Summary¹

OPIOID USE DISORDER IS A TREATABLE CHRONIC BRAIN DISEASE

Addiction is a chronic disease that involves compulsive or uncontrolled use of one or more substances in the face of negative consequences. As with other chronic medical conditions, a confluence of genetic, environmental, and social factors shape a person's vulnerability to addiction and ease of recovery from it. These factors determine a person's propensity to start using drugs and to keep using them, as well as a person's susceptibility to the particular types of neurobiological changes in the brain that characterize the progression to addiction. Building on decades of research, the scientific community has coalesced around the brain disease model of addiction. In people with OUD and other substance use disorders (SUDs), prolonged and repeated drug use over time causes lasting effects on brain structure and function. Prescription and illicit opioids produce powerful and sustained effects on the brain's opioid system; repeated use can disrupt the regulation of the system and result in tolerance, physical dependence, and addiction. The evidence shows that these brain changes can be treated effectively with medications that help people refrain from using drugs, thus sharply reducing their risks of overdose and death. By alleviating opioid cravings and withdrawal symptoms, the medications can also provide opportunities to address the behavioral and social components of addiction, which are critically important both to the disorder's development and its treatment.

This scientific understanding of OUD is at odds with the prevailing public perception of the disorder, which is colored by the misconception of addiction as simply a moral failing. That popular view has proliferated through generations of social stigmatization directed at people who use drugs; this misinformed stigma has also spread to the medications used to treat OUD. In fact, people with OUD have a chronic disease that, like many others, warrants long-term medical management beyond episodic acute care incidents.

MEDICATIONS FOR OPIOID USE DISORDER SAVE LIVES

OUD is caused by changes in brain circuitry that can be treated with medication to restore healthy brain function, which leads to improvements in behaviors associated with addiction. The medications currently approved by FDA for treating OUD are evidence based, safe, and highly effective. Medication-based treatment for OUD focuses first on managing withdrawal symptoms and then on controlling or eliminating the patient's compulsive opioid use, most commonly with the agonist medications methadone or buprenorphine. Large systematic reviews and randomized controlled trials show that patients with OUD who receive these medications are less likely to die from overdose or other causes related to their addiction. Patients who receive medication have higher treatment retention rates, better long-term treatment outcomes, and improved social functioning; they are also less likely to inject drugs or transmit infectious diseases. For patients who have gone through withdrawal from opioids for a sufficient time, extended-release naltrexone may be used for maintenance treatment. Available evidence clearly supports the use of medications and the need to expand access to medications to reduce or eliminate compulsive opioid use, to reduce the risk of premature death, and to improve the quality of life of people with OUD and their families.

Methadone, buprenorphine, and extended-release naltrexone all work by targeting the mu-opioid receptor within the opioid system. Because each medication has a distinct mechanism of action, the most appropriate medication and dosage vary across patients and may vary in the same patient over the course of treatment. The existing medications are very effective, but they are not perfect; for example, evidence gaps remain about how to choose the most effective medication for a particular patient and how best to retain people in treatment, which is itself a significant problem. Moreover, because OUD has complex behavioral and social causes and consequences, it is not yet known which behavioral interventions might be most appropriate to help restore patients to full functionality. Therefore, even though there is a need to act urgently to improve access to existing medications, innovation cannot stagnate. Research should continue to focus on developing new and better medications to treat OUD, on determining the most effective behavioral therapies to maximize outcomes, and on refining the most appropriate protocols for their effective use.

Evidence demonstrates that patients who receive longer-term treatment with medication for OUD have better treatment outcomes; they are also less likely to die from overdose if they return to use while on medication. In fact, people with OUD are up to 50 percent less likely to die when they are being treated long term with methadone or buprenorphine. Further research is needed to define an optimal treatment regimen for each of the available medications and to directly compare the effects of the three medications' long-term use. Nonetheless, in spite of the need for more research, the body of evidence amassed over the past 50 years underscores the benefits of long-term retention on medication.

Treatment with a combination of medication and evidence-based behavioral interventions (e.g., contingency management approaches, cognitive behavioral therapy, and structured family therapy) can be effective for many people with OUD. However, little is known about which combinations of medication and behavioral interventions are most effective, which patients are most likely to benefit from behavioral interventions, and which patients may do well with medications and appropriate medical management alone. Even among patients who would benefit from the addition of behavioral interventions, it is better for them to receive medication with appropriate medical management than to have it withheld. The life-saving aspects of these medications have been established even in the absence of accompanying behavioral interventions. Given the resource limitations faced in many settings, it is critical that providers do not withhold medications from their patients just because behavioral interventions are not available.

MEDICATIONS ARE NOT AVAILABLE TO MANY PEOPLE WHO NEED THEM

Most people with OUD in the United States do not receive any treatment at all, and those who do receive any type of treatment may wait years to do so. Of the small proportion of people who do receive treatment, just a fraction receive medication. Access to evidence-based treatment is poor across the board, but it is starkly inequitable among certain generational, racial, ethnic, social, and economic groups. Although the research is not yet granular enough to develop tailored treatment guidelines for specific subpopulations, the available evidence supports the effectiveness of medication for treating OUD in all groups, including adolescents, pregnant women, and people with comorbidities. However, the treatment gap is exacerbated for vulnerable populations, whose members face steep barriers in accessing medications.

Access to medications for OUD remains inequitable across different treatment settings as well. In the United States, methadone can only be administered through specialty facilities known as opioid treatment programs (OTPs), even though the available evidence shows that delivering it through an office-based medical practice setting is also effective. Moreover, most residential treatment facilities do not offer medications, and if they do, they rarely offer all three medications.

Despite the large and increasing numbers of people with OUD entering the criminal justice system in the United States, evidence-based medications are often withheld or are only provided on a limited basis for medically supervised withdrawal. As a result, few people with OUD receive medication while incarcerated or under the supervision of drug courts. In addition, justice-involved people who do receive medication for OUD are often not linked with care upon release, leading to treatment discontinuation and the concomitant risks of overdose and death. Given that these medications are known to save lives, it is arguable that withholding them from persons with OUD is unethical, as withholding insulin or blood pressure medications would be.

Pharmacies, mobile medication units, community health centers, emergency departments, and other care settings provide opportunities to engage people with OUD and link them to evidence-based care. Expanding medications for OUD into a broader range of care settings would save lives and build the capacity to make real progress against the epidemic.

A number of barriers, both social and systemic, prevent people with OUD from accessing the life-saving medications they need. Making headway against the opioid crisis will require addressing barriers related to stigma and discrimination, inadequate professional education, overly stringent regulatory and legal policies, and the fragmented systems of care delivery and financing for OUD.

The stigmatization of people with OUD is a major barrier to treatment seeking and retention. Social stigma from the general public is largely rooted in the misconception that addiction is simply the result of moral failing or a lack of self-discipline that is worthy of blame, rather than a chronic brain disease that requires medical treatment. Evidence demonstrates that social stigma contributes to public acceptance of discriminatory measures against people with OUD and to the public's willingness to accept more punitive and less evidence-based policies for confronting the epidemic. Patients with OUD also report stigmatizing attitudes from some professionals within and beyond the health sector, further undercutting access to evidence-based treatment. The medications, particularly the agonist medications, used to treat OUD are also stigmatized. This can manifest in providers' unwillingness to prescribe medications due to concerns about misuse and diversion and in the public's mistaken belief that taking medication is “just substituting one drug for another.” Importantly, the rate of diversion is lower than for other prescribed medications, and it declines as the availability of medications to treat OUD increases.

Despite the mounting crisis, the health care workforce in the United States does not receive adequate, standardized education about OUD and the evidence base for medication-based treatment. This has created a shortage of providers who are knowledgeable, confident, and willing to provide medications to patients. Many rural areas are being overwhelmed by the opioid epidemic and have very few, if any, trained and licensed providers who can prescribe the medications. Misinformation and a lack of knowledge about OUD and its medications are also prevalent across the law enforcement and criminal justice systems.

Stringent laws and regulatory policies pose substantial barriers to methadone and buprenorphine access. Laws and regulatory requirements restrict outpatient methadone treatment to state- and federally certified OTPs, which is detrimental to long-term treatment adherence for many patients. Unlike methadone, buprenorphine is approved to be prescribed in office-based settings, but only by providers who undergo specialized training and obtain a waiver from the Drug Enforcement Administration. Few providers in the United States have such waivers (estimated at less than 3 percent), and additional regulations limit the number of patients that each provider can treat with medication. To compound the problem, most waivered providers prescribe buprenorphine at well below the capacity they are allowed. These policies are not supported by evidence, nor are such strict regulations imposed on access to life-saving medications for other chronic diseases.

The system of care delivery for OUD is fragmented and poorly integrated into the broader health system in the United States. Treatment settings and financing streams for SUDs are generally detached from primary care, further obstructing access to medications for OUD, especially among people with other co-occurring conditions. Many providers are reluctant to treat people with OUD because they do not receive timely and sufficient reimbursement by public and private insurance coverage, which often limits or excludes evidence-based medication treatment services for OUD. These barriers are compounded by other restrictions, such as prior authorization policies, dose limitations or forced dose tapers, counseling requirements, and annual or lifetime limits on the amount of OUD medication a person can receive. Almost half of nonelderly adults with OUD are covered by Medicaid, which has been shown to help connect people with medication-based treatment for OUD and to improve treatment retention. However, Medicaid coverage for OUD medications varies widely by state, with some states excluding methadone and buprenorphine entirely.

STATEMENT OF TASK AND STUDY METHODOLOGY

This consensus study was carried out by the committee between October 2018 and March 2019. Study activities included a comprehensive literature review of the effectiveness of medications for OUD and the barriers people face in accessing them. The committee held a 1.5-day public workshop in Washington, DC, which was summarized in a Proceedings of a Workshop—in Brief, as well as two 2-day closed committee meetings. The Statement of Task to the committee is provided in Box S-3.