Treating Opioid Addiction With Buprenorphine-Naloxone in Community-Based Primary Care Settings

Over the past year, my associate and I have treated over fifty patients ourselves with BUPRENORPHINE/Naloxone in a normal rural family practice in Victoria, Australia. Six have stopped treatment themselves and returned to using street narcotics. Five have reduced and withdrawn and are not using narcotics (but still using Benzodiazepines). Sixteen have paid employment, which they did not have when using street narcotics. Our main difficulty has been maintaining pharmacists in the district who are accredited to dispense.

Competing interests:   None declared

Andrrew Ashworth's comments on the unique properties of buprenorphine are important. The agonist and partial Mu antagonist features are responsible for ease of induction and stabilization successes with this treatment. The naltrexone, howerver, was added to avoid diversion and prevent administration of the drug by routes other than sublingually. When buprenorphine/naltrexone is taken as directed sublingually, the naltrexone component is not absorbed significantly.

Ira Mintzer

Competing interests:   None declared

Though the authors correctly point out that Buprenorphine is a partial mu antagonist, they appear to ignore its opiate kappa antagonist properties and thereby do not give sufficient credit to their method, nor do they seem to fully understand its success. As Rothman et al (1) have previously pointed out, by combining Buprenorphine with a mu blocker, it effectively becomes an exclusive opiate kappa blocker. Thus the treatment described here is as much a step change as H2 receptor blockers were from antacids and vagotomies in the treatment of dyspepsia.

While mu agonists serve to "drive¨ dopamine into the nucleus accumbans (a mood centre) via GABA neurones, kappa agonists are presynaptic inhibitors of dopamine neurotransmission. I have previously postulated (2) that much of adolescent dysfunctional behaviour can be explained by a previously steady state balance of endorphin and dynorphin (a chronic, long-lasting, antinociceptives kappa agonist) in abused children being disrupted by the removal of regular abuse (and therefore endorphin secretion) leaving the chronic kappa agonist endogenous pain reliever unopposed. Previously abused individuals seek a sense of normality (normal dopamine neurotransmission) by driving a system inhibited by unopposed dynorphin using exogenous endorphin stimulation such as risk taking & self harm, or substitutes such as Heroin. Treatment using methods designed to change the mu/kappa balance such as low frequency Trans Cutaneous Nerve Stimulation have been effective in these patients (3), giving weight to the concept that endogenous opiate kappa activity is the driving force behind individuals' behavioural attempts to correct their own internal opiate balance.

If kappa blockade by the combination of Buprenorphine and Naloxone increases Dopamine secretion in the nucleus accumbens it may do so elsewhere, particularly in the centres regulating blood pressure. In view of the cardiac event reported here, perhaps this treatment should be associated with close monitoring of blood pressure and early intervention with antihypertensives.

Dysfunctional behaviours in young people have a high political profile; the early success of treatments designed to address abnormally high endogenous kappa agonists by achieving balance with legal mu agonists such as Methadone and LAAM have reduced research into the neurochemistry of so called ¨addiction¨. Simple pharmacological treatments based on blockade of the causes of addiction are attractive to family physicians but they will threaten a burgeoning "addictions industry¨ that has itself become addicted to long acting mu substitutes.

1 Rothman R.B., Gorelick D.A., Heishman S. J., Eichmiller P.R., Hill B.H., Norbeck M.S.W., Liberto J.G. An open-label study of a functional opioid antagonist in the treatment of opioid dependence. Journal of Substance Abuse Treatment 18 (2000) 277-281

2 www.bmj.com/cgi/eletters/bmj.38790.495544.7Cv1#131910

3 BMJ, Feb 2007; 334: 327 ; doi:10.1136/bmj.39121.857569.1F

Competing interests:   None declared

I agree completely with Dr. Fiscella's thoughts about buprenorphine-- it is an effective treatment and can support patients in making positive change in their lives. We have also found it interesting that it may be difficult to predict which patients will do well and be sober in 6 months. Employment and older age may be factors as well as attending self-help meetings. Yet socio- economic status and place of residence did not seem to predict success and in fact patients who were devastated by opiate use and suffered major losses as a result often experienced major successes when they stabilized on buprenorphine-naloxone. I agree that we need to have additional numbers of physicians who are trained and certified to prescibe buprenorphine. We would also benefit from increase in availability of counseling and group treatment.

Competing interests:   None declared

There are an estimated 800,000 persons who are opioid dependent in the United States including a growing number who are dependent on prescription opioids including hydrocodone and oxycodone. Yet less than one in four patients receive methadone maintenance treatment - in part due to community opposition to establishment of such programs.

Buprenorphine fills an important niche. It is a mixed opioid - it has both agonist and antagonist properties with a ceiling on its opioid effects. It provides an additional treatment option when methadone maintenance is not appropriate or is not available. It provides a means for safe outpatient detoxification of patients dependent on opioids (methadone cannot be used for this purpose outside of licensed programs). It also provides a means for treating chronic pain patients who are dependent on or are abusing conventional opioids.

Although Congress recently increased the number of patients that physicians may treat with buprenorphine to 100, the primary obstacle to more widespread use of buprenorphine (in addition to the cost of the drug) has been the lukewarm response from primary care physicians. Only about 10,000 physicians of any specialty have undergone the 8 hour training and become certified to prescribe it and only half of this number actually prescribe it.

Thus, the findings by Mintzer et al are timely. These findings demonstrate that it is feasible for primary care physicians to treat opioid dependence in the community and achieve reasonable outcomes. While diversion is a problem with any controlled drug, the risk of lethal overdose is far lower for buprenorphine than with pure agonist opioids. In contrast, rates of lethal overdose from methadone (mostly through prescription for pain) have risen sharply in recent years. Illicit injection use of buprenorphine is also deterred by prescribing the coformulation of it with nalaxone (Narcan), marketed under the trade name Suboxone.

Competing interests:   None declared

Our study revealed that 54% of patients were sober at 6 months. This was comparable to outcomes experienced in methadone maintenance and contrasts to 5 to 20% sober after short-term detoxification alone. Patients once stabilized on a maintenance dose of buprenorphine-naloxone were seen monthly and were given a 4 week prescription as well as monitoring patient's connection to counseling and self-help meetings. We believe that regular follow-up, attending self-help meetings , time limited prescriptions and the relationship with the primary care provider were all factors in successful outcomes. Clearly 46% is still a high relapse rate. Dr. Blondell's concern about diversion and relapse is important. Generally patients diverting medication to the illicit market have relapsed and do not return for follow-up treatment. Given the chronic nature of this illness, more treatment options are required. We believe that office-based treatment should be expanded to meet patient's needs when they are prepared to make changes in their lives.

Competing interests:   None declared

Mintzer and his colleagues have advanced our understanding of how primary care physicians might use buprenorphine-naloxone to treat opioid dependent patients (1). They report on their real-life experience treating patients in busy inner-city primary care practices. They have demonstrated that this sublingual pill can be used safely and effectively, with 54% of their 99 patients maintaining sobriety at six months.

Furthermore, Mintzer at al. have shown that the treatment of opioid dependent patients with buprenorphine-naloxone can be readily integrated into a primary care practice without disruption or needing to deal with behavioral acting out. Perhaps most importantly, this study demonstrated a trend toward better outcomes for patients who attended self-help meetings. This finding underscores the importance of combining medication and psychosocial interventions in the treatment of persons with addictions. Montoya et al., for example, demonstrated improved outcomes with group therapy for patients treated with buprenorphine (2).

The work of Mintzer et al. should be encouraging to primary care physicians who either have hesitated to become certified to prescribe buprenorphine-naloxone or have become certified but have not yet started to prescribe it.

References.

1. Mintzer IL, Eisenberg M, Terra M, et al. Treating opioid addiction with buprenorphine-naloxone in community-based primary care settings. Ann Fam Med 2007;5:146-150.

2. Montoya ID, Schroeder JR, Preston KL, et al. Influence of psychotherapy attendance on buprenorphine treatment outcome. Journal of Substance Abuse Treatment 2005;28:247-254.

Competing interests:   None declared