Study explores challenge of initiating patient on injectable naltrexone

A placebo-controlled study that failed to demonstrate efficacy of a medication regimen for opioid detoxification nevertheless offered some promising news for programs seeking to help opioid-dependent patients initiate treatment with injectable naltrexone (Vivitrol).

Programs that offer medication-assisted treatment for opioid addiction often face the dual challenge of accommodating patients who prefer not to be on a maintenance drug (methadone or buprenorphine) but helping them to remain opioid-free for the week to 10 days necessary to be able to receive the opioid antagonist Vivitrol. Research supported by Vivitrol maker Alkermes, Inc., therefore tested the effectiveness of low doses of oral naltrexone with or without buprenorphine in a seven-day opioid detox protocol.

“We were hoping that adding those [medications] would make a difference, and maybe a manufacturer could then make these doses available in the market,” lead researcher Adam Bisaga, MD, research scientist at the New York State Psychiatric Institute who has conducted numerous medication treatment studies in addictions, tells Addiction Professional.

The study found, however, that the detox protocols involving oral naltrexone resulted in similar induction rates to Vivitrol as a protocol in which patients received placebo. Yet all of the study's detox protocols, delivered in an outpatient setting, were generally effective in transitioning patients to Vivitrol, and all were largely well-tolerated. The research findings were published last week in Drug and Alcohol Dependence.

“There were enough positive results that this was reassuring,” says Bisaga. “Very few people believed that you could do this on an outpatient basis.”

And here's what might have been the most striking finding of all: Even though many patients continued to use illicit opioids during the transition period to Vivitrol induction, “infrequent use of opioids did not seem to preclude patients from making a successful transition to [Vivitrol],” study authors wrote.

“If they use [opioids] once or twice and you give them the low doses of the withdrawal symptom meds, that's all they need,” Bisaga explains.

He believes the study's findings, while not making the case for market availability of the tested detox protocol, should hearten any treatment providers who have assumed that barriers to introducing a patient on Vivitrol treatment are insurmountable.

Details of study

Adult patients in the study had moderate to severe opioid use disorder, with consistent use of opioids (mainly heroin) for at least three months. All were instructed to discontinue all opioids for at least 12 hours prior to randomization to treatment.

A total of 378 patients were randomized to either seven days of oral naltrexone concurrent with a three-day sublingual buprenorphine taper, seven days of oral naltrexone coupled with placebo, or all placebo. The patients attended an outpatient clinic daily during the transition period leading up to Vivitrol initiation (where they received counseling and ancillary medications to assist in withdrawal). Those who met criteria for stable withdrawal received a first Vivitrol injection on day eight.

The researchers found that the percentage of patients receiving and tolerating the first dose of Vivitrol was comparable in all three groups, with both the naltrexone-buprenorphine and all placebo groups at 46%. Patients receiving naltrexone, either with or without buprenorphine, were more likely to remain abstinent from opioids during the transition period. No patient deaths occurred during the study, which had a follow-up period that extended for 13 weeks past randomization.

Study authors wrote, “It is worth noting that most of the treatment sited that took part in this multisite trial had no prior experience conducting outpatient opioid detoxification and [Vivitrol] induction; therefore, we believe that this protocol can be utilized in community-based treatment programs.”

But aren't methadone or buprenorphine inherently advantageous compared with Vivitrol, because a patient can initiate treatment immediately and without being completely opioid-free? Bisaga says in response, “Many patients are interested in non-opioid treatment. Do you give them no choice? You want to try to give people options.”