Naltrexone, Buprenorphine Combination Effective for Opioid Abstention Patients

Adam Bisaga, MD

Low-dose oral naltrexone (NTX), either as a single therapy or in combination with brief buprenorphine (BUP) taper, has been proven capable of managing opioid withdrawal symptoms in patients abstaining from the drugs prior to beginning injectable extended-release naltrexone (XR-NTX) for opioid use disorder (OUD).

Sub-analysis results from the study, presented at the American Society of Addiction Medicine conference Friday, found reason to believe such a detoxification protocol could improve rates of patients that follow through with OUD therapy.

Adam Bisaga, MD, professor of Psychiatry at the Columbia University College of Physicians and Surgeons, NY, told MD Magazine that there hasn’t been a proven effective method to get patients through the US Food and Drug Administration (FDA)-mandated detoxification stage towards therapies.

“Only 10-20% come back after their first visit to begin therapy,” Bisaga said. “They want to do the therapy, but can’t get through the abstinence stage.”

Researchers compared 3 therapy arms for their efficacy of getting patients OUD to pass a naloxone challenge prior to XR-NTX therapy after 8 days. They randomized 378 patients onto either NTX plus brief BUP taper; NTX plus placebo BUP taper; and both placebo NTX and BUP taper.

Patients received 7 days of ascending NTX or placebo, concurrent with a 3-day BUP or placebo taper, as well as ancillary therapies, all from an outpatient setting. Bisaga added that optional daily psychiatric counseling was made available for the patients. Following the 7-day regimen, patients were administered a naloxone challenge to gauge whether they could begin receiving XR-NTX.

Compared with the placebo NTX and placebo BUP combination group, the NTX/BUP group demonstrated a greater opioid abstinence rate during the treatment period, as well as lower post-XR-NTX subjective opioid withdrawal scores.

However, the transition rates to XR-NTX were comparable across all groups. NTX/BUP patients reported a 46% rate; NTX plus placebo BUP reported 40.5%; Placebo NTX plus placebo BUP reported 46%.

Though the trial did not reach its primary endpoint, adverse events (AEs) were reported in less than one-third (32.5%) of all patients, with mild-to-moderate AEs consistent with opioid withdrawal being most commonly reported. Bisaga added that were no reported patient deaths during the trial — a success in the scope of an epidemic that costed roughly 40,000 US lives due to overdose in 2016 alone.

Researchers added that finding multiple well-tolerated and efficacious detoxification and induction regimens is encouraging for clinicians considering the XR-NTX therapy.

“Moreover, the fact that outpatient induction onto XR- NTX was associated with only mild opioid withdrawal, and that both objective and subjective measures of withdrawal, together with cravings for opioids, declined steadily throughout the transition period, should be reassuring to providers and patients concerned that detoxification may be associated with significant discomfort,” researchers wrote.

XR-NTX was first approved for the prevention of relapse to opioid dependence by the FDA in 2010. Though it’s associated with increased treatment retention, decreased relapse, and decreased cravings for opioids in both outpatient and inpatient settings, it also requires patients are not physiologically dependent on opioids prior to administration. As a result, patients in an outpatient setting are at a particular disadvantage of beginning the therapy.

Research into properly detoxifying patients with OUD has been circulating for decades, Bisaga said, with a new iteration of research reaching the public every 5 or so years. This most recent iteration — finding that the process is feasible across multiple measures — has an affirming tone.

“Physicians can use this data to build their own protocols,” Bisaga said.

Sub-analysis of data from the study, "Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial," was presented at the American Society of Addiction Medicine meeting on April 13.