Buprenorphine effectively prolongs abstinence and prevents relapse in the
long-term maintenance treatment of heroin-dependent patients, researchers have
found in a randomized, placebo-controlled, double-blind clinical trial.
This study was funded by the National Institute on Drug Abuse (NIDA) and
conducted at an outpatient research clinic in Muar, Malaysia, between July
2003 and May 2004. The results were published in the June 27 The
After completing a two-week residential detoxification program at baseline,
126 patients with a DSM-IV diagnosis of heroin dependence were
randomly assigned to one of three arms of treatment—oral buprenorphine
(n=44), naltrexone (n=43), or placebo (n=39) for 24 weeks. Those treated with
buprenorphine had significantly longer duration of abstinence before the first
heroin use (positive urine test) and duration to heroin-related relapse (three
consecutive opioid-positive urine tests) than those who received naltrexone or
placebo (see FIG1). The
buprenorphine-treated group also had significantly better outcome than the
placebo group in the maximum number of consecutive days of abstinence.
All patients in the study also attended weekly sessions of individual and
group counseling, which included education and training on preventing relapse
and reducing risky behaviors linked with HIV transmission. All patients were
given urine drug tests three times a week.
The participants in each treatment group had been using heroin for an
average of 14.5 to 16.4 years. Three quarters or more of the participants in
each group had used injected drugs.
Retention is critical to the success of substance-dependence treatment. At
the end of the six months, 36, 29, and 23 patients in the buprenorphine,
naltrexone, and placebo groups, respectively, remained in the treatment. The
retention rate in the buprenorphine group was higher than either the
naltrexone or placebo group; however, the rate did not differ significantly
between the naltrexone and placebo groups.
"This is the first randomized study, to our knowledge, that directly
compares an [opioid receptor] agonist with the antagonist naltrexone,"
Richard Schottenfeld, M.D., a professor of psychiatry at Yale University
School of Medicine and the lead author of this study, commented to
Psychiatric News. He noted that the study revealed a consistent
pattern in all of the efficacy indicators: "The buprenorphine group did
the best, the placebo group the worst, and naltrexone in the
In Malaysia, injected heroin abuse and associated HIV transmission pose a
significant public health problem. This study was undertaken as a part of
NIDA's international collaborative program that supports research in regions
with drug-related HIV/AIDS epidemics.
The authors of the study examined the effects of these treatments on
self-reported HIV high-risk behaviors and found that these behaviors decreased
significantly from baseline in all three groups, and the difference was not
significant among the groups.
"Heroin addiction is a very big problem and a major driver of
HIV/AIDS epidemic in that region of the world," Schottenfeld said."
The government had been very resistant to medical treatment for drug
addiction until the 1990s." The past decade saw a gradual shift in the
attitude of authorities, from locking up addicts in jail and detoxification
facilities to long-term maintenance medical treatment for substance dependence
The authorities in Malaysia and many other countries have considered opioid
agonists, such as buprenorphine and methadone, as a substitute addiction
rather than an effective treatment.
"Stigma is what's underlying a lot of the resistance to agonist
maintenance treatment," according to Schottenfeld. He said the Malaysian
authorities were initially opposed to the use of any opioid agonist. However,
this research and other objective evidence of the effectiveness of
buprenorphine have had a significant influence on the public health policies
in Malaysia. Recently, the country expanded approved treatment options to
"The use of oral naltrexone is often an indicator of moral
disapproval of substitution treatments with opioid agonists because they
stabilize addicts rather than attempt to produce abstinence," wrote
University of Queensland's Wayne Hall, Ph.D., and Richard Mattick, Ph.D., in
an accompanying editorial. The two researchers, who work at the university's
School of Population Health, recommended that "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."
In the United States, buprenorphine with and without naltrexone is approved
to treat opioid dependence. However, the stigma of and barriers to opioid
agonist treatment remain in place in the United States as they do abroad,
Schottenfeld pointed out. "Agonist maintenance treatments aren't as
widely available as they should be. Many heroin-dependent patients do not have
access to effective buprenorphine or methadone treatment."
Treatment-oriented policies are gaining ground in some countries.
Schottenfeld noted that several similar NIDA research programs are currently
being conducted in China and Iran and that there is a shift in many countries
toward increased recognition of the need for long-term medical treatment for
substance dependence as for any other chronic diseases.
An abstract of "Maintenance Treatment With Buprenorphine and
Naltrexone for Heroin Dependence in Malaysia..." is posted at<www.thelancet.com/journals/lancet/article/PIIS014067360860954X/abstract>.▪