In 2010, TCPR published an overview of Suboxone (buprenorphine/naloxone) (TCPR, May 2010). Lots has happened in the three years since then.

For starters, the American Society of Addiction Medicine (ASAM) issued a consensus statement in December 2011 on the office-based use of buprenorphine for opioid addiction treatment (Kraus ML et al, J Addict Med 2011;5(4):254–263). The purpose of the statement was to synthesize the literature on the clinical use of buprenorphine and to streamline general practice guidelines to encourage additional physicians to begin using buprenorphine, which was approved by the FDA for opioid dependence in 2002.

Thousands of physicians have obtained the special DEA waiver to prescribe buprenorphine. This allows them to treat up to 30 patients in the first year and 100 patients per year thereafter. The numbers peaked in 2008 with just over 3,000 freshly minted buprenorphine prescribers, but decreased in 2009, which saw the first drop in newly certified physicians. There was a negligible increase over the next two years and a significant drop to fewer than 1,500 new prescribers in 2012. As of 2012, a total of 22,283 physicians nationwide can prescribe buprenorphine, but only a quarter choose to maintain up to 100 active patients. With more than two million opioid addicts in the US, it’s obvious that demand outnumbers supply.

Prescribers have multiple reasons for not prescribing buprenorphine: the concern over DEA inspections and the pressures of monitoring for diversion and abuse; the challenges of treating addicts who often present with comorbid pain syndromes; and resource barriers that discourage physicians, especially solo psychiatrists, from obtaining the buprenorphine waiver. That said, it can be fulfilling and economically viable to treat patients with buprenorphine (Mark TL et al, J Subst Abuse Treat 2013;44(5):481–487).

Suboxone tablets became generic in 2010. In September 2012, Reckitt-Benckiser (Suboxone’s manufacturer) announced that it would pull the pill form off the shelves, due to the risk of children accidentally ingesting it. At the same time, they issued a “citizen’s petition” to the FDA requesting that anyone who wants to sell generic buprenorphine tabs be required to child-protect each tablet, and began marketing the new sublingual film formulation, the patent for which doesn’t expire until 2022 (Silverman, E. Reckitt’s Suboxone Strategy Is Really About Patients Or Profits? www.forbes.com; October 12, 2012).

Medication-Assisted Recovery vs Psychosocially-Assisted Pharmacotherapy

In 2012, the Hazelden Foundation, leaders in addiction treatment and champions of the 12-step philosophy and total abstinence since 1949, announced that they would start using buprenorphine in patients with more than a year of opioid dependence. This represents a historic turning point in their philosophy. They reported that they couldn’t ignore the painful experience of seeing their clients relapse—and sometimes die—soon after leaving treatment. Likewise, the ASAM consensus statement stated unequivocally that “medication-assisted therapies such as buprenorphine” are more effective than any other type of treatment for opioid dependence, although it also advised “psychosocial interventions, such as counseling and other psychosocial therapies.”

In an age where the neurobiological model of addiction is widely accepted, there is a push to call such treatment “counseling-assisted pharmacotherapy” as opposed to “medication-assisted treatment.” In a recent commentary entitled “Just Call It Treatment,” two authors (one of whom reports a financial interest in Reckitt-Benckiser) argue for the importance of terminology: “The view that pharmacotherapy-induced remission is less valuable than ‘real’ recovery,” they write, “stigmatizes patients, providers, and the therapy itself” (Friedmann PD and Schwartz RP, Addict Sci Clin Practice 2012;7(1):10). Although they do not devalue psychosocial interventions entirely, they point out that patients on medication often do better regardless of counseling.

Whether medication or therapy is the primary intervention, just calling it “treatment” might be a step in the right direction of destigmatizing addiction and bridging the divide between abstinence-based and harm-reduction recovery models. Diabetics receive education and counseling along with insulin, but one would never withhold insulin if the patient didn’t adhere to other forms of treatment. On the other hand, elevating pharmacological interventions over psychosocial ones in the treatment of addiction may encourage over-prescribing and hastily laid-out treatment plans. It may ignore the ever-present psychosocial, spiritual, and human characteristics of the addict. It may enable the addict to divert Suboxone to get cash for heroin, or overuse it to get a buzz. Suboxone will not guarantee one won’t relapse, and dependence on buprenorphine is always a risk. But buprenorphine can also save and transform lives.

Special Populations

In the MOTHER Study, which looked at neonatal outcomes in opioid-dependent pregnant women maintained on buprenorphine or methadone, Subutex (buprenorphine without naloxone) was found not only to be safe for pregnancy but to give better neonatal outcomes than methadone (Jones HE et al, NEJM 2010;363(24):2320–2331). In practice, the woman is usually switched over from Suboxone to Subutex as soon as she knows she’s pregnant. If a pregnant patient is already on methadone, it is prudent to continue methadone. Any detoxification or changes in medications are best done in the second trimester when the risk of pre-term labor or miscarriage are lowest, and in collaboration with the woman’s obstetrician. It is not uncommon for the dose of Subutex to increase slightly, especially in the third trimester. Pain management usually takes the form of epidurals during labor and full opioid agonists during the postpartum period.

According to the ASAM consensus statement, adolescent patients—those younger than 18 years old—appear to be at higher risk for complications from opioid addictions (overdose, HIV, suicide, death). In a study that randomized patients ages 15 to 21 to either 12 weeks of maintenance Suboxone or a Suboxone taper with discontinuation by day 14, those on maintenance Suboxone remained engaged in treatment longer. There are no studies that show what the physiologic side effects might be of maintaining adolescents on long term Suboxone. Nor do relatively short-term studies predict whether Suboxone will improve patients’ ability to stay clean over years. However, without engagement, all bets are off, and with potentially grave consequences. More research is needed and discussion should balance risks and benefits depending on the severity of the addiction.

Pain patients present a unique challenge. Sublingual buprenorphine is not FDA-approved for pain (although the IV form is). Use of buprenorphine for pain is considered off-label and does not count towards the 30- or 100-patient limit set by the DEA. Studies examining buprenorphine in humans and animal models show promise in the area of pain management. Buprenorphine may work synergistically with full agonists in current Suboxone patients going through an acute pain crisis (Kornfeld H and Manfredi L, Am J Ther 2010;17(5):523–528). Nevertheless, the ASAM consensus statement concludes that there is insufficient data to recommend the use of sublingual buprenorphine in the acute or chronic pain setting.

In medically complicated patients, buprenorphine may be better than methadone for patients with cardiopulmonary disease. It is less likely to cause respiratory depression due to its respiratory ceiling property. Buprenorphine is not contraindicated in patients with liver disease if enzymes are below three times the normal range, but there are no data on the use of buprenorphine in those with cirrhosis or liver failure. The use of Suboxone in these cases must again weigh the risks and benefits with the patient. The consensus statement reminds us to make sure our liver patients are vaccinated for hepatitis A and B as clinically appropriate.

Other Options for Opioid Addiction

Buprenorphine prescribers should also know there are other options worth considering. In addition to opioid-replacement therapies such as methadone and buprenorphine, there is also naltrexone—an opioid antagonist. Injectable (IM) naltrexone (Vivitrol) offers once a month dosing, shows some promise in studies and should be considered as an option for opioid addiction. Although expensive, many insurance companies will cover some or all of it (Bart G, J Addict Dis 2012;31(3):207–225).

TCPR’s Verdict: Buprenorphine is a powerful and effective medication. It is relatively safe in pregnancy and may prevent adolescent addicts from untimely death. It may gain widespread use in chronic pain management one day. However, there are hindrances for most who take it, given the monitoring and high medication costs that will not likely abate, not to mention the burdens upon the prescriber. It cannot be prescribed liberally, or in large quantities. But it’s becoming an essential part of the treatment of opioid dependence, and it can enable the transformational change that makes addiction treatment especially rewarding.