Buprenorphine and Naloxone Legislative Restrictions: A Compromise Towards Harm Reduction

Limiting access to MAT can result in patient harm. Improving access using a bridge therapy model may help save lives.

There were approximately 64,000 deaths from opioid overdose in 2016, including deaths from both prescription and illicit drugs. The incidence of opioid overdose has continued to escalate despite a number of efforts. Increasing treatment beds, limiting opioid prescriptions, distribution of naloxone and other efforts have not demonstrated a significant impact on non-medical opioid use or on opioid-related deaths.

The continuing rise in opioid overdose and overdose death has resulted in the declaration by the current executive administration of the opioid epidemic as a “Public Health Emergency”.

Medication assisted treatment (MAT) with agents such as methadone or buprenorphine/naloxone has been demonstrated to be one of the more effective measures in the reduction in high-risk opioid use among individuals with substance abuse disorder. Specifically, treatment with buprenorphine/naloxone has demonstrated efficacy in harm reduction with the advantage of a reduced potential for abuse, a safer therapeutic profile than alternatives, and it can be safely prescribed in the outpatient setting. Use of this therapeutic however, is currently restricted to only certain licensed providers in certain clinical settings, limiting access to this important life-saving intervention.

This was meant to be a safeguard such that the delivery of this therapeutic agent was controlled and coupled with educational efforts and with coordinated care. These efforts have merit, but also in effect limit the availability of this drug to patients who might otherwise benefit.

There is evidence that other treatment settings, specifically primary care providers and emergency departments (ED), have potential for reducing opioid overdose death and high-risk opioid use behaviors. The current policy around this drug limit this however and has created a barrier to access to this important medication. This raises the question, what is the real reason behind limiting this effective therapeutic, and what efforts can be made to improve access?

The opioid epidemic and MAT

Medication assisted treatment (MAT) is an effective intervention toward reducing opioid use among individuals with substance abuse disorder. In the United States, MAT takes several forms. Methadone is a widely used MAT program that typically involves patients presenting to a clinic on a daily basis to receive their dose. Methadone has a proven track record of efficacy, but the means of distribution has limited access to many, especially in rural areas.

Naltrexone is a once-monthly depot injection that requires at least seven days of opioid abstinence before initiation but has demonstrated efficacy in achieving abstinence and has the advantage of once-monthly dosing. Naltrexone does seem to have some benefit, particularly in certain populations, but recidivism rates remain high. The need for abstinence prior to initiation seems to be the most significant barrier.

Buprenorphine/naloxone is an FDA approved office-based treatment for substance use disorder (SUD). Buprenorphine-naloxone also has demonstrated efficacy in the treatment of SUD and can be used in the office and the outpatient setting, an advantage over methadone. There is no “washout” period as is required with naltrexone, so it can be started in patients even with recent opioid use. Despite these advantages and efficacy, the use of this drug is restricted to prescribers with special licensing.

Buprenorphine’s pharmacologic profile is well suited for medication assisted treatment (MAT) in opioid dependence. When combined with naloxone, the risk of overdose is significantly reduced as is the potential for abuse. There is less risk for respiratory depression and less sedation than is seen with methadone. The use of buprenorphine-naloxone combination therapy is a safe and effective means to provide MAT. Despite the efficacy of this drug however, patient access to these treatments are restricted in the United States.

There are only around 32,000 licensed prescribers at present, who are permitted to prescribe it under the current regulations. In addition, these prescribers can only prescribe to a limited number of patients and they are widely distributed geographically. As a result, this drug is effectively being rationed by regulation, despite a critical need. There is an opportunity to re-evaluate the legislation, allowing for well-educated but more permissive use in several settings, including acute presentations in the ED. A more permissive use of buprenorphine/naloxone could be of benefit in the acute setting of overdose or in those seeking detox, as has been seen in other more liberal prescribing environments.

Buprenorphine Legislation

Legislation enacted in 2000 limits prescribing of buprenorphine/naloxone by the Food and Drug Administration (FDA) for the indication of MAT. Providers must meet certain qualifications, including holding an active state license, registration with the DEA and must also have one or more of the following qualifiers; hold a subspecialty board certification in addiction psychiatry from the American Board of Medical Specialties, an addiction certification from the American Society of Addiction Medicine (ASAM), a subspecialty board certification in addiction medicine from the American Osteopathic Association or have completed a required eight-hour training for the treatment and management of patients with opioid use disorders.

This regulation also incorporates language that mental health services will also be provided along with the MAT therapy and that there is a restriction regarding the individual physician case-load to a total of 100 active patients. While MAT is overall a federally regulated practice, oversight is in fact multifactorial and involves the individual states, Substance Abuse and Mental Health Service Administration (SAMSHA), the Drug Enforcement Agency (DEA) and the Department of Health and Human Services (HHS).The SAMSHA oversees the implementation and accreditation of MAT programs under provisions set forth in the Certification of Opioid Treatment Programs, 42 Code of Federal Regulations (CFR) 8 and SAMSHAs Division of Pharmacologic Therapies is evaluates whether opioid treatment programs (OPT) are improving treatment, but not required to report if OPTs meet regulatory requirements.

Implications of Regulation

The current federal regulations restrict the use of buprenorphine/naloxone to use in an office-based setting by specially licensed prescribers. In addition, there are limitations to the number of patients any one prescriber can treat. The argument for this restriction was that legislators where concerned about adding another opioid to the market given the potential for abuse and for entry into the black market.

While this is a legitimate concern, Buprenorphine is an agonist-antagonist which has a ceiling effect for the desirable effects of opioids. The combination product has the added safety feature of the antagonist naloxone which further helps to reduce misuse. Considering the prescribed volume of more addictive, rapid-onset opioid prescriptions, some 240 million per year, these perceived risks are quite low in comparison.

The illicit market that has evolved for this drug is one in which most commonly, patients with substance use disorder are trying to “self-detox” using this drug. This carries a significantly greater risk than if the drug were appropriately prescribed. Additionally, more widely prescribed drugs, such as oxycodone and hydrocodone have a much greater black-market appeal and are the most common drugs of prescription drug misuse.

The limitation of patient volume is essentially policy driven by anecdote. The patient limit is an arbitrary number imposed by legislators, again feeling concern for adding another potentially addictive opioid to the market. Despite heavy recruitment, only approximately 31,000 of the possible 800,000 potential prescribers have the license to prescribe buprenorphine-naloxone. This in essence creates an artificial “drug shortage”, and thus limiting access to patients who might benefit from this treatment. This is despite evidence that access can lead to harm reduction.

In France, where access to buprenorphine-naloxone is not similarly limited, there were demonstrable improvements in treatment success, improved social conditions and reductions in HIV and Hepatitis C.Abuse of the combination drug did persist, but was less than 10% and the incidence appears increased when patients receive sub-therapeutic dosing.

The legislation also imposed an educational requirement for prescribing buprenorphine-naloxone. This should be applauded and should in fact be a requirement for the prescribing of an array of pharmaceutical agents. No such program is required to prescribe other opioids, which have a much greater risk for abuse. This program can serve as a model for other high-risk prescriptions, including not only opioids but benzodiazepines and amphetamines as well. This educational program can be further developed to include overall safe prescribing, including topics on safe medication handling and disposal as well as screening for substance use disorder. Instead of creating a barrier, educational programs of this nature can be integrated into the initial application and renewal process and will enhance safe prescribing practice for a variety of high risk medications.

In the meantime, the numbers of deaths from opioid overdose continue to rise. Buprenorphine-naloxone combination treatment is being rationed such that only a small number of individuals have access. Given that there are an estimated 20 million Americans with some form of SUD, expanded access to treatment is sure to be of benefit.

As an example, West Virginia has the highest number of overdoses per capita at 52 per 100,000, but only seventy-three registered buprenorphine-naloxone prescribers. This is one prescriber for every 25,000 people in the state. Similar disparities exist for some of the poorest regions in the country, limiting access to marginalized individuals. As with other public health emergencies, there should be efforts to improve access, not limit it. The FDA put forth efforts to increase access to anti-retroviral agents during the AIDS epidemic as well as influenza vaccine during influenza season and a similar approach should be utilized with buprenorphine-naloxone.

Rationing by Regulation

Allowing for more liberal prescribing will improve access to MAT, which is desperately needed as the opioid epidemic surges forward. This is one of the few interventions that has some demonstrated efficacy for maintained abstinence or decreased high-risk opioid use. Again, with no similar regulation for prescribing opioids, despite the unquestionable potential for harm, it makes little sense to limit a potentially effective if not life-saving treatment. It is egregious to restrict access to a reasonably safe and effective therapy, one which can potentially save thousands of lives, based simply on anecdotally-based legislation rather than on need. Rationing occurs when we limit the use of an evidence-based treatment, especially when there isn’t any other alternative. In healthcare as well as in life, rationing is necessary and common. Rationing becomes unethical when it occurs without justification or reason.

Buprenorphine-naloxone is being rationed not because of scarcity of this resource, but because of a regulation. This is further compounded in that access is based on proximity to a provider who has received the certification to prescribe this drug, as well as provider patient-load and provider willingness to treat any one individual patient, all of which tend to limit access to marginalized patients and those most in need.

Financial restraints also play a significant role in that patients who can’t afford this drug do not get it. While this is not a new problem, as many Americans struggle with health-care costs, this is a public health crisis that has heavily targeted low-income and marginalized individuals. There is evidence that drug manufacturers specifically targeted these low-income markets and the opioid consumption in these marginalized areas were astronomical. As with any pharmacologic therapeutic, cost is an issue, but rationing in this instance actually has the potential to increase cost. Limiting prescribers creates a market that reduces competition and thus a supply-demand model that is not equitable. Eliminating this market, by increasing the supply of prescribers, is at least one way to make this a more affordable therapeutic option.

One solution to this would be to amend the regulation for the prescribing of buprenorphine/naloxone. While the system in place is reasonable for long-term prescribers with a persistent case load and established practice, there should also be an opportunity for bridge-therapy using this agent. This would allow for any prescriber to provide a seven-day supply of treatment to help bridge patients to more definitive management. The bridge therapy would allow prescribers confronted with a patient with SUD to provide short-term, interim treatment, which could be an important harm-reduction intervention.

The seven-day bridge could be utilized by primary care providers, emergency medicine practitioners or any specialty that may have patients in need of treatment for SUD. This is a reasonable compromise to the current restrictions, is in compliance with the new opioid prescription policy that many states have adopted and could be a very effective means of providing real-time harm-reduction in this patient population.

There have been several studies that have demonstrated the effectiveness of short-term treatment, including emergency department prescribing of buprenorphine-naloxone combination therapy. Emergency department (ED) providers are well versed in dealing with patients suffering from substance abuse and are often in the position to provide potentially life-saving interventions in real-time. This has been demonstrated in several studies on both the use of naloxone prescribed from the ED, as well as pilot trials with buprenorphine-naloxone combination therapy. In these studies, short-term treatment resulted in harm-reduction, with decreased rates of recidivism and death.

Primary care providers (PCP) are also being turned to by patients for help with substance abuse. The provider-patient relationship in this setting is likely much more intimate than that of a separate suboxone-prescriber, given that the PCP is involved in the overall care and well-being of the patient. In addition, PCPs are more likely to provide follow-up and to ensure that the patient engages in cognitive behavioral therapy or other substance abuse programming. Primary care providers are equipped to follow a patient’s longitudinal recovery, engage in screening and to investigate other treatment programs as needed. Unfortunately, few PCPs are prescribers owing to a variety of issues including institutional support, patient volume and cost.

While less equipped for long-term treatment, other specialties such as surgery, orthopedics and even OBGYN could potentially provide a patient with a bridge to treatment with a short course of buprenorphine/naloxone in the appropriate setting. While this would require appropriate education and training, monitoring and data collection, a seven-day bridge could prove to be a useful harm-reduction practice in this epidemic.

Discussion

There is good evidence that an amended regulation allowing for a seven-day bridge of MAT in the form of buprenorphine/naloxone could be a useful harm reduction tool. A revision that allows any prescriber with appropriate DEA prescribing privileges for controlled substances to provide a sven-day bridge treatment to patients with SUD would allow for real-time harm reduction, allowing patients to seek more definitive treatment in the early stages of recovery. The bridge would limit the potential for abuse and could be regulated similarly to regulations put on first time opioid prescriptions in other settings.

Prescribing of this agent should be part of a continuum of care for patients with substance abuse and needs to be in the hands of those providers on the front lines of this epidemic including ED providers, PCPs and other specialists. It should be coupled with education just as much as the prescribing of opioids for analgesia should be. To otherwise restrict this agent is unnecessary rationing and based only on anecdotal assumptions. Most importantly, it is restricting a life-saving therapy in the midst of a public health crisis.

The death rate from opioids has reached epidemic proportions and continues to rise. In addition, marginalized, underserved and disadvantaged populations who may most need these services are the most likely to lack access in the current model. The concept of bridge treatment is an opportunity to think outside the box and put our patients, wo is in desperate need of treatment, first and foremost.

 

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