MedicalResearch.com Interview with:
Maria Sullivan, M.D., Ph.D
Senior Medical Director of Clinical Research and Development
MedicalResearch.com: What is the background for this study?
Response: Extended release injectable naltrexone is approved for the prevention of relapse to opioid dependence after detoxification and when used with counseling. It is recommended that patients abstain from opioids for a minimum of seven to 10 days prior to induction onto XR-naltrexone to avoid precipitating opioid withdrawal. This requirement of detoxification represents a substantial clinical challenge, particularly in the outpatient setting.
There is currently no single recognized best method for opioid detoxification prior to first dose of extended-release naltrexone (XR-naltrexone). A number of induction regimens have been explored, including the use of low doses of oral naltrexone to shorten the transition period from dependence on opioids to XR-naltrexone treatment. The goal of the study was to help establish an outpatient regimen to transition subjects from physiological opioid dependence to XR-naltrexone treatment and mitigate the severity of opioid withdrawal symptoms.
We hypothesized that low-dose oral naltrexone, combined with buprenorphine and psychoeducational counseling, would assist with the transition of patients with opioid use disorder onto XR-naltrexone. In this 3-arm trial, we examined the utility of oral naltrexone, buprenorphine, and a fixed regimen of ancillary medications (oral naltrexone + buprenorphine vs. oral naltrexone + placebo buprenorphine vs. placebo +placebo), to determine whether any of these regimens was associated with higher rates of induction onto XR-naltrexone.
MedicalResearch.com: What are the main findings?
Response: The rate of transition to XR-naltrexone was similar in all three treatment arms, or induction protocols. Thus, the study did not meet its primary endpoint of demonstrating that the addition of low dose oral naltrexone, with or without buprenorphine, would improve the success rate of initiating treatment with XR-naltrexone.
Secondary findings included the observations that, as participants progressed through the outpatient detoxification and induction, they experienced progressively fewer withdrawal symptoms and craving scores throughout the week, as measured both subjectively and by the clinician across all treatment arms.
MedicalResearch.com: What should readers take away from your report?
Response: The safety and opioid withdrawal data demonstrated that all three tested regimens were generally well-tolerated by patients inducted onto XR-naltrexone. Most adverse events were of mild to moderate severity and consistent with symptoms of opioid withdrawal. The fixed dose ancillary medication regimen, and the eight-day duration of transition period employed in the study, permitted daily management of opioid withdrawal and the induction of XR-naltrexone in an outpatient setting. Daily contact by the physician or health care practitioner with the patient during detoxification, to monitor for withdrawal symptoms, is believed to be important.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: This study found that in a seven-day regimen, the use of oral naltrexone, with or without buprenorphine, did not result in higher rates of transition to XR-naltrexone in an outpatient setting, compared to the use of placebo and a standing regimen of ancillary medications. But we did observe that participants in the two treatment arms which included oral naltrexone had significantly higher abstinence rates during the induction process. Research efforts could investigate whether patients who receive oral naltrexone during detoxification are able to pass a naloxone challenge, and receive XR-naltrexone treatment for prevention of relapse to opioid dependence, earlier in the detoxification process than patients who do not receive oral naltrexone We also observed that 57% (n=51/89) of study participants who passed a naloxone challenge and were successfully inducted onto XR-naltrexone on Day eight had an opioid-positive urine drug test result on the day of induction. Further research could provide understanding of the limits and implications of brief lapses to opioid use, suggested by these data, when transitioning patients to XR-naltrexone. Future studies could also help to inform procedures for the medical management of patients when rapid transition to XR-naltrexone is needed.
MedicalResearch.com: Is there anything else you would like to add?
Response: We believe that these data offer a timely contribution to inform the development of clinical guidelines for detoxification from opioids and transition to XR-naltrexone treatment in an outpatient setting.
Potential limitations of the study include the heterogeneous prior experience in outpatient management of opioid detoxification among the study sites, the frequency and duration of study visits exceeded those common in outpatient practice and compensation for study participation may have encouraged study visits. Due to exclusion criteria of acute psychiatric needs, repeated failed opioid detoxification attempts or a positive urine drug test for methadone or buprenorphine at screening, the data may not be generalizable to such real-world patient populations. Finally, the low doses of oral naltrexone used are not FDA- approved and can only be obtained in a research setting or through a compounding pharmacy.
Disclosures: Maria Sullivan, M.D., Ph.D. is a full-time employee and shareholder of Alkermes, Inc. She also serves on the voluntary faculty of Columbia University as Associate Professor of Clinical Psychiatry.
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Adam Bisaga et al
Drug and Alcohol Dependence Volume 187, 1 June 2018, Pages 171-178
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