If recent findings are validated in future studies, a novel, six-month treatment for opioid dependence with buprenorphine implants is poised to make a strong entrance into the armamentarium of medication-assisted therapy for addiction. In a randomized, placebo-controlled trial, subjects with opioid dependence who received buprenorphine implants used fewer opioids over 16 weeks than those who received placebo implants. Buprenorphine implant recipients also had significantly more opioid-negative urine tests over the entire six-month treatment period than those receiving placebo implants.
The implantable formulation was developed to address the problem opioid-dependent participants experience adhering to treatment with sublingual buprenorphine. The implants deliver an initial pulse of the drug followed by a constant, low-level release over six months, allowing recipients to avoid the plasma peaks and troughs often associated with sublingual buprenorphine, which can lead to cravings and relapses.
“It is likely that, in general, implantable buprenorphine will make it easier to manage opioid-dependent patients,” said Nora Volkow, MD, director of the National Institute on Drug Abuse, National Institutes of Health in Bethesda, Md.
The investigators conducted the six-month trial at 18 sites in the United States between April 2007 and June 2008. They randomly assigned 163 opioid-dependent patients, aged 18 to 65 years, to receive buprenorphine implants or placebo implants. Patients were excluded if they tested positive for AIDS, were dependent on psychoactive substances other than opioids or nicotine, used nonprescribed benzodiazepines, had received medication for opioid dependence within the previous 90 days, had chronic pain requiring opioid treatment or showed signs of impaired liver function.
After induction, in which all patients received a fixed dose of 12 to 16 mg of sublingual buprenorphine-naloxone tablets daily for at least three consecutive days, participants were randomized to receive either four implants of 80 mg buprenorphine each or four placebo implants. Patients with breakthrough opioid withdrawal or craving symptoms were given rescue doses of sublingual buprenorphine-naloxone as clinically indicated. Those who required supplementary tablets for three or more days in a week qualified to receive an additional implant. All subjects also received regular individualized drug counseling. Participants who needed further sublingual medication following administration of a fifth implant were considered treatment failures and withdrawn from the study.
During the six-month trial, the researchers collected urine samples three times weekly to determine the extent of opioid use, and found that a mean of 36.6% of the 72 urine samples collected from each participant were opiate-negative in the buprenorphine population compared with 22.4% of opiate-negative urine samples among placebo subjects. Furthermore, significantly more patients who received buprenorphine implants completed the study (65.7% and 30.9%, respectively).
The researchers also reported that buprenorphine implants were well tolerated, with a low rate of serious adverse events occurring in both treatment groups. Those who received buprenorphine implants had fewer clinician-rated and patient-rated withdrawal symptoms, had fewer patient-rated cravings and experienced a greater change on clinician global ratings of opioid dependence severity than those who received placebo implants.
The most common side effects were implant site reactions, which occurred in 56.5% of the buprenorphine group and 52.7% of the placebo group. These reactions included erythema, edema, itching, pain and bleeding.
According to lead study investigator Walter Ling, MD, three other six-month trials of sublingual buprenorphine showed retention rates ranged between 35% and 38% in similar treatment populations. Dr. Ling suggested that a higher buprenorphine dose may further increase the treatment’s efficacy.
“Given the known pharmacokinetics of buprenorphine, the steady-state plasma concentration levels are consistent with a constant buprenorphine release of 1 to 1.3 mg per day from four to five buprenorphine implants,” noted Dr. Ling, professor of psychiatry and director of the Integrated Substance Abuse Program in the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California, Los Angeles. “Extrapolating from this, it is possible that a higher number of implants would result in greater efficacy. However, since none of the patients in the treatment group met treatment failure criteria, it appears four or five implants sufficiently control most cravings and withdrawal symptoms.”
According to Dr. Volkow, several features make implantable buprenorphine more desirable than the sublingual drug. These include a lower risk for diversion and fewer clinic visits for patients. The study’s investigators excluded chronic pain patients and all subjects received behavior-based treatments, which makes it tough to generalize the study’s outcomes, she said.
“It’s difficult to say how patients would have fared if behavioral interventions weren’t part of the treatment protocol,” said Dr. Volkow, who was not involved in the study. “The next step in studying its efficacy is to compare treatment retention and abstinence rates with the implants to those seen with immediate-release buprenorphine.”
by David Wild
Dear Drugs-Forum readers: We are a small non-profit that runs one of the most read drug information & addiction help websites in the world. We serve over 4 million readers per month, and have costs like all popular websites: servers, hosting, licenses and software. To protect our independence we do not run ads. We take no government funds. We run on donations which average $25. If everyone reading this would donate $5 then this fund raiser would be done in an hour. If Drugs-Forum is useful to you, take one minute to keep it online another year by donating whatever you can today. Donations are currently not sufficient to pay our bills and keep the site up. Your help is most welcome. Thank you.
Buprenorphine Implants May Boost Treatment Retention Rates