Journal Article Annotations
2017, 4th Quarter
Annotations by S. Alex Sidelnik, MD, and Diana Robinson, MD
Type of study: Randomized controlled trial
The finding: The study found that extended-release naltrexone (XR-NTX) was more difficult to initiate compared to buprenorphine-naloxone (BUP-NX), which negatively affected overall relapse rates. However, after successful initiation of XR-NTX, it was found to be equally effective as BUP-NX with regards to relapse rates and adverse events.
Strength and weaknesses: The study was a multicentre, open-label, randomized controlled trial of 24 weeks comparing XR-NTX with BUP-NX initiated during an acute inpatient detoxification admission. The primary outcome was time to relapse with secondary outcomes including proportion of patients successfully inducted, adverse events, and opioid craving. Among the intention-to-treat population, BUP-NX had a lower overall relapse rate compared to XR-NTX, which was related to initiation failures with XR-NTX. The study had a number of strengths including a relatively large sample size, long study duration, and good generalizability as the study was performed in typical community-based treatment settings. Despite a number of strengths, limitations included heterogeneity across treatment sites with regards to management of detoxification (opioid based versus non-opioid based), varied induction protocols among sites, which may have created variance in successful induction to XR-NTX, and applicability of the study in non-detoxification settings.
Relevance: The study demonstrated that although XR-NTX is more difficult to initiate, it was equally effective and safe compared to BUP-NX after successful initiation. In clinical practice, the study supports that among patients that are good candidates for XR-NTX, XR-NTX may be as effective as BUP-NX after successful initiation.
Type of study: Randomized controlled trial
The finding: This is a prospective, outpatient, randomized controlled study of treatment with extended-release naltrexone vs. buprenorphine-naloxone in for maintaining abstinence from heroin and other illicit substances in patients who recently underwent detoxification. 159 patients were randomized to treatment with extended-release naltrexone 380mg IM every 4 weeks (n=80pts; 50.3%) or buprenorphine-naloxone 4-24mg/day (n=79pts; 49.7%). The groups showed no significant differences in retention time in the study, total number of opioid-negative urine drug screens, days of use of heroin, and days of use of other illicit opioids. The authors concluded that extended-release naltrexone was as safe and effective as buprenorphine-naloxone at maintaining short term abstinence from heroin.
Strength and weaknesses: Strengths include study design of a prospective, randomized controlled trial of five urban sites from 2012-2015 with 159 randomized patients. To the authors’ knowledge, this is the first study comparing the effectiveness of extended-release naltrexone injections with that of daily oral buprenoprhine-naloxone for opioid medication treatment. Although cross-over data is pending, individuals who completed the 12 week RCT were invited to continue treatment or cross-over to the other treatment for 48 weeks.
Weaknesses include lack of blinding (authors stated they did not blind due to being unethical in the context of increased risk of opioid overdose after detoxification) and exclusion criteria that reduce the study population’s generalizability including excluding other substance use dependence or alcohol dependence, co-morbid psychiatric illness, or serious somatic illness. These are common concurrent diagnoses along with opioid dependence. Also, there was variability in opioid use in the 30 days prior to detoxification at the start of the study with some patients’ last use immediately prior to detoxification and others with sustained abstinence for varying periods of time due to incarceration or inpatient treatment . Additionally, details of the study design information were not included in the main body of the publication and were instead in the supplemental information.
Relevance: CL psychiatrists frequently evaluate patients with opioid dependence in the inpatient and outpatient settings that may benefit from induction or referrals for medication assisted treatment (MAT). It is important to educate ourselves on emerging options for MAT particularly when patients may be from low resource areas were addiction treatment services are difficult to access.