PARIS – Patients recovering from opioid dependence who received monthly injections of 380 mg of extended-release naltrexone reported significant improvements in weeks of abstinence, cravings, and opioid-free days, compared with a placebo group. The findings were published in the Lancet (2011; 377:1506-13) and subsequently presented at the annual meeting of the European Congress of Neuropsychopharmacology.
Naltrexone, an opioid receptor antagonist, has been used to support recovery in opioid-addicted patients, but adherence to the oral medication tends to be poor, which limits effectiveness, said Dr. Evgeny M. Krupitsky of St. Petersburg State Pavlov Medical University, Russia, and his colleagues.
A once-monthly, extended-release naltrexone (XR-NTX) injection has been approved in Russia and in the United States to treat alcohol dependence. Dr. Krupitsky and his colleagues conducted a randomized, placebo-controlled trial to test the safety and effectiveness of the injectable drug in patients with opioid dependence.
The study population included 250 patients aged 18 years and older who were within 30 days or less of completing an inpatient opioid detoxification program. The majority of the patients were young, white men who had been suffering from heroin addiction for about 10 years. Patients were excluded if they were on parole or probation, were pregnant or breastfeeding, or had significant medical conditions such as renal failure, hepatic failure, or histories of AIDS-indicator disease.
Patients were randomized to 380 mg XR-NTX or placebo starting within 1 week after completing detoxification and continuing with one injection every 4 weeks, for a total of six injections over a 24-week period. Patients also were offered counseling sessions.
"XR-NTX offers a new treatment option without the risk of physical dependence or illegal diversion."
After 24 weeks, the median proportion of weeks of confirmed abstinence (the primary end point, based on urine tests) was significantly higher in the treatment group, compared with the placebo group (90% vs. 35%). This translated to 45 patients with confirmed abstinence in the treatment group, compared with 28 patients in the placebo group.
The median retention rate was more than 168 days in the treatment group, compared with 96 days in the placebo group. Relapses were confirmed in 17 placebo patients and 1 XR-NTX patient using a naloxone challenge.
In addition, the mean change in cravings, compared with baseline, was significantly greater in the XR-NTX group, compared with the placebo group (–10.1 vs. 0.7) and significantly more patients in the XR-NTX group reported opioid-free days, compared with the placebo group (99% vs. 60%).
Overall, 63 of the XR-NTX patients (50%) and 40 of the placebo patients (32%) experienced at least one adverse event, the most common of which were nasopharyngitis and insomnia.
Two patients in each group discontinued the study because of adverse events, but none of the XR-NTX patients died, overdosed, or discontinued treatment because of severe adverse events. Three patients in the XR-NTX group reported four serious adverse events, including infectious processes such as AIDS or HIV. Four patients in the placebo group reported five serious adverse events, including infections, psychotic disorder, and a peptic ulcer.
The study was limited by a lack of comparison with oral naltrexone, but other studies comparing oral naltrexone with placebo have failed to show an effect on craving reduction or relapse prevention, the researchers noted.
"The extent of patient interest in XR-NTX when opioid substitution treatments are available remains a topic for future health services research," the investigators said. However, "XR-NTX offers a new treatment option without the risk of physical dependence or illegal diversion," and the injectable treatment approach might improve acceptance of pharmacotherapy for opioid addiction, they said.
The study was funded by Alkermes. Dr. Krupitsky had no financial conflicts to disclose.