Buprenorphine and the Opioid Crisis: A Primer for Congress
Released: 2018-12-07T00:00:00

Introduction

Buprenorphine is one of three medications currently used in medication-assisted treatment of opioid use disorders. As such, buprenorphine's effectiveness, safety, and availability are of considerable interest to policymakers seeking to address the ongoing opioid crisis in the United States. During the 115 th Congress, committees held hearings on opioid-related topics such as implementation of the Comprehensive Addiction and Recovery Act of 2016 (CARA, P.L. 114-198 ), the effects of the opioid crisis on families, and opioid use among veterans. Members have introduced more than 150 bills related to opioids. On October 24, 2018, President Trump signed into law H.R. 6 , the Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act (the SUPPORT Act; P.L. 115-271 ), a broad measure designed to address widespread overprescribing and abuse of opioids in the United States. Congressional actions taken in recent years to address the opioid crisis, including the SUPPORT Act, have included attempts to increase access to buprenorphine.

Among the U.S. population aged 12 or older, an estimated 11.4 million individuals (4.2%) used heroin, misused prescription pain relievers, or did both in 2017. This includes over 2 million people (0.8% of the U.S. population aged 12 or older) who met full diagnostic criteria for an opioid use disorder. A minority of those with a substance use disorder receive specialty treatment. In 2016, 21.1% of those with any opioid use disorder received specialty substance use treatment, including 37.5% of those with heroin use disorder and 17.5% of those with prescription pain reliever use disorders.

About This Report

This CRS report attempts to answer questions policymakers may have about the following topics:

the effectiveness of buprenorphine as a treatment for opioid use disorder, the demand for buprenorphine as a treatment for opioid use disorder, and access to buprenorphine as a treatment for opioid use disorder.

The information about effectiveness in this report is based on a systematic review of research on buprenorphine. A systematic review is a comprehensive report collating all of the relevant empirical evidence on a specific topic. A more thorough explanation of the methodology for the systematic review of the literature, including all citations on which much of the information in this report is based, is available in the Appendix . The report focuses on buprenorphine as a treatment for opioid use disorder for adults. It does not provide a comprehensive overview of opioid abuse as a public health or criminal justice issue.

Effectiveness of Buprenorphine

Whether buprenorphine (or any medication) is effective is not a simple "yes" or "no" answer, for several reasons. Buprenorphine comes in different formulations, each of which has been evaluated separately. Studies may define effectiveness in different ways and may compare buprenorphine to different treatments (e.g., another medication or a nonpharmacological treatment). Also, effectiveness is weighed against safety risks. Finally, buprenorphine may be more effective for some people, or in some circumstances, than in others. The following sections address these topics.

What is buprenorphine?

Buprenorphine is a partial opioid agonist, meaning it binds to the same opioid receptors in the brain as full opioid agonists (such as heroin or methadone) but activates the receptors less strongly. Similar to methadone, buprenorphine can reduce the cravings and withdrawal symptoms that often accompany discontinuation of the opioid of abuse, but buprenorphine does so without producing the same euphoria or "high." As a partial agonist, buprenorphine offers less potential for abuse and has a lower overdose risk than methadone.

Buprenorphine was first approved by the Food and Drug Administration (FDA) as a pain reliever in 1981. Research on buprenorphine as a pain analgesic showed mixed effectiveness, though the drug did demonstrate lower rates of abuse than other opioid pain medications such as oxycodone. More than 20 years after it was first approved to treat pain, buprenorphine was approved by FDA as a treatment for opioid use disorder, under the trade names Subutex® and Suboxone®. The difference between the two products is that Suboxone® combines buprenorphine with naloxone – an opioid antagonist that blocks opioid receptors from being activated and thereby reduces the risk of abuse. Since 2002, FDA has approved other forms of buprenorphine (with and without naloxone) for the treatment of opioid use disorders, as shown in Table 1 .

Is buprenorphine an effective treatment for opioid abuse?

Overall, research on buprenorphine has found it to be an effective medication for maintenance treatment of opioid dependence. A 2014 review of buprenorphine efficacy trials conducted by Cochrane found that buprenorphine can be useful in helping individuals discontinue opioid drug use and maintain abstinence. The efficacy of buprenorphine in reducing opioid use, however, appeared to be dependent on several factors. For example, buprenorphine effectiveness seems to be dose dependent. It was only found to be superior to placebo when used at high doses. Buprenorphine was most effective when used at 16mg daily doses or higher, compared to low or medium doses of 15mg or less. The standard of care for buprenorphine treatment currently includes "flexible dosing" which involves individual clinicians determining dose based on each patient, rather than fixed dosing consisting of predetermined dosage regimens. Other factors influencing the effectiveness of buprenorphine include primary opioid of use (i.e., prescription pain medication versus heroin) and length of buprenorphine treatment (see questions below for further elaboration).

How does buprenorphine compare to other treatments for opioid abuse?

When compared to methadone (the most common treatment for opioid abuse), buprenorphine appears to be equally as effective in promoting abstinence from drug use. Buprenorphine offers several benefits compared to methadone. Buprenorphine has less potential for abuse and overdose than methadone, and some research suggests it may be more cost effective. Abrupt discontinuation of buprenorphine leads to milder withdrawal symptoms than methadone. Individuals using buprenorphine, however, appear to drop out of treatment at higher rates than those using methadone. Table 2 describes various opioid treatment modalities.

How well does buprenorphine maintain people in treatment?

Treatment retention describes the rate in which individuals remain in substance abuse treatment. Retention is often essential to achieve the goals of the treatment, namely abstinence from drug use. Retention in treatment for individuals using buprenorphine increases linearly as both the dose of buprenorphine and length of time spent weaning off the medication increase. Put simply, research implies that as the dose of buprenorphine increases, retention in treatment improves. Similarly, with a longer period of tapering off the medication comes greater retention in the treatment. Taper length for buprenorphine is also associated with greater rates of abstinence from other opioids and successful completion of treatment. Therefore, the higher the dose of buprenorphine and the longer individuals are on the medication, the more likely they are to remain in treatment, abstain from opioid use, and successfully complete treatment.

Studies seem to indicate that methadone is better able to retain participants in treatment than buprenorphine, but it remains unclear why this is the case. It may be that buprenorphine, being a partial opioid agonist, is less satisfying than methadone because it does not produce a comparable euphoric effect. Also, buprenorphine may not typically be increased to effective doses quickly enough, resulting in more attrition early in treatment. It is also possible that buprenorphine does not retain people as well because mild withdrawal symptoms from the opioid of abuse may still be present for many patients while using the medication. Being only a partial opioid agonist, buprenorphine is also easier to discontinue without withdrawal symptoms of its own, which may make dropping out of treatment less difficult.

Are there any risks to buprenorphine?

Buprenorphine is an opioid itself and therefore carries a risk for addiction and overdose. As a partial opioid agonist, the euphoric effects of buprenorphine are low compared to full agonists like heroin, fentanyl, morphine, or methadone. Therefore, the abuse potential for buprenorphine is generally considered to be less than that of full opioid agonists. Overdoses caused solely by buprenorphine are rare, with most overdoses occurring when the medication is used at the same time as other drugs such as benzodiazepines or other sedatives. Other adverse events associated with buprenorphine diverted intravenously, such as the transmission of communicable diseases, are similar to those of other misused injected substances. When buprenorphine is combined with naloxone, an opioid antagonist, it discourages misuse via injection which may contribute to buprenorphine's lower rates of abuse and overdose.

How safe is buprenorphine compared to methadone?

Preliminary evidence on buprenorphine suggests it may be a safer treatment compared to methadone. Buprenorphine has less abuse potential and appears to result in fewer fatalities than methadone. In one study, patients taking buprenorphine experienced half as many ambulatory care visits compared to those taking methadone, suggesting buprenorphine use was associated with fewer incidents endangering health and safety. Only a few studies have compared mortality rates between buprenorphine and methadone treatments; however, existing data suggest that methadone is associated with a higher potential for mortality in the first few weeks of treatment. Research indicates that rates of opioid overdose with buprenorphine are lower than those associated with methadone. Data from one study conducted in France showed that death rates attributable to methadone may be as much as three times greater than that of buprenorphine, though other studies found no significant differences. Comparison of the safety of these two treatments in the United States awaits further research.

Does buprenorphine work for everyone?

There appear to be differences in successful outcomes of treatment for opioid addiction based on whether an individual was primarily abusing prescription pain medication or heroin. When using buprenorphine for addiction treatment, heroin users seem to have less positive outcomes compared to individuals who abuse prescription painkillers. While both groups are retained in treatment at similar rates, those abusing pain medication demonstrate greater improvement when using buprenorphine. Also, several of the studies noted that more than ever before, heroin users began their drug abuse with prescription opioid medications. The effectiveness of buprenorphine treatment, therefore, may depend in part on whether an individual with opioid use disorder has transitioned from misusing prescription opioids to using heroin.

Demand for Buprenorphine

Buprenorphine is one of three medications currently used to treat adults addicted to opioids. The precipitous rise in opioid misuse in the last decade and increasing financial burden of this epidemic highlight the need for effective treatments. Despite marked increases in opioid abuse, deaths attributed to opioids, and related hospital admissions, the majority of individuals in need of treatment do not receive it.

What are the costs of the opioid epidemic?

Opioid overdose deaths have increased significantly in the past 15 years ( Figure 1 ). In 2015, an estimated 33,091 Americans died of opioid-related overdoses. In 2016, that number increased to 42,249. Data for 2017 revealed 47,600 deaths involving opioids, representing a fourfold increase over 2002, around the advent of the epidemic. Almost a third of patients prescribed opioid pain relievers misuse these medications, and an estimated 1 in 10 become addicted. Misuse of opioid pain medications remains high ( Figure 2 ). In 2017, an estimated 11.4 million people aged 12 and older misused opioids, including 11.1 million misusers of prescription pain relievers and 886,000 heroin users. While the majority of individuals who misuse prescription opioids will not progress to heroin use, they are 13 times more likely to use heroin in their lifetime than those who use pain medication as prescribed.

The financial costs of this epidemic have been substantial. The combined economic influence of the opioid epidemic (healthcare, labor, and criminal justice costs) was estimated at $92 billion in 2016, an increase of 67% from a decade ago. Another analysis, which included the cost of opioid overdose fatalities, estimated the cost of the opioid epidemic at $504 billion in 2015.

Access to Buprenorphine

Buprenorphine is regulated differently when used for opioid use disorder than when used for pain. The Controlled Substances Act (CSA) limits who may prescribe (or administer or dispense) buprenorphine to treat opioid use disorder, and the circumstances under which they may do so. These limits have implications for how patients gain access to buprenorphine and how they pay for buprenorphine. The different forms of buprenorphine (e.g., implants vs. sublingual, etc.) also have implications for how patients gain access to buprenorphine and how they pay for it.

Who can prescribe buprenorphine?

Buprenorphine may be used to treat opioid use disorder in two settings: (1) within a federally certified opioid treatment program (OTP) and (2) outside an OTP pursuant to a waiver. When used within an OTP, buprenorphine is administered or dispensed on site, rather than prescribed. That is, a patient does not receive a prescription to be filled at a retail pharmacy; instead, a patient receives the buprenorphine at the OTP, necessitating nearly daily visits to the OTP unless the patient is using injectable or implantable forms of buprenorphine which can last up to several months.

A physician or other practitioner (e.g., physician assistant or nurse practitioner) may obtain a waiver to administer, dispense, or prescribe buprenorphine outside an OTP. This is commonly known as a DATA waiver, drawing its name from the law that established the waiver authority: the Drug Addiction Treatment Act of 2000 (DATA 2000). Under the CSA, as amended by DATA 2000 and subsequent legislation, the requirement for separate Drug Enforcement Administration (DEA) registration as an OTP may be waived if both the medication and the practitioner meet specified conditions. To date, buprenorphine is the only medication to meet the conditions for the DATA waiver.

To qualify for a waiver, a practitioner must notify the Health and Human Services (HHS) Secretary of the intent to use buprenorphine to treat opioid use disorders and must certify that he or she

is a qualifying practitioner; can refer patients for appropriate counseling and other services; and will comply with statutory limits on the number of patients that may be treated at one time.

The patient limit is 30 individuals during the first year and may increase to 100 after one year or immediately if the practitioner holds additional credentialing or operates in a qualified practice setting. The patient limit may increase to 275 after one year under certain conditions specified in regulation.

The SUPPORT Act removed the temporary authority (through October 1, 2021) for qualifying nurse practitioners and physician assistants to obtain DATA waivers and expanded the definition of "qualifying other practitioners" to include clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives. Qualifying nurse practitioners and physician assistants may obtain waivers permanently, while clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives are authorized to obtain DATA waivers until October 1, 2023.

Why are there limits on the number of patients that can be prescribed buprenorphine by a single provider?

In the 1990s, the makers of buprenorphine argued successfully that opioid substitution therapy with buprenorphine need not be limited to OTPs, primarily because the safety profile of buprenorphine compared favorably to that of methadone. Congress remained convinced that opioid substitution therapy with buprenorphine should be subject to restrictions beyond those applicable when the same opioid medications are used to treat pain. The patient limit is one such restriction.

As originally enacted, DATA 2000 amended the CSA to allow qualifying physicians to treat opioid addiction using buprenorphine and imposed a patient limit of 30 individuals. This patient limit remains in place for qualifying practitioners that do not meet additional requirements. In 2006, the CSA was amended to allow a DATA-waived physician to increase the patient limit to 100 patients after one year. As aforementioned, subsequent legislation expanded eligibility for DATA waivers to other clinicians besides physicians.

Pursuant to a statutory provision authorizing the HHS Secretary to raise the patient limit through rulemaking, in March 2016, HHS issued a notice of proposed rulemaking that would have increased the patient limit to 200. The proposed higher patient limit was intended to significantly increase patient capacity for practitioners qualified to prescribe at this level while also "ensuring quality of care and minimizing diversion."

In response to public comments arguing that raising the patient limit to 200 was not likely to make a significant impact on addressing the treatment gap, HHS issued a final rule setting the patient limit at 275 after two years (subject to certain conditions). Using survey data, HHS found that an OTP could manage, on average, 262 to 334 patients at any given time. HHS set the new DATA waiver patient limit near the low end of this range, a conservative estimate of the number of patients who could be treated by a single physician in "a high-quality, evidence-based manner that minimizes the risk of diversion." The SUPPORT Act codified this number in law, allowing practitioners to increase the patient limit to 275 after one year of maintaining a waiver to treat up to 100 patients. The SUPPORT Act also amended the CSA to allow up to 100 patients to be treated immediately if the practitioner holds additional credentialing or operates in a qualified practice setting.

How has use of buprenorphine to treat opioid addiction changed?

As opioid abuse rates have increased, the federal government has made efforts to address this epidemic. Both Congress and the Administration have implemented policies intended to increase access to buprenorphine, such as changes to the DATA waivers described above. Policy efforts to address the opioid epidemic have corresponded with increased treatment availability. Since 2003, treatment capacity has increased and continues to rise. The number of OTPs offering buprenorphine increased from 121 (11% of all OTPs) in 2003 to 779 (58% of all OTPs) in 2015. The number of non-OTP substance abuse treatment facilities (non-OTPs) offering buprenorphine increased from 620 (5% of all non-OTPs) in 2003 to 2,625 (21% of all non-OTPs) in 2015. In total, the proportion of facilities (either OTP or non-OTP) providing buprenorphine treatment increased from 14% in 2007 to 29% of all facilities in 2017. The total number of facilities offering buprenorphine is depicted in Figure 3 . This does not include practitioners with office-based (as opposed to facility-based) practices. Data from SAMHSA's annual National Survey of Substance Abuse Treatment Services (N-SSATS) indicate that the proportion of clients at substance use facilities who receive buprenorphine has increased in the past decade, from less than 1% in 2007 to 8% in 2017.

The cumulative number of DATA-waived providers has increased also. The number of DATA-waived physicians with a 30-patient limit increased from 1,800 in 2003 to 16,095 by 2012, and those with a 100-patient limit expanded from 1,937 in 2007 to 6,103 in 2012. By 2012, the maximum number of patients who could be treated with buprenorphine in the United States was 1,093,150, a rate of 420.3 per 100,000 people aged 12 years and older. Due to this increase in DATA-waivers for buprenorphine treatment, nearly 3.5 times as many patients could be treated with buprenorphine in 2012 as were receiving methadone in 2012.

The Substance Abuse and Mental Health Services Administration (SAMHSA), which oversees the buprenorphine waiver program, provides daily updates on the number of DATA waivers. As of December 1, 2018, the number of DATA-waived providers with a 30-patient limit exceeded 40,000 and those with a 100-patient limit exceeded 11,000. The number of practitioners with a 275-patient limit totaled over 4,500. This provides the capacity for almost 3.6 million patients to be treated with buprenorphine.

Despite this increase, access to substance abuse treatment such as buprenorphine has not kept pace with the mounting rates of opioid addiction in the United States. In 2012, the difference between the number of people experiencing opioid dependence and the combined methadone and buprenorphine treatment capacity in the U.S. was nearly one million. Forty-eight states and the District of Columbia had higher rates of past-year opioid abuse than capacity for buprenorphine treatment in 2012. During that year, 82% of federally certified opioid treatment programs (OTPs) reported operating at 80% or greater capacity.

Admissions to substance abuse treatment facilities involving prescription opioids nearly quadrupled between 2002 and 2014. In 2015, 18.3% of individuals in need of treatment for an illicit drug problem, including prescription pain relievers, received it. In 2016, one-fifth (21.1%) of those with any opioid use disorder received specialty treatment, including 37.5% of those with heroin use disorder and 17.5% of those with prescription pain reliever use disorders. A study conducted in Massachusetts found that of individuals recently hospitalized for a nonfatal opioid-related overdose, less than one-third received any medication-assisted treatment in the 12 months following the overdose.

In addition, while the capability to treat patients with buprenorphine has expanded through an increase in DATA-waivers, practitioners with these waivers are not treating to capacity. A 2018 study by SAMHSA leadership found that the number of patients being treated by DATA-waived providers was substantially lower than the authorized waiver patient limit. The percentage of clinicians prescribing buprenorphine at or near the patient limit in the past month was 13.1%.

Geography may be relevant in understanding the treatment discrepancy: where services are located may be more important than the capacity for treatment in addressing the gap between need and availability. Other factors affecting the treatment gap besides location of services may include health insurance coverage, reimbursement for treatment services, transportation, stigma, awareness of treatment options and availability, and motivation for recovery among others.

How much does buprenorphine cost?

The cost of any prescribed medication is influenced by the pharmaceutical manufacturer, the insurer, the health plan or prescribing clinic, and the retail pharmacies that dispense the medication. It is difficult, therefore, to identify a precise figure for the cost of buprenorphine. The Department of Defense (DOD) and the National Institute for Drug Abuse (NIDA) have estimated the following costs:

methadone treatment: $126 per week ($6,552 per year) buprenorphine treatment: $115 per week ($5,980 per year) naltrexone: $1,176.50 per month ($14,122 per year)

Most of the research comparing the costs of medication-assisted treatments has found similar results, suggesting buprenorphine may be cheaper than other medications. Some studies, however, have been inconclusive or suggest the opposite. In one study conducted at a Veterans Affairs (VA) medical center, the average cost of care for six months of buprenorphine treatment was $11,597. The costs associated with methadone over that same time period were $14,921. The costs were not significantly different in subsequent months after the first six months of treatment, however. Indirect costs in that same study were also higher for the methadone group, which had twice as many ambulatory care visits as the buprenorphine group. Other estimates suggest that the costs of buprenorphine treatments may be as much as 49% lower than those for methadone. Preliminary studies on the subdermal formulation of buprenorphine approved in 2016 suggest that this type of treatment may have lower total costs than other forms.

Other studies have found buprenorphine treatment costs equivalent to, or slightly higher than, those for methadone. For instance, NIDA reported that the annual cost of methadone treatment may be closer to $4,700 per patient. The findings of a few studies may not be representative of the costs of buprenorphine (or methadone) in other VA medical centers or other settings. Determination of the cost effectiveness of buprenorphine, particularly compared to other treatment options such as methadone, awaits further research.

Does Medicare pay for buprenorphine treatment?

Medicare reimbursement for prescription drugs depends on the setting in which the drugs are used and how they are administered. In general, Medicare Part A covers drugs used as part of an in-patient medical treatment; Medicare Part B covers prescription drugs that are not usually self-administered and are furnished and administered as part of a physician service; and Medicare Part D covers FDA-approved drugs that (1) are available only by prescription, (2) are used for a medically accepted indication, and (3) are not covered under Parts A or B.

As noted previously, buprenorphine may be administered or dispensed (but not prescribed) in an OTP, and also may be administered, dispensed, or prescribed outside an OTP pursuant to a DATA waiver. Medicare does not recognize OTPs as covered providers, and does not provide Medicare reimbursement for buprenorphine dispensed in an OTP.

Medicare Part B has no separate benefit category for drugs used in the management of opioid use disorder. However, Part B will cover long-acting injectable and implantable forms of buprenorphine if administered by a physician and used in the management of opioid use disorder (referred to as "incident to a physician's services" by Medicare). Since January 1, 2018, Medicare Part B has provided a separate payment for insertion, removal, and removal with reinsertion of buprenorphine subdermal implants.

Part B does not pay for self-administered drugs used during a provider visit. For example, if a physician's office stocks sublingual buprenorphine, its use would not be paid under Part B because such forms of the drug are considered self-administered (thus not payable under the "incident to" benefit). Payment to a physician for the observation of self-administration of the drug by the patient (such as initial induction doses, for example) may be possible under Part B.

Medicare Part D plans must cover buprenorphine and other self-administered drugs used in MAT for opioid use disorder, either on their formularies (list of covered drugs) or via a coverage exception request by an enrollee. Part D plans also must provide a transition supply of drugs for new enrollees who are already in treatment for opioid use disorder. Part D plans are to place MAT drugs on lower-cost-sharing tiers, although beneficiary cost sharing might vary depending on the Part D plan. Medicare Part D does not cover oral buprenorphine or buprenorphine-naloxone combination products for the treatment of opioid dependency when they are administered or dispensed by OTPs. The Centers for Medicare & Medicaid Services has told Part D plan sponsors that they are expected to set low enrollee cost-sharing for MAT drugs, including buprenorphine.

Does Medicaid pay for buprenorphine treatment?

All 48 states that responded to a 2017 survey (Arkansas and Illinois did not respond) indicated that their Medicaid programs covered buprenorphine. Analysis of 2013-2014 survey data found that all 50 states and the District of Columbia covered buprenorphine and that 49 respondents imposed some limits, such as prior authorization requirements, duration of treatment, or per-day maximum doses. Even though state Medicaid programs cover buprenorphine, states may only cover certain buprenorphine forms or may only cover buprenorphine under certain conditions. For instance, a state Medicaid program may use a formulary that requires beneficiaries to enroll and attend MAT therapy or counseling before they can receive buprenorphine. States also may use a preferred drug list to require providers to use specific products first.

Concluding Comments

Buprenorphine is one of three medications currently used to treat adults addicted to opioids. The rise in opioid abuse in the last decade and substantial financial burden of this epidemic highlight the need for effective treatments. Overall, buprenorphine appears to be an effective medication for treatment of opioid dependence. Despite marked increases in opioid abuse, related hospital admissions, and overdose deaths, the majority of individuals in need of treatment do not receive it. Prescribing practices for buprenorphine as a treatment for opioid use disorder are carefully regulated and include provisions that limit the number of patients certain providers can treat simultaneously. Congress and the executive branch have made efforts to increase access to buprenorphine treatment while balancing potential risks of this opioid-replacement therapy. Congress is likely to continue grappling with the opioid crisis for some time, as policymakers and medical and public health professionals wait for new data to indicate whether existing efforts have changed the trajectory of the opioid epidemic. Striking a balance between providing access to buprenorphine and maintaining quality standards for those who prescribe or dispense it may prove challenging.

Appendix. Systematic Review

Report Methodology

Much of the information in this CRS report is based on a systematic review of the scientific literature on buprenorphine, undertaken in August 2017. A systematic review is a single comprehensive report collating all of the relevant empirical evidence on a specific topic. Systematic reviews use explicit, systematic methods to identify studies that fit pre-specified eligibility criteria. Systematic reviews have become an increasingly important source of information for clinical practice and policymaking. They synthesize large amounts of information and provide better estimations of performance and generalizability than individual studies.

CRS' systematic review aimed to determine how well buprenorphine works in the treatment of opioid dependence compared to other treatments (such as methadone) or no treatment at all. Studies were included if they were comparisons of buprenorphine with other interventions in outpatient community settings in the United States and were published in the past five years. These included primary and secondary analyses of randomized control trials, quasi-experimental studies, and cohort studies. The CRS review concentrated on effectiveness rather than efficacy (see textbox under " How well does buprenorphine maintain people in treatment? "). Therefore, studies were excluded from this review if they examined efficacy, occurred in inpatient settings, focused on withdrawal, or occurred outside the United States. To identify original articles that met the inclusion criteria, we developed a search strategy for each of the three scientific databases used. We searched PubMed life science and biomedical database, PyscINFO behavioral sciences and mental health database, and CINAHL nursing journal database through July 21, 2017.

Article Summaries

Table A-1 provides full citations and abbreviated references to the 16 articles identified above. Table A-2 summarizes each article, including its participants, study design and aims, and conclusions.