In October 2002 the Food and Drug Administration (FDA) approved Subutex and Suboxone for treatment of opioid addiction. These sublingually administered formulations of the partial opioid agonist buprenorphine were the first medications for opioid dependence since methadone and LAAM. The new drugs have been recognized as having the potential to transform the way opiate addiction is treated in the United States. Because our facility, Bowling Green Brandywine (BGB) in eastern Pennsyl-vania, has been a leader in the development of inpatient treatment strategies for opioid dependence, we clearly needed to investigate these new agents' implementation.
Subutex is the sublingual form of buprenorphine alone, while Suboxone consists of buprenorphine and naloxone in a 4:1 ratio. Naloxone, an opiate blocker, is added to eliminate potential for abuse of buprenorphine itself (i.e., by crushing and injecting it). Suboxone was developed for use in office-based outpatient treatment. Because we felt that BGB's highly structured residential environment would preclude abuse, we chose Subutex for our program. Both medications are available in 2 mg and 8 mg strengths and are marketed exclusively by Reckitt Benckiser Pharmaceu-ticals, Inc.
Buprenorphine acts as a partial agonist with high affinity and low intrinsic activity on certain opioid receptors (mu receptors). It acts as an antagonist, or blocker, on other receptors (kappa receptors).1 What this means for opiate-addicted patients in acute withdrawal is that, when given buprenorphine, they will experience relief of their withdrawal symptoms without the euphoria and sedation of a full opioid agonist such as methadone.
Buprenorphine has a mean half-life of 37 hours, allowing for once-daily dosing. Our review of the literature told us that patients who received this medication in the morning would not doze through the meetings and lectures that form the basis of our clinical program. Methadone's sedating effect when used as a detox medication is of particular concern in light of ever-shortening lengths of stay for treatment as dictated by insurers and funding sources. With many patients' inpatient treatment limited to detox only, patients who are sedated during their detox lose much of the benefit that counselors and group therapies have to offer.
Methadone tapers in use at BGB start at a level largely based on the patient's history of drug use (supported to an extent by the urine drug screen). Since drug histories provided by patients arriving for treatment are notoriously erratic, we set out to make treatment with Subutex more interactive. We hoped to develop treatment protocols determined by the patient's symptoms, not by the declared amount of opiates used (which tends to be exaggerated) or the values returned from the lab.
We recognized that since office-based buprenorphine administration (with the Suboxone formulation) could represent the future of opioid maintenance therapy, exposure to Subutex while at BGB could help our patients assess whether it works for them. We felt that the better informed patients were about this new medication, the more likely they could benefit from it.
To initiate the use of Subutex at BGB, we needed to identify a subset of the incoming opiate-addicted population that would be small enough to manage effectively in terms of induction and dosing, and be most likely to benefit from a Subutex detox. We designated two groups as candidates for Subutex: all patients in treatment for their first opiate detox, and those with a history of dependence on prescription opiates only. We also included any patients who specifically requested Subutex (they either had prior experience with the medication or simply had heard about it).
Because buprenorphine has a higher affinity for opioid receptors and because it is only a partial agonist, even without naloxone added it can precipitate acute withdrawal if given to patients who already have opiates in their system.2 Dosing guidelines published by Reckitt Benckiser therefore recommend induction in small, incremental doses.3 In keeping with the pharmaceutical com-pany's general recommendation, we required a minimum of eight hours since last use of heroin, 12 hours since last use of OxyContin, and 24 hours since last use of methadone.
Patients were screened for disqualifying medical conditions, advised of the medication's side effects, given a printout of information about the medication, and started on a 4 mg sublingual dose of Subutex. Initially patients were told to return to the nursing department anytime between two and six hours after their first dose if they experienced any withdrawal symptoms. This was later simplified to, “Come back in four hours so we can see how you are doing.” Patients who reported any symptoms of opiate withdrawal after four hours received another 4 mg of Subutex.
On day two a nurse evaluated patients prior to dosing, using a tool we developed called the Subutex Protocol Withdrawal Assessment. This tool recorded whether the patient had been given a second dose of Subutex on the previous day, and evaluated his/her general physical condition both subjectively and objectively. Patients were asked to record how they felt (“OK,” “not so great,” or “terrible”); any reported or observed withdrawal symptoms including nausea, vomiting, stomach cramps, chills, body aches, runny nose, anxiety, insomnia, and agitation were recorded. Most patients who had not received a second dose during the induction phase were automatically given 8 mg on day two. Patients who had received 8 mg of Subutex during the induction phase were given 10 mg on day two.