naloxone Sales Likely to Increase after Switch to Over-the-Counter Status

Naloxone is an opioid antagonist rescue medication that reverses the effects of an opioid overdose, and thus a critical tool to prevent fatal opioid overdoses. CHERISH Investigators Drs. Sean Murphy, Jake Morgan, and Bruce Schackman, and CHERISH staff member Philip Jeng, MS predicted pharmacy sales following conversion of naloxone to over-the-counter (OTC) in a new study published in Health Services Research.

The Center for Disease Control and Prevention reported 47,600 opioid-related overdose deaths in 2017. In an effort to increase access to life saving naloxone many states and jurisdictions have passed naloxone standing order laws that allow pharmacists to dispense naloxone without a prescription. Increased availability of naloxone has been bolstered by public figures such as the US Surgeon General. To further increase access to naloxone, the Food and Drug Administration announced unprecedented new efforts to support development of OTC naloxone products. According to Dr. Murphy “although we would expect a conversion of naloxone to over-the-counter to reduce access barriers and increase demand, the conversion could also result in an increase in out-of-pocket price for consumers, which would moderate the demand-side effects.”

Using a nationwide longitudinal prescription claims database the CHERISH investigators estimated the demand and supply functions for naloxone purchased at US retail pharmacies, which allowed them to estimate the own-price elasticity of naloxone demand in these settings, and ultimately predict retail pharmacy sales following conversion of naloxone to OTC. Using a generalized structural equation model, the investigators found that for every 1% increase in the out-of-pocket price paid for naloxone, there would be a 0.27% decrease in pharmacy sales. Applying this estimated own-price elasticity of demand for naloxone to estimates from the literature of changes in demand and price following conversions of other medications to OTC, the authors predict an increase in naloxone sales of 15%- 179% following its conversion to OTC. Dr. Murphy states “one hopes that the increase in naloxone sold at retail pharmacies would decrease the number of fatal opioid overdoses; however, this will depend on whether the changes in the marketplace result in an increase in the amount of naloxone among persons most likely to encounter an opioid overdose.”

Impact of State Policies for Prescription Drug Monitoring Programs on High-Risk Opioid Prescriptions

A recent study in Health Affairs by CHERISH Research Affiliate Dr. Yuhua Bao and CHERISH investigators Dr. Zachary Meisel and Dr. Bruce Schackman examined the impact of prescription drug monitoring program policies on high-risk opioid prescriptions. Prescription drug monitoring programs (PDMPs) are statewide databases of controlled substances dispensed at retail pharmacies. Currently, all states and Washington D.C. except Missouri have operating PDMPs that allow prescriber access. In her previous work with Dr. Schackman and Dr. Brandon Aden, Dr. Bao evaluated the effects of different PDMP use mandates on opioid prescriptions in the Medicaid population, finding a reduction in the use of Schedule II opioids by Medicaid enrollees in states with registration and use mandates. In this study Dr. Bao and colleagues focus on the effects of comprehensive use mandates, prescriber delegate legislations and interstate data sharing on high-risk opioid prescriptions in commercially insured patients. High-risk opioid use was defined by multiple overlapping opioid prescriptions, opioid prescriptions from more than 3 providers which could indicate doctor shopping, overlapping opioid and benzodiazepine prescriptions which increases risk for overdose, and high dose opioid prescriptions as indicated by a daily average morphine milligram equivalent of 120 or more.

Using a natural experiment design, investigators found that comprehensive use mandates requiring physician use of the PDMP were associated with a 9.2% reduction in the probability of overlapping opioid prescriptions, a 6.6% reduction in the probability of having 3 or more prescribers, and an 8% reduction in the probability of having overlapping opioid and benzodiazepine prescriptions. They did not observe an immediate effect on high dose opioid prescriptions although the estimated effect strengthened over time. Policies that allow prescribers to delegate access to office staff or other licensed professionals to reduce physician burden were associated with a 7.2% reduction in opioid prescriptions from more than 3 providers, a 4.3% reduction in high dose opioid prescriptions and a 1.8% reduction in overlapping opioid and benzodiazepine prescriptions, which strengthened overtime. Interstate Data Sharing that allow prescribers to view prescriptions in neighboring states were associated with a 2.6% reduction in having 3 or more prescribers, and an 2% reduction in overlapping opioid and benzodiazepine prescriptions. A reduction in overlapping opioid prescriptions and high dose opioid prescriptions was seen overtime.

Taken together these findings could have significant public health implications. Adoption of comprehensive use mandate policies resulted in a 6-9% reduction in almost all measures of high-risk prescription for commercially insured individuals. This translates to 36,000 fewer people having overlapping opioid prescriptions and 44,000 fewer people with overlapping opioid benzodiazepine prescriptions, for the non-elderly, privately insured population alone. Reduced morbidity and mortality associated with the reductions in high-risk opioid prescriptions for the entire population are likely substantial.

CDC Guidelines Change for HCV Testing in Baby Boomers: Success in Affecting Clinical Practice

Hepatitis C virus (HCV) is a communicable disease that could lead to liver cirrhosis and hepatocellular carcinoma affecting baby boomers and all people who inject drugs (PWID) in particular. There are over 19,000 HCV-related deaths in the United States annually. HCV can be cured using direct-acting antivirals that can also reverse HCV-related liver injury. In 2012, the CDC released guidelines encouraging physicians to expand targeted HCV testing to include all baby boomers (persons born between 1945 and 1965) in addition to other high risk groups such as PWID.

To examine the impact of this guideline change on clinical practice, CHERISH mentee Dr. Josh Barocas recently published a study in Health Affairs that compares the rates of HCV testing among the baby boomer population and the population born after 1965 before and after the 2012 guideline change. CHERISH Investigator Dr. Laura White at Boston Medical Center is a co-author. Dr. Barocas’ study used MarketScan Commercial Claims and Encounters data, a nationally representative database of commercially insured patients, from 2010-2014. Although he finds increasing rates of HCV testing across both populations, there was a markedly higher rate of testing in the baby boomer population following the CDC guidelines that was not observed among adults born after 1965. When he expanded the study period to measure rates of testing 24 months following the guidelines he found a sustained increase in testing. The guidelines were released before current highly curative direct-acting antiviral treatment regimens were available, so we do not know how many were subsequently treated with the new regimens.


These findings indicate that the HCV testing policy change resulted in a sustained increase in testing among the target baby boomer population and consequently reduced the impact of the HCV epidemic in the United States. Dr. Barocas comments that a similar initiative may help increase screening in the population of people born after 1965, which includes young PWID who are at high risk for HCV infection but may not be identified by risk-based screening. Dr. Barocas and other CHERISH-affiliated researchers are currently conducting research on the impact expanding CDC testing guidelines to adults born after 1965. Dr. Barocas went on to say “since we have evidence that providers follow HCV testing guidelines, it may be time to expand the reach of those guidelines and routinely test younger adults who, through substance use, are at increased risk of HCV infection.”

Medications for opioid use disorder: who is receiving which treatment?

Dr. Jake R. Morgan Presents the results of his MarketScan analysis at the College on Problems of Drug Dependence (CPDD) in June 2017.

In response to the growing opioid epidemic in the United States there is an increased focus on expanding evidence-based treatment using medications prescribed for substance use disorder, especially medications that can be prescribed in outpatient settings including buprenorphine and naltrexone. The Surgeon General’s report on facing addiction in America describes substance use disorders as chronic illnesses requiring long term treatment similar to other less stigmatized illnesses, but until now there were no studies that compared several medications for opioid use disorder head-to-head in real-world outpatient settings. Using the MarketScan database of commercially insured beneficiaries, CHERISH investigator Jake Morgan, PhD along with CHERISH colleagues Bruce Schackman, PhD, Benjamin Linas, MD, MPH, and Jared Leff, MS and Boston Medical Center colleague Alexander Walley MD, MSc analyzed prescribing patterns and subsequent treatment discontinuation for injectable naltrexone, oral naltrexone, sublingual buprenorphine/naloxone, sublingual buprenorphine and transdermal buprenorphine medications for opioid use disorder (MOUDs).

From 2010 to 2014, Dr. Morgan found that the proportion of commercially insured individuals in the database diagnosed with opiate use disorder (OUD) increased 4 fold but the proportion of individuals with OUD receiving these medications decreased, indicating that the proportion of individuals diagnosed with OUD outpaced the utilization of MOUDs. Individuals who received MOUDs were more likely to be male, younger and have a co-occurring substance use disorder than those with OUD who were not receiving the medications. While the proportion of all individuals receiving MOUDs who received naltrexone (injectable or oral) and transdermal buprenorphine grew, it remains small at approximately 5% of all MOUDs analyzed. Discontinuation rates after 30 days were high among all treatment groups, ranging from 31% for sublingual buprenorphine/naloxone to 70% for oral naltrexone. After the first 30 days, the discontinuation rate was higher among those receiving naltrexone (injectable or oral) and transdermal buprenorphine.

The MarketScan database is a nationally representative database of commercially insured individuals that allows investigators to track the pattern of filled OUD therapy medications. However, stigma is one of the largest barriers to treatment and thus these data underestimate the prevalence of OUD since they only include individuals with an OUD diagnosis. The results may not be generalizable to publicly insured individuals who may face additional barriers to MOUD treatment. The high discontinuation rates reported in this study suggest that more efforts are needed at the provider, health system and policy level in order to increase access to MOUD and reduce treatment discontinuation.