Opiates comprise a class of
substances derived from opium that includes illicit drugs, most notably heroin, and prescriptions drugs like codeine, Dilaudid, morphine, Demerol, and oxycodone. An estimated 123,000 Americans reported current heroin use in 2001. And, in recent years, abuse of prescription drugs has led to an increase in the numbers of patients who require treatment for opiate addiction.
Substituting a less addictive opiate for a more addictive one, and gradually tapering it over time, is a well-established technique for reducing the use of illicit opiates. Two currently available opiate-substitution therapies (also known as maintenance treatment) are methadone and levomethadyl acetate. But these are provided only in a strictly regulated environment in which medication is taken under clinical observation, which limits take-at-home dosing. And, access to such therapies, which often involves a long waiting list, is limited to persons with defined histories of documented, chronic opiate addiction; those with a relatively recent addiction are ineligible. Finding alternative medications that could be safely and conveniently administered in a physician’s office could potentially reach far more addicted individuals.
One proposed office-based treatment for opiate addiction is a tablet formulation of buprenorphine (an opioid derivative whose pain-relieving effect lasts longer than morphine) and naloxone (which can diminish the potential for abuse with buprenorphine). In a new study published in the September 4, 2003 issue of
The New England Journal of Medicine
, researchers tested buprenorphine and naloxone and found them to safely and effectively reduce the use of opiates and the cravings for opiates among opiate-addicted persons.
About the Study
The researchers conducted a two-part study at multiple sites: first, a four-week, double-blind, placebo-controlled, and second, an open-label safety phase (where both researchers and participants knew what drug the participants were taking and the dosage) lasting an additional 48 to 52 weeks.
During the four-week trial, participants were randomly assigned to daily treatment with buprenorphine alone (16 milligrams, or mg), buprenorphine (16 mg) in combination with naloxone (4 mg), or placebo. During the open-label phase, participants were given buprenorphine alone for two days after which they were given the combination tablet at increasing doses. After that, at the discretion of the investigators, up to a 10-day supply of medication could be provided for participants’ use at home.
Participants, enrolled between October 21, 1996 and September 30, 1997, were men and women between the ages of 18 and 59 years who met established criteria for opiate dependence and who were seeking opiate-substitution pharmacotherapy. Participants were excluded if they had any medical condition that made study participation medically hazardous.
All study visits took place in a physician’s office distinct from a clinic where methadone or levomethadyl were provided. Urine samples were collected during both phases of study to measure drug use. Participants’ cravings were assessed using a rating scale (where 0 represented “no craving” and 100 “the most intense craving I ever had”).
The first part of the trial was stopped early because buprenorphine and naloxone were found to work better than placebo. The researchers found both buprenorphine-based treatments significantly reduced opiate use; there was a 17.8% decrease in the presence of opiates found in urine tests in the combined-treatment group and a 20.7% decrease in the buprenorphine only group, as compared with a 5.8% drop in the placebo group. Both of the buprenorphine-based treatments also significantly reduced the craving for opiates.
With regard to the open-label part of the study, the researchers found that the overall rate of adverse events (such as headache, withdrawal symptoms, pain, insomnia, nausea, and sweating) did not differ significantly among groups. Thus, buprenorphine was well tolerated when given alone or in combination with naloxone. The percentage of opiate-negative urine samples ranged from 35.2% to 67.4% in multiple assessments.
How Does This Affect You?
This study showed that it is possible to administer buprenorphine or a combination of buprenorphine and naloxone in an office-based setting with good results. Both regimens were well tolerated and both reduced the craving for opioids and the use of opioids. The open-label phase of the study confirmed the safety of the buprenorphine-naloxone combination.
While the percentage of opiate-negative urine samples was significantly higher with either active treatment than with placebo, fewer than one-quarter of the urine samples in each of the treatment groups were free of opioids. However, the percentage of opiate-negative specimens improved greatly during the open-label phase—consistent with results seen for methadone or levomethadyl acetate in other studies.
Office-based therapy—which could be readily obtained without prior treatment, inconvenient clinic locations, or long waiting lists—will hopefully become the wave of the future for opiate addiction. The challenge now is to train physicians in the appropriate use of these agents in their existing practice settings. If you or someone you care for is dependent on opiates or any other drug, seek help from your doctor, a treatment center, or a support group in your area.
Fudala PJ, Bridge TP, Herbert S, et al. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.
Clark, HW. Office-based practice and opioid-use disorders.
Trends in Alcohol, Tobacco, and Other Drug Use and Treatment. Substance Abuse and Mental Health Services Administration (SAMHSA). Available at: http://samhsa_search.samhsa.gov/ Accessed September 2, 2003.
Please be aware that this information is provided to supplement the care
provided by your physician. It is neither intended nor implied to be a
substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER
IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the
advice of your physician or other qualified health provider prior to
starting any new treatment or with any questions you may have regarding a