Recovering Heroin Addicts Fare Better on Opiate Maintenance Therapy
July 2, 2008 — Detoxified heroin addicts maintained on the opioid agonist buprenorphine (
Subutex, Reckitt Benckiser) waited more days before using heroin, had significantly longer stretches without using the drug, and had longer stretches before a full relapse of repeated drug use than those receiving the opioid antagonist naltrexone (
Duopharma; Bangi) or drug counseling only (placebo) in a randomized, double-blind, placebo-controlled trial.
The 24-week study, which is published in the June 28 issue of the
Lancet, enrolled 126 detoxified heroin-dependent patients from an outpatient research clinic in Malaysia. Patients were randomized to drug counseling and oral buprenorphine, oral naltrexone, or placebo.
Based on an interim analysis, enrollment was stopped after 70% of the planned sample size had been recruited because of superior outcomes in the group receiving buprenorphine maintenance therapy.
"The most important implication of the study findings is that opioid agonist maintenance treatment should be made widely available and accessible as a treatment for heroin or other opioid dependence," lead author Richard S. Schottenfeld, MD, from Yale University School of Medicine, in New Haven, Connecticut, told
Medscape Psychiatry.
Similar Results Expected with Buprenorphine-Naloxone
The study drugs were buprenorphine, supplied by the manufacturer, and naltrexone.
Maintenance treatment with naltrexone was approved in Malaysia in 1996. At the start of this study, Subutex, but not buprenorphine-naloxone (
Suboxone, Reckitt Benckiser), was registered in other countries and thus was approved for import into Malaysia, said Dr. Schottenfeld. Suboxone was approved in Malaysia in December 2007 and has now replaced Subutex. "We would anticipate similar results with Suboxone," he said.
Findings Likely Apply to Other Countries, Other Opiate Addictions "We think the findings are relevant to the United States and other countries," said Dr. Schottenfeld. In the United States, approval of buprenorphine for maintenance treatment of opioid dependence has greatly expanded the options and availability of maintenance treatment, but most opioid-dependent individuals still do not receive effective treatment, and many do not have access to buprenorphine or methadone maintenance treatment, he noted.
Compared with methadone, buprenorphine is less easily abused, poses a smaller risk of overdose, and can be prescribed in a doctor's office as opposed to a drug clinic, he said in a press release issued by Yale University.
In Russia, heroin addiction is a major public health problem and a leading cause of HIV transmission, but the country still does not permit maintenance treatment with buprenorphine or methadone, he added. "The study results make clear that we need to make treatment with buprenorphine or methadone more available here and abroad," he said.
"We think the findings probably also apply to people addicted to prescription opiates [painkillers such as oxycodone (
OxyContin, Purdue Pharma) or oxycodone and acetaminophen (
Percocet, Endo Pharmaceuticals)] as well as heroin," he continued. Some of these individuals might also respond favorably to medically supervised withdrawal and treatment with naltrexone, he added, noting that newer, longer-acting, injectable naltrexone is being investigated for this use.
Direct-Comparison Study
Heroin detoxification followed by drug counseling or referral to self-help groups is a common treatment approach, despite little strong evidence for this and no studies directly comparing maintenance treatment with buprenorphine vs naltrexone, the group writes.
The scientists from Yale and from Muar, Malaysia undertook to perform a randomized, double-blind, placebo-controlled trial to compare these 2 agents and drug counseling only.
A total of 126 heroin-dependent patients who were recruited from the community in Muar and completed a 14-day detoxification protocol were randomly assigned to 1 of 3 treatment arms. The subjects were all males; on average, they were in their late 30s and had been addicted to heroin for about 15 years.
Each group received 24 weeks of manual-guided group and individual drug counseling plus buprenorphine (n = 44), naltrexone (n = 43), or placebo (n = 39).
The subjects had urine tests done 3 times a week to detect opiates, and the primary outcomes, over a 24-week period, were:
- Days to first heroin use.
- Days to heroin relapse (3 consecutive opiate-positive urine tests).
- Maximum consecutive days of heroin abstinence.
- Reductions in self-reported HIV risk behavior.
Best Results With Buprenorphine
There were significant overall differences between treatment groups for days to first heroin use, days to heroin relapse, and maximum consecutive days of heroin abstinence. Time to first heroin use was significantly greater with buprenorphine treatment than with naltrexone treatment. Days to relapse and maximum abstinent days were greater, but not significantly greater, with buprenorphine compared with naltrexone.
Outcomes on Maintenance Therapy Following Heroin Detoxification, Buprenorphine vs Naltrexone vs Placebo | Days | Buprenorphine, n = 44 | Naltrexone, n = 43 | Placebo, n = 39 | P* |
| In treatment | 117 (102 - 132) | 84 (64 - 103) | 70 (54 - 87) | .0002 |
| To first heroin use | 51 (33 - 68) | 24 (11 - 37) | 18 (8 - 28) | .0013 |
| To heroin relapse | 79 (61 - 98) | 64 (44 - 84) | 39 (25 - 53) | .0016 |
| Maximum consecutive heroin abstinence | 59 (43 - 76) | 42 (28 - 57) | 24 (13 - 35) | .0007 |
Days are mean (95% CI). All groups received drug counseling.
*Overall contrast for the 3 groups. HIV risk behaviors were significantly reduced from baseline across all treatment groups, but the differences were not significant between groups.
There is still room for improvement, since only two-fifths of patients remained in treatment, and only a quarter continued to receive treatment and avoid relapse throughout the 24-week treatment period, the group notes.
"Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public health approach to reduce the problems associated with heroin dependance," the group concludes.
Improving Treatment Adherence With the availability of Suboxone, patients can be prescribed this medication for self-administration outside of a clinic, which might improve treatment adherence, since the current study required that patients attend a clinic 3 times a week for supervised drug administration, Dr. Schottenfeld told
Medscape Psychiatry. Treatment adherence might also be enhanced with improved counseling and as heroin addicts learn that there is a high likelihood of relapse following premature discontinuation of maintenance treatment, he added. "Many heroin addicts believed that treatment 'cured' their addiction and that consequently they did not need to remain in maintenance treatment to continue to obtain the benefits of treatment," he noted.
Editorial: Treatment of Choice is Oral Substitution The sample size in the study by Schottenfeld and colleagues was large enough to show the superiority of oral buprenorphine over oral naltrexone, Wayne D. Hall, PhD, from the University of Queensland, in Australia, and Richard Mattick, PhD, from the University of New South Wales, in Sydney, Australia, write in an accompanying editorial.
"Prudent health authorities in developing countries should no longer restrict pharmacological treatment of opioid dependence to oral naltrexone....The preferred oral pharmacological treatment for opioid dependence should be agonist maintenance with either methadone or buprenorphine," they state.
Article Source:
Medscape.com Posted By:
Dee
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