NEW YORK – Buprenorphine, particularly in combination with naloxone, offers a safe and effective approach to the office-based management of opiate addiction, Walter Ling, M.D., said at the annual conference of the Association for Research in Nervous and Mental Disease.
Buprenorphine represents “a treatment strategy and treatment philosophy” as well as a medication, and has the potential to “return the treatment of opiate addiction to the hands of physicians … for the first time in nearly a century,” said Dr. Ling, professor of psychiatry and director of the substance abuse program at the University of California, Los Angeles.
The clinical advantages of buprenorphine over opiate-replacement drugs like methadone reflect its pharmacologic properties. As a partial agonist of the μ-opiate receptor, the drug has both agonist- and antagonistlike actions, depending on concentration. The potential for dependence is low, and a ceiling effect creates a high safety profile. Tight receptor binding means a long duration of action, which slows the onset of abstinence and attenuates withdrawal symptoms.
Buprenorphine can be made even safer with the addition of the opiate antagonist naloxone in a sublingual preparation (commercially available as Suboxone). Buprenorphine is absorbed far more readily than naloxone in this form (70% vs. 10%), but the difference is lost if the combination is taken via another route.
“If injected, it will precipitate withdrawal,” Dr. Ling said at the meeting, cosponsored by the New York Academy of Medicine.
The sublingual formulation has little street value, discourages intravenous use, and allows for flexible dosing, he said.
Studies upon which the approval of buprenorphine was based showed that it is safe and effective relative to methadone and placebo. In those trials, drug-free urine samples increased in a dose-related manner, Dr. Ling said.
A trial of the buprenorphine-naloxone combination showed the feasibility of providing it for maintenance to detoxified, stabilized patients through the intended route of delivery via the private physician's office and community pharmacy. The retention rate was high. “Physicians and patients liked it,” he said.
Other research suggests the utility of buprenorphine-naloxone for detoxification in the inpatient or outpatient setting. In both cases, the drug was compared with clonidine, which is conventionally used in this application.
In the inpatient setting, 75% of patients who underwent detoxification assisted by buprenorphine-naloxone remained in the study and were drug free (as confirmed by urine samples) after 13 weeks, compared with 30% using clonidine.
In the outpatient application, 30% of buprenorphine-naloxone patients remained and had clean urine tests, compared with 5% with clonidine, he said.
The inpatient study indicated that it would be necessary to treat 3.4 times as many patients with clonidine than with buprenorphine-naloxone to achieve one successful detoxification. With outpatients, the ratio was 5.4:1, Dr. Ling said.