Opioid-dependent individuals are more likely to be able to transition to extended-release injection naltrexone (Vivitrol, Alkermes) if they undergo naltrexone-assisted detoxification than if they receive a buprenorphine-based regimen, results of a randomized trial show.
The trial, conducted in 150 dependent adults, demonstrated that naltrexone-assisted detoxification increased the likelihood of a successful transition to extended-release injection naltrexone (XR-naltrexone) by almost threefold compared with those given a buprenorphine taper.
The research was published online January 10 in the American Journal of Psychiatry.
"Currently, outpatient detoxification is usually attempted, if it is offered at all, with a decreasing buprenorphine taper," lead author Maria Sullivan, MD, PhD, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York City, told Medscape Medical News.
She noted that the low doses of oral naltrexone used in their study are not commercially available, but said their study findings support the development of a detoxification regimen of ascending doses of oral naltrexone for transitioning opioid-dependent patients seeking induction onto XR-naltrexone for the prevention of relapse.
"Oral naltrexone carries the important advantage that patients can transition directly to XR-naltrexone without a waiting period. Thus, this approach may be a promising detoxification alternative," she said.
Because the study employed a pragmatic, open-label study design, Dr Sullivan is confident that the outcomes can be readily translated to the real-world.
"Many healthcare providers have expressed that successfully managing opioid withdrawal symptoms in an outpatient setting can be challenging, and at present, there are no clear clinical guidelines on how to transition patients to nonagonist treatment," she said.
"An FDA [US Food and Drug Administration]–approved fixed-dosing regimen of oral naltrexone may enable clinicians to implement a detoxification regimen that has proven to be useful in transitioning patients from opioid dependence to XR-naltrexone."
She also believes that, with physician outpatient time limited, nurses can play an important role in assessing opioid withdrawal and encouraging patient adherence.
"In the current opioid epidemic, it is imperative to unlock the full potential of each of the effective opioid use disorder pharmacotherapies, and we believe that this detoxification and transition regimen will improve utilization of XR-naltrexone," she said.
Approached for comment, Thomas R. Kosten, MD, Jay H. Waggoner Chair and professor of psychiatry and neuroscience, Baylor College of Medicine, and research director, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, welcomed the findings.
"One would hope it could become the standard of care," Dr Kosten told Medscape Medical News, referring to naltrexone-assisted detoxification.
"For the company, certainly this would be a significant advantage, because the way that the FDA package insert is written right now, we're supposed to go 10 days from the last dose of an opiate before you use a dose of naltrexone, and that's just about impossible in the United States, because there's hardly any inpatient facilities where you can do this."
With regard to patients being placed on a regimen of injectable naltrexone, he described the situation as "pretty dismal right now."
"There are some settings in which this might be more feasible, the criminal justice system being the most obvious one, where you're supposedly opiate-free while you're in jail," he noted. "Since half the prisoners in the US are in jail because of drug charges, this has the tremendous potential for clearing out the horrible situation within our prison systems right now, where they are way overcrowded."
The optimal approach for transitioning opioid-dependent adults to XR-naltrexone and preventing relapse has not been established. In their study, the researchers randomly allocated 150 opioid-dependent adults in a 2:1 ratio of naltrexone-assisted or buprenorphine-assisted detoxification regimens, followed by an injection of XR-naltrexone.
Naltrexone-assisted detoxification consisted of a day of buprenorphine followed by increasing doses of naltrexone plus clonidine (multiple brands) and other adjunctive medications and XR-naltrexone on day 8. The buprenorphine regimen consisted of a 7-day buprenorphine taper followed by a 7-day washout period before starting XR-naltrexone.
Both treatments were complemented by twice-weekly individual therapy sessions that focused on motivational interviewing, relapse prevention, and cognitive-behavioral therapy, with an emphasis on medication adherence.
The overall mean age of the participants was 35.2 years, and the average severity of opioid use was equivalent to 8.3 heroin bags per day, or 287.9 mg/day of morphine equivalents. Ninety-eight patients were assigned to naltrexone-assisted detoxification, and 52 received the buprenorphine regimen.
Successful XR-naltrexone induction was achieved in 56.1% of naltrexone-assisted patients and in 32.7% of those in the buprenorphine group. Logistic regression indicated that naltrexone was associated with a 2.89 increased likelihood of successful induction vs buprenorphine (P = .010).
Notably, prescription opioid users were 3.76 times more likely to transition to XR-naltrexone than heroin users (P = .002).
Successful second XR-naltrexone injection at week 5 was achieved in 50.0% of patients in the naltrexone group and in 26.9% of those in the buprenorphine group. Logistic regression showed that a successful second XR-naltrexone injection was 2.78 times more likely with naltrexone-assisted than with buprenorphine-assisted detoxification (P = .012).
There was a significant difference in the likelihood of achieving a successful second XR-naltrexone injection for prescription opioid users than for heroin users, at a 2.31-fold increased likelihood (P = .040).
There was no significant difference in the proportion of patients reporting at least one adverse event between the two treatment groups, at 76.5% of those given buprenorphine and 55.6% of those assigned to the naltrexone group.
The researchers say that the results "support the feasibility" of naltrexone-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," they write.
Discussing the difference in success rates between heroin users and prescription opioid users, Dr Sullivan said: "Heroin dependence may be understood as a proxy for greater severity of opioid dependence, compared to prescription opioid dependence."
Dr Kosten agreed, saying in referene to heroin users: "They are, first off, sometimes more addicted.
"The other is that they are inherently less stable; you get more homeless people in that group, you get more people who used to be prescription opiate users and they have switched to heroin because they can't afford it anymore," he said.
"They tend to certainly be a sicker group, in the sense that there's all sorts of infectious diseases and other things associated with heroin use, particularly if you're injecting the heroin, but even when you're smoking it."
With regard to a variety of treatments, several factors contribute to a poorer prognosis for heroin users, Dr Kosten concluded. "The same thing is true for methadone maintenance [and] for buprenorphine maintenance, and so it's not surprising that it would be true of a rapid transition program for getting people off opiates and on to depo naltrexone."
The study was supported by grants to individual investigators from National Institute on Drug Abuse. Dr Sullivan received medication for this study through the Alkermes Investigator-Initiated Trial program while he was a fulltime faculty member at Columbia University. She participated in the design, initiation, and conduct of this study while at Columbia and in the data analysis and manuscript preparation after becoming an employee of Alkermes. Other authors have disclosed relationships with industry.
Am J Psychiatry. Published online January 10, 2017. Abstract
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Cite this: Naltrexone Detoxification Improves Opioid Transition - Medscape - Jan 31, 2017.