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Outpatient Buprenorphine (suboxone) Treatment for Opioid Addiction  CME
Disclosures

John E. Franklin, MD, MSc  


Opioid addiction continues to be a vexing problem in the practice of medicine.[1] The relationship of opioid dependence and a variety of medical comorbidities is a major public health concern.[2] The continual drug-seeking behavior of patients with addiction to prescription drugs, such as oxycodone and hydrocodone, may be likened to that of heroin addicts.[3] Access to treatment has been problematic for many opioid-addicted individuals. There are only 180,000 methadone slots available for approximately 1 million individuals dependent on heroin.[4] Other barriers to treatment include stigma, cumbersome regulations, and lack of trained treatment personnel. Fortunately, 2 developments in 2003 should better address this problem. One is a proposal, still being considered, from the Bush Administration to increase the number of methadone voucher slots and the other is the US Food and Drug Administration (FDA) approval of buprenorphine for the treatment of opioid dependence.

Primary care physicians, in addition to addiction specialists, are the target care providers for buprenorphine treatment. Increasing access to treatment is a primary goal of buprenorphine treatment, and primary care physicians can play a big role in that process.

To that end, several buprenorphine training sessions have been conducted around the country to train primary care physicians in the use of buprenorphine. The National Medical Association (NMA), in conjunction with the American Academy of Addiction Psychiatrists (AAAP), conducted a training program in office-based buprenorphine treatment at the 2003 NMA Annual Convention and Scientific Assembly.[5]

The fact that buprenorphine can be prescribed by primary care physicians in the privacy of their offices is due to the Drug Addiction Treatment Act of 2000, according to John T. Picot, MD, a presenter at the NMA training session. The legislation allows buprenorphine, a schedule III medication, to be prescribed by qualified physicians in their offices. This is in contrast to methadone, which is a tightly regulated drug that can only be prescribed through licensed facilities. A qualified physician is one that has addiction certification by the AAAP, the American Society of Addiction Medicine, or the American Osteopathic Association or, most importantly, any licensed physician with a valid Drug Enforcement Agency (DEA) number who takes an 8-hour sanctioned training course, such as the one described here.

What is buprenorphine? As described by Dr. Pichot, it is a partial agonist at the mu-opioid receptor. How does it work in opioid detoxification and maintenance therapy? In contrast to a pure agonist, which is a drug that fully turns on a brain postsynaptic receptor, and an antagonist, which fully blocks a receptor, an opioid partial agonist, for example, tightly binds to the opioid receptor and only partially turns it on. At lower doses it can function as a weak agonist, but at higher doses the agonist effects reach a ceiling and it functions increasingly as an antagonist to other opioids that may try to latch on to the receptor.

What is the clinical advantage of a partial agonist in opioid dependence? Two dangers of exposure to pure agonists are overdose effects, most notably respiratory depression, and overstimulation of the brain's mesolimbic reinforcement system, which is the prime driver behind euphoria, craving, and loss of control seen in the addiction. When buprenorphine is prescribed to an individual physiologically dependent on opioids, it substitutes for the opioid of abuse and occupies opioid receptors. It minimizes withdrawal, with less danger of overdose or intoxication, because of its ceiling effect for euphoria and respiratory depression. Dr. Pichot presented a slide showing increased mu-opioid receptor binding potential on positron emission tomographic scans as buprenorphine dose was increased. At 16 mg, the receptors were completely saturated.

The clinical use of buprenorphine was described by John Franklin, MD, MSc, at the NMA training session. Buprenorphine can have 3 stages of use: induction, stabilization/maintenance, and withdrawal. The trick of induction or prescribing buprenorphine to someone who is physiologically dependent on an opioid, such as oxycodone, heroin, or methadone, is slowly titrating the buprenorphine dose. This is done to maximize its agonist and mild euphoric effects, while being careful not to kick off the pure opioid too quickly by its antagonist effects, which would precipitate severe withdrawal. Opioid addicts fear withdrawal, and most likely will discontinue use of the drug or mistrust you if you incorrectly induce buprenorphine.

Luckily, as Dr. Franklin describes, with a few pointers, buprenorphine is a relatively easy drug to administer. There are 2 preparations of the medication approved for opioid dependence in the United States. Both are sublingual preparations. The first is the trade name Suboxone, which is a 4-to-1 combination of buprenorphine and naloxone, a pure antagonist; the other is Subutex, which is pure buprenorphine.

What is the purpose of a combination tablet? Buprenorphine has been available in Europe for use in opioid addiction for several years, and there have been reports of addicts crushing the buprenorphine pills and shooting them intravenously in combination with benzodiazepines. This combination of intravenous buprenorphine and benzodiazepines has produced overdose deaths by synergistic effects on respiratory depression. To minimize this complication and decrease the illegal diversion of the drug, the FDA suggested the drug be used primarily as a combination product. The interesting property of the sublingual combination tablet is that naloxone is poorly absorbed sublingually but is fully active when injected. Thus, if an addict tries to boost a high by injecting Suboxone, the naloxone effect would precipitate an immediate, full-blown withdrawal syndrome.

So how do you start using the drug and what are the typical doses? Dr. Franklin describes that, on induction day, you typically want patients to come to your office in early opioid withdrawal, manifested, for example, by pupillary dilation, with mild symptoms of dysphoric mood, lacrimation, muscle ache, and diarrhea. Since the subjective experience of withdrawal is variable, you should ask about physical symptoms and observe signs to assure yourself that the patient is in some stage of early withdrawal. This is typically 12-24 hours after shorter-acting opioids, such as heroin, and 24 hours after longer-acting opioids. You can prescribe either Suboxone, 2 or 4 mg, or Subutex, 2 or 4 mg. You advise the patient beforehand that the first-day induction will require them to stay near your office for several hours. After initial dosing, the dose typically will have to be repeated at 2-hour intervals, up to a maximum daily dose of 8 mg the first day.

The next day, additional doses typically bring the patient up to 12-16 mg/d. At this point, the typical patient is starting to feel pretty good, not in withdrawal, not high. At this point, the experience can be pretty gratifying for both patient and physician. Once a maintenance daily dose is achieved, which can be anywhere from 8 to 24 mg, craving should be diminished. If addicts choose to use their opioid of choice, they would get minimal benefits or euphoria because of the antagonist effects of buprenorphine at that dose. Patients can be stabilized for a few weeks and then tapered off of the drug or they can continue taking the drug indefinitely, similar to methadone.[6] Withdrawal from buprenorphine is much easier and better tolerated than the withdrawal experienced with opioid agonists. Although buprenorphine could be tapered in 3-4 days, 3-4 weeks or longer is a more preferable taper.

If the medication is easy to use, is that it? Well, the answer is no. Drs. Pichot and Franklin and Dr. William Lawson, a copresenter at the NMA conference, spent the bulk of the training day highlighting other management considerations for the primary care physician who wants to prescribe office-based buprenorphine.[5] Even though you do not have to be an expert in addiction treatment to prescribe buprenorphine, physicians should be aware of the medical comorbidities typical in opioid addicts and manage them properly, and physicians should have a referral network for a range of psychosocial treatments for these patients. Hepatitis C, hepatitis B, HIV, and tuberculosis detection and management were highlighted by Dr. Franklin, in addition to the consideration of office setup, including training of office personnel and fee structure.

Dr. Pichot discussed the importance of patient selection in the success of buprenorphine treatment. Patients with totally unstable environments or resistance to psychosocial treatment, be it Alcoholics Anonymous, Narcotics Anonymous, or professional drug counselors or programs, are probably not good candidates for this form of treatment. Dr. Lawson highlighted the strong comorbidity of substance abuse and other psychiatric conditions: depression, bipolar disorder, posttraumatic stress disorders, personality disorders, and suicide. He stressed the need to actively address both the addiction and psychiatric disorders. Although there are causal associations between drug or alcohol use and psychiatric disorders, they need to be treated concurrently. Failure to adequately address comorbidities minimizes positive outcomes. Dr. Lawson also highlighted special considerations in the treatment of adolescents, pregnant women, geriatric patients, chronic pain, and ethnic minorities.

In summary, buprenorphine is an exciting new treatment for opioid addiction. Primary care physicians are being recruited to help increase the nation's treatment capacity. With a willingness to learn, brief training, and an adequate referral network, buprenorphine treatment can be a highly satisfying new treatment for physicians and patients, including patients addicted to prescription opioid medications.

References
Mack A, Franklin JE, Frances R. Concise Guide to Treatment of Alcoholism and Addictions. 2nd ed. Arlington, Va: American Psychiatric Publishing, Inc.; 2001.
Cherubin CE, Sapira JD. The medical complication of drug addiction and the medical assessment of the intravenous drug user: 25 years later. Ann Intern Med. 1993;119:1017-1028. Abstract
Mitka M. Abuse of prescription drugs: is a patient ailing or addicted? JAMA. 2000;283:1126, 1129.
Office of National Drug Control Policy. National Drug Control Strategy, 2000. Washington, DC: Government Printing Office; 2000.
Office-based buprenorphine treatment. Program and abstracts of the National Medical Association (NMA) 2003 Annual Convention and Scientific Assembly; August 2-7, 2003; Philadelphia, Pennsylvania.
Johnson RE, Chutuape MA, Strain EC, Walsh SL, Stitzer ML, Bigelow GE. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2000;343:1290-1297. Abstract

Hmmm my brower goes right to it/???

Thank you!

Is there another link? Thanks Fishmeal!