Naltrexone Implant Shows Promise for Polydrug Dependence

Deborah Brauser

March 05, 2012

March 5, 2012 — Treatment with naltrexone implants may result in decreased polydrug dependence, new research suggests.

In a randomized controlled trial of 100 patients addicted to both heroin and amphetamines, those receiving naltrexone implants showed significantly greater reductions in use of both substances, greater improvement scores on the Clinical Global Impressions (CGI) scale, and higher rates of study retention compared with their counterparts receiving placebo.

Investigators note that these results provide "the first evidence of an effective pharmacologic treatment for this type of polydrug dependence."

Still, lead author Jari Tiihonen, MD, PhD, professor in the Department of Clinical Neuroscience at Karolinska Institutet in Stockholm, Sweden, told Medscape Medical News that he was "not very surprised" by the findings.

Dr. Jari Tiihonen

"Previous studies have suggested that naltrexone might work in decreasing heroin or amphetamine use, although this had not been studied among subjects who were dependent on both drugs at the same time," said Dr. Tiihonen.

The study was published online February 17 in the American Journal of Psychiatry.

No Treatment for Polydrug Dependence

Commonly used to treat both alcohol and opioid dependence, naltrexone has also been shown to decrease amphetamine use. However, the investigators note that previous research suggests poor treatment adherence has rendered oral naltrexone ineffective for opioid addiction.

Other studies have shown that naltrexone implants are effective for heroin addiction but "the real-world effectiveness of long-acting naltrexone formulations is unknown" in those with polydrug addiction, report the researchers.

Dr. Tiihonen noted that drug dependence is a major worldwide issue, and although "the majority of drug addicts are polydrug dependent," no effective pharmacological treatment is currently available.

"Therefore, we wanted to study this topic. Having been working also as a forensic psychiatrist, I am interested in decreasing illicit drug use in order to decrease criminality," he added.

The study, which was conducted in Russia, included 100 treatment-seeking adults between the ages of 18 and 50 years with coexisting opioid and amphetamine dependence.

All participants were randomly assigned to receive either a naltrexone implant (n = 50; 92% men; mean age, 28 years; mean years of heroin addiction, 8.2; mean years of amphetamine addiction, 5.6) or a matching placebo implant (n = 50; 86% men; mean age, 29.3 years; mean years of heroin addiction, 8.7; mean years of amphetamine addiction, 5.6) for 10 weeks of treatment.

The primary outcomes measures included proportion of urine samples free of both drugs, clinical improvement as shown on the CGI, and retention in the study. Secondary measures included improvements on the Global Assessment of Functioning (GAF) scale.

Safety issues for all participants were monitored weekly.

More Research Needed

Results showed that 38% of the group receiving naltrexone implants had drug-free samples at the end of the 10-week study compared with 16% of the group receiving placebo (P = .01)

In addition, 56% of the naltrexone-treated group showed "much improvement" or "very much improvement" on the CGI vs just 14% of the placebo-treated group (P < .01).

The retention rate was also significantly higher for the patients treated with naltrexone than for those treated with placebo (52% vs 28%, respectively; P = .01), as were the mean GAF scores (82.0 vs 71.9, respectively; P = .004).

No significant between-group differences were found in cravings for either opioids or amphetamines.

Finally, no serious adverse events were found in any of the participants, although 2 of the naltrexone-treated patients reported "mild surgical side effects."

The investigators cited the relatively short 10-week treatment period as a possible study limitation, especially because polydrug dependence is considered a chronic disorder.

"It is likely that in clinical practice, patients should be treated with several successive implants in 2- to 3-month intervals to achieve long-term recovery from dependence," they write.

"Although long-acting naltrexone may be the first effective treatment for polydrug dependence, more research is needed to verify the generalizability of the results," added Dr. Tiihonen.

Not Available in the US

"This study was really well done," Walter Ling, MD, professor of psychiatry and director of the Integrated Substance Abuse Programs at the David Geffen School of Medicine at the University of California–Los Angeles, told Medscape Medical News.

Dr. Walter Ling

"However, it's important to note that it was done in Russia, and naltrexone implants are not available here in America. There are also cultural differences, so what we see there may or may not work out here," he said.

Dr. Ling, who was not involved with this research, added that "treatment options are very limited there" and that neither methadone nor bupropion are currently available in that country.

"When you do a study where there are limited choices of other treatments, it doesn't invalidate the findings. But it certainly affects the interpretation in the sense of how it applies to the community at large."

In 2010, as reported at the time by Medscape Medical News, results from a phase 3 randomized trial by Dr. Ling and colleagues were published in the Journal of the American Medical Association. In that study, the investigators found that buprenorphine implants were significantly more effective than placebo for reducing opioid use.

He reported that his investigative team is now conducting a study that is assessing the effectiveness of combining bupropion and naltrexone injections for treating cocaine use.

Overall, Dr. Ling commended Dr. Tiihonen and colleagues for investigating treatment for polydrug dependence.

"Up to now, it has been uncommon to treat 2 abuse drugs at the same time, even though that type of dependence is common. The investigators were focusing on just 2 drugs — heroin and amphetamines — but these are 2 very abused drugs, so this makes sense."

He added that these drugs have "very different characteristics. So it was an interesting combination to look at."

Nevertheless, "the context is the issue since naltrexone implants are available to them and not available here," said Dr. Ling.

"Still, it's something we should keep an eye on. And a study like this might be worth trying to repeat in our context with a different formulation of the medication."

The study was supported by the Finnish Ministry of Health and Social Affairs, the Finnish National Institute for Health and Welfare, and the Academy of Finland. The study authors have reported several financial relationships, which are listed in the original article. Dr. Ling has disclosed no relevant financial relationships.

AJP in Advance. Published online February 17, 2012. Abstract

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