Relative effectiveness of medications for opioid-related disorders: A systematic review and network meta-analysis of randomized controlled trials

Abstract

Introduction Several pharmacotherapeutic interventions are available for maintenance treatment for opioid-related disorders. However, previous meta-analyses have been limited to pairwise comparisons of these interventions, and their efficacy relative to all others remains unclear. Our objective was to unify findings from different healthcare practices and generate evidence to strengthen clinical treatment protocols for the most widely prescribed medications for opioid-use disorders. Methods We searched Medline, EMBASE, PsycINFO, CENTRAL, and ClinicalTrials.gov for all relevant randomized controlled trials (RCT) from database inception to February 12, 2022. Primary outcome was treatment retention, and secondary outcome was opioid use measured by urinalysis. We calculated risk ratios (RR) and 95% credible interval (CrI) using Bayesian network meta-analysis (NMA) for available evidence. We assessed the credibility of the NMA using the Confidence in Network Meta-Analysis tool. Results Seventy-nine RCTs met the inclusion criteria. Due to heterogeneity in measuring opioid use and reporting format between studies, we conducted NMA only for treatment retention. Methadone was the highest ranked intervention (Surface Under the Cumulative Ranking [SUCRA] = 0.901) in the network with control being the lowest (SUCRA = 0.000). Methadone was superior to buprenorphine for treatment retention (RR = 1.22; 95% CrI = 1.06–1.40) and buprenorphine superior to naltrexone (RR = 1.39; 95% CrI = 1.10–1.80). However, due to a limited number of high-quality trials, confidence in the network estimates of other treatment pairs involving naltrexone and slow-release oral morphine (SROM) remains low. Conclusion All treatments had higher retention than the non-pharmacotherapeutic control group. However, additional high-quality RCTs are needed to estimate more accurately the extent of efficacy of naltrexone and SROM relative to other medications. For pharmacotherapies with established efficacy profiles, assessment of their long-term comparative effectiveness may be warranted. Trial Registration This systematic review has been registered with PROSPERO (https://www.crd.york.ac.uk/prospero) (identifier CRD42021256212).

History of the discovery, development, and FDA-approval of buprenorphine medications for the treatment of opioid use disorder

“…MOUD combined with psychosocial interventions is the most effective treatment option for patients suffering from OUD ( ASAM, 2020 ; Connock et al., 2007 ; Dugosh et al., 2016 ). MOUD has been shown to be associated with positive outcomes for reducing drug use, criminal activity ( Gisev et al., 2019 ; Gossop et al., 2000 ; Oliver et al., 2010 ; Røislien et al., 2014 ), risk behaviors and HIV-transmission ( Marsch 1998 ), overdoses, and overall mortality ( Gisev et al., 2015 ; Sordo et al., 2017 ) as well as improving rates of retention in treatment ( Lim et al., 2022 ).…”

The effects of naltrexone on retention in treatment and being opioid-free in opioid-dependent people: A systematic review and meta-analysis

“…Additionally, a previous systematic review of 14 studies revealed non-statistically significant results for successful completion of treatment (OR = 0.78; 95% CI, 0.34–1.75) and use of opioids under treatment (OR = 0.85; 95% CI, 0.45–1.62) ( 35 ). A network meta-analysis conducted by Lim and colleagues which aimed to evaluate the effectiveness of different medication types for opioid-related disorders showed that the likelihood of treatment retention was statistically significantly higher for naltrexone than for controls [relative risk (RR) = 1.54; 95% CI, 1.26–1.90], and showed the average percent of treatment retention of 41.0% for naltrexone among all included studies ( 36 ). Furthermore, the RRs for the effectiveness of naltrexone compared with buprenorphine, methadone, and slow-release oral morphine were 0.72 (95% CI, 0.55–0.91), 0.59 (95% CI, 0.45–0.77), and 0.62 (95% CI, 0.38–0.99), respectively ( 36 ).…”

“…A network meta-analysis conducted by Lim and colleagues which aimed to evaluate the effectiveness of different medication types for opioid-related disorders showed that the likelihood of treatment retention was statistically significantly higher for naltrexone than for controls [relative risk (RR) = 1.54; 95% CI, 1.26–1.90], and showed the average percent of treatment retention of 41.0% for naltrexone among all included studies ( 36 ). Furthermore, the RRs for the effectiveness of naltrexone compared with buprenorphine, methadone, and slow-release oral morphine were 0.72 (95% CI, 0.55–0.91), 0.59 (95% CI, 0.45–0.77), and 0.62 (95% CI, 0.38–0.99), respectively ( 36 ). Our study showed that naltrexone increased retention to treatment by 63.8% compared to the control group, which was not significant (95% CI, 0.78–3.44).…”

“…In this regard, the article by Timko et al showed a wide range of rates of retention in treatment for opioid dependence from 3–88% at 3-months to 37–91% at 12-months of follow-up ( 37 ). Overall, naltrexone was the fourth most effective medication among medications for opioid-related disorders than controls in terms of treatment retention after methadone (RR = 2.62), and slow-release oral morphine (RR = 2.52), and buprenorphine (RR = 2.15) ( 36 ). The better efficacy of methadone for treatment retention was also shown in another study by ( 37 ).…”

Associations of methadone and buprenorphine‐naloxone doses with unregulated opioid use, treatment retention, and adverse events in prescription‐type opioid use disorders: Exploratory analyses of the OPTIMA study

“…Overall, there is limited evidence regarding the effectiveness of various doses of BUP‐NX and methadone in the treatment of OUD for people who mainly use prescription‐type opioids (from prescription or unregulated sources), and not heroin. Most efficacy studies were conducted when heroin was the main opioid used, with only a few studies having been conducted in people with OUD since the use of extremely potent opioids such as fentanyl has become common 8,22 . Also, these studies have been conducted in clinical settings with stricter OAT dosing schedules so that results cannot be confidently used to guide practice in real‐world clinical settings in which flexible OAT doses are implemented 8,22 .…”