generally well tolerated and beat out placebo in reducing opioid use and decreasing opioid cravings in opioid-dependent patients, new research suggests. After 24 weeks, the median percentage of opioid-free urine screens was 90% among patients taking extended-release naltrexone, compared with 35% among patients taking placebo (P < .0002).
David R. Gastfriend, MD, vice president of scientific communications for Alkermes, presented the results of the 250-patient, double-blind, placebo-controlled, phase 3 study here at the American Psychiatric Association (APA) 2010 Annual Meeting.
„Despite currently available treatments, more than half of the 1.3 million Americans suffering from [opioid dependence] remain untreated, and the global disease burden is growing. Extended-release naltrexone appears to offer an important alternative treatment strategy that addresses the obstacle of poor patient adherence,“ Dr. Gastfriend said.
„The number of Americans addicted to prescription opioids and heroin has more than doubled since 2000. What’s driving this increase? About 20% is attributable to heroin. The much larger problem is addiction to prescription drugs,“ he told Medscape Psychiatry.
Less Potential for Addiction
Extended-release naltrexone was approved by the US Food and Drug Administration (FDA) for treating alcohol dependence in adults who have completed detoxification treatment in 2006. The FDA recently designated the company’s supplemental new drug application for extended-release naltrexone for opioid addiction as a priority review, Dr. Gastfriend said.
Opioid addiction is typically treated with substitution therapy, typically with methadone or buprenorphine, „agonist medications that bind to opioid receptors and mimic the drug’s effects,“ he said.
This approach carries a host of problems, including access, acceptability, diversion, illicit use, and overdose deaths, he added.
In contrast, naltrexone, including the oral formulation, is an opioid antagonist, preventing opioids from binding to receptor sites. As a result, there is less potential for addiction, he said.
„The once-monthly formulation addresses the added obstacle of adherence,“ said Dr. Gastfriend.
Detox Before Treatment
For the study, 250 patients with opioid dependence recruited from 13 sites in Russia from July 2008 to October 2009 were randomized to 24 weeks of treatment with 380 mg of extended-release naltrexone by intramuscular injection (n = 126) or placebo injection (n = 124), every 4 weeks.
„Patients must be detoxed fully before treatment,“ Dr. Gastfriend said. In this study, patients had not been taking any opioids for 7 to 30 days, and the first dose was administered within 1 week of inpatient discharge.
All patients received biweekly individual drug counseling. No significant differences were found between the treatment groups in demographic or baseline clinical characteristics.
The mean age of patients was 29.4 and 29.7 years in the naltrexone and placebo groups, respectively. A total of 89.7% and 86.3% of patients in the naltrexone and placebo groups were male, and their mean duration of opioid dependence was 9.1 and 10.0 years, respectively. Most (88.1% in the naltrexone group and 88.7% in the placebo group) were addicted to heroin.
The primary endpoint was the response profile based on the rate of opioid-free urine test results from weeks 5 to 24.
In addition to their significantly better median percentage of opioid-free drug screens, patients taking naltrexone fared better on a number of secondary endpoints.
Total abstinence (100% opioid-free weeks) was reported in 45 (35.7%) of treated patients vs 28 (22.6%) of placebo recipients (P = .02).
The median number of days receiving treatment was more than 168 for naltrexone-treated patients vs 96 in the placebo group (P = .004).
Also, significantly more naltrexone-treated patients completed the study: 53.2% vs 37.9% (P = .017). None of the patients in the naltrexone group discontinued treatment because of adverse events; 22 (17.5%) dropped out because of lack of efficacy.
In addition, naltrexone-treated patients showed a 50% mean reduction in cravings from baseline on the visual analog scale craving score, compared with no change for placebo-treated patients (P < .001).
„The placebo group never goes below baseline and bumps up as they leave the study. For the naltrexone group, cravings decreased in the first week, progressively decreased through the eighth week, and [were] significantly different from baseline every week until the end of study,“ Dr. Gastfriend said.
No significant difference was seen in the incidence of clinical adverse events between the groups.
The most common clinical adverse events were nasopharyngitis, seen in 7.1% of naltrexone-treated patients, and insomnia, in 6.3%.
Asked if the drug would be compared against existing treatments for opioid dependence rather than placebo, Dr. Gastfriend said such a study night be difficult to design, in part because of patient preferences.
Extended-release naltrexone „is not intended to take over existing treatments; it’s another tool in the armamentarium,“ he said.
Opioid Dependence Drugs Underused
Commenting on the findings, Petros Levounis, MD, director of the Addiction Institute of New York at St. Luke’s and Roosevelt Hospitals, in Manhattan, said, „It’s encouraging news to have more options in our treatment of opioid dependence.
„But the issue we need to look at is the issue of compliance. How many people…are willing to have shot every month? That’s the idea in my mind. Some people prefer the pill once a day; some would rather have the shot once,“ he said.
He agreed with Dr. Gastfriend that an advantage over agonist medications is that „you certainly have a risk of physical dependence, even addiction at times, with them.“
Dr. Levounis said that in the United States, pharmacologic treatment for opioid dependence is vastly underused.
„The majority of detox centers give people a referral to an outpatient treatment program, sometimes to inpatient rehab. But very rarely do they give them recommendations for medications like these.
„Oral naltrexone and buprenorphine haven’t caught on. That’s [partially] because of physician awareness, [partially] because of tradition, or momentum, if you like. There’s difficulty with reimbursement at times.
„More than anything it’s the culture of detox units. They dictate a nonpharmacology trajectory. They say just come here, we’ll take you off the drugs, and then you go out and should be able [to handle yourself].
„It’s really a shame [that we don’t use pharmacologic interventions as often as we could]. There are a lot of addictions that we don’t have good meds for…but for some, like opioids, we’ve come up with some particularly good medications, and we should use them,“ Dr. Levounis said.
The study was funded by Alkermes Inc. Dr. Gastfriend is an employee of the company. Dr. Levounis has disclosed no relevant financial relationships.
American Psychiatric Association (APA) 2010 Annual Meeting: Abstract NR7-06. Presented May 26, 2010.