Should the Government Repeal Restrictions on Buprenorphine/Naloxone in the Short-Term, Not the Long-Term?

There is a plethora of research indicating opioid dependence can be successfully treated with either buprenorphine alone or with buprenorphine in combination with naloxone (Suboxone®; Subsolve®). However, we encourage caution in long-term maintenance using these drugs, even considering the lack of any other FDA approved opioid maintenance compound to date. Our concern has been supported by severe withdrawal experience by patients from low dose of buprenorphine, alone or with naloxone (even with tapering of the dosage of for example buprenorphine, which is 40 times more potent than morphine).

In addition, our findings of a long-term flat affect in chronic Suboxone® patients (average 1.6 years), among other unwanted side effects, including diversion and suicide attempts, provide impetus to reconsider long-term utilization. However, it seems prudent to embrace genetic testing to reveal reward circuitry gene polymorphisms especially those related to dopaminergic pathways as well as opioid receptor(s) as a way of improving treatment outcomes. Understanding the interaction of reward circuitry involvement in buprenorphine effects and respective genotypes provide a novel framework to augment a patient’s clinical experience and benefits during opioid replacement therapy.

With this caveat and because there is increasing use of street heroin abuse, including among adolescents, we must be realistic and appreciate that to date there is no other viable approved option. There are many individuals that could benefit from utilization of buprenorphine/naloxone that are not receiving opioid replacement therapy. In 2000, Congress passed a law (DATA-2000) that allows physicians to prescribe the partial mu opiate receptor in combination with very low dosage of the narcotic antagonist naloxone (blocks IV diversion and subsequent abuse potential) to become certified. If clinicians take and pass an 8-hour course and meet certain qualifications, they become eligible to legally prescribe this approved medication. However, this law, void of any real science, restricts the number of patients that a physician could treat at any time to 30 through the first year following certification, expandable to 100 patients thereafter. Interestingly, no other medications have this restriction and many American Society of Addiction Medicine (ASAM) members and other physicians have called into question the benefit of such a law.

Tom McLellan, PhD, of the Treatment Research Institute, has stated, “The fact that patients are frequently denied access to the full spectrum of treatment options for addiction is unethical and would constitute malpractice in other medical specialties and chronic disease treatment.” Moreover, ASAM adopted a policy opposing any limitations on the availability of all FDA approved medications for the treatment of opiate dependence “via various utilization control mechanisms, including medication and testing and treatment supply quantity limits.”

There are some that would like to see the law eliminated and others that endorse an increase to 200 or 300 patients instead of the present restriction number. Certainly, the law had good intentions, primarily considering the addictive nature of buprenorphine (even if it has been argued as having less adverse effects than methadone, for example, but still very significant). In this regard, the work in my laboratory, in conjunction with Dominion Diagnostics, LLC, along with a number of ASAM physicians has utilized a sophisticated drug urine analysis, “Comprehensive Analysis of Reported Drugs (CARD)™” to evaluate both treatment compliance and abstinence from all abusable drugs including of cause opioids in 1,268 patients receiving Suboxone®. While we found a very high compliance of approximately 90%, our take home message following a longitudinal analysis revealed a very significant drop in opioid abuse (legal or illicit) in the urine. This finding potentially highlights that in specialized Intensive Opioid Replacement (IOP) clinics having appropriate counseling staff, among other modalities, the question of diversion seems to be significantly reduced.

Based on a number of recent neuroimaging and other neurobiological findings including utilization of an emotional reactivity as measured by an automatic detection in speech, my laboratory, along with groups from Montreal and MIT, and Charles Moehs, MD, found that long-term (1.66 years) Suboxone™ users have abnormal emotional experience (flat affect), characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli. This finding would suggest that the idea of long-term use of buprenorphine/naloxone combination for treatment should be reconsidered.

Nevertheless, we must realize that many patients addicted on opioids can benefit from at least short-term buprenorphine/naloxone treatment and that it is currently is the frontline treatment option. Moreover, these patients may carry genetic risk alleles that require opioid replacement therapy and until the so-called “Magic Bullet” for addiction treatment is discovered, we as an advanced society should intelligently reconsider the restrictive current law and understand the chronic nature of substance and non-substance seeking behavior as espoused in the concept of Reward Deficiency Syndrome (RDS).