Low-Dose Naltrexone May Mitigate Severity of Opioid Withdrawal During Detox

In 2010, the Food and Drug Administration approved a once-monthly extended-release injectable form of naltrexone (XR-naltrexone) for relapse prevention following opioid detoxification. However, before patients can be administered XR-naltrexone, it is recommended they first abstain from opioids for up to 10 days—a factor that some experts argue creates a significant barrier to its use.

A study published January 10 in AJP in Advance found that patients undergoing a rapid naltrexone-assisted detoxification were significantly more likely to successfully initiate XR-naltrexone than those undergoing a standard buprenorphine-assisted detoxification.

“By circumventing the need for a protracted period of abstinence and mitigating the severity of withdrawal symptoms experienced during detoxification, this strategy has the potential to considerably increase patient acceptability of, and access to, antagonist therapy,” Maria Sullivan, M.D., Ph.D., and colleagues wrote.

The researchers randomly assigned 150 patients seeking treatment for heroin or prescription opioid dependence to one of two outpatient detoxification regimens: naltrexone-assisted detoxification or buprenorphine-assisted detoxification.

As the authors described in AJP, “Naltrexone-assisted detoxification lasted seven days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications” to alleviate residual withdrawal symptoms. In contrast, “[b]uprenorphine-assisted detoxification included a seven-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone.” Patients in both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone at week 5.

Compared with those in the buprenorphine-assisted detoxification group, participants assigned to naltrexone-assisted detoxification were significantly more likely to receive XR-naltrexone (56.1 percent compared with 32.7 percent) and receive the second injection at week 5 (50.0 percent compared with 26.9 percent).

A secondary analysis found that prescription opioid users were significantly more likely to receive first and second injections of XR-naltrexone than patients using heroin.

“The most important clinical lesson from this study is that induction onto XR-naltrexone is feasible in an office setting,” Sullivan, an associate professor of psychiatry at the Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute, told Psychiatric News.  “[P]atients receiving oral naltrexone were just as comfortable as those receiving decreasing doses of buprenorphine.”

According to Sullivan, oral naltrexone in ascending doses provides gradual antagonism of opioid receptors and allows immediate transition to another opioid antagonist, XR-naltrexone. In contrast, it requires more time for buprenorphine—an opioid agonist—to be cleared from opioid receptors before transitioning XR-naltrexone.

Petros Levounis, M.D., M.A., a professor and chair of the Department of Psychiatry at Rutgers New Jersey Medical School, cautioned the findings leave many questions left unanswered about the role of naltrexone and buprenorphine in opioid detoxification—as both medications were associated with high rates of attrition.

“[The study] did not attempt to address opioid detoxification with naltrexone versus buprenorphine in general, or shed light into the important question of whether a partial agonist or an antagonist is a better choice in the treatment of opioid use disorder,” he told Psychiatric News.

Although Sullivan acknowledged more research into the effectiveness of these approaches is needed, she emphasized that “individuals seeking treatment for opioid use disorder deserve to be offered a fully informed choice of all three FDA-approved pharmacotherapies for opioid dependence [including methadone, buprenorphine, and naltrexone].”

She continued, “We hope that this study will increase patients’ access to MAT [medication-assisted treatment] by providing clinical guidance for practitioners on a method for successfully transitioning opioid-dependent individuals to XR-naltrexone in an outpatient context.”

The study was funded by the National Institute on Drug Abuse. ■

An abstract of “Long-Acting Injectable Naltrexone Induction: A Randomized Trial of Out-patient Opioid Detoxification With Naltrexone Versus Buprenorphine” can be accessed here.