Elsevier

Drug and Alcohol Dependence

Volume 205, 1 December 2019, 107649
Drug and Alcohol Dependence

Full length article
Trajectory classes of opioid use among individuals in a randomized controlled trial comparing extended-release naltrexone and buprenorphine-naloxone

https://doi.org/10.1016/j.drugalcdep.2019.107649Get rights and content

Highlights

  • We examined opioid use trajectories for patients treated for OUD.

  • BUP-NX had four distinct opioid use trajectory classes.

  • XR-NTX had three distinct opioid use trajectory classes.

  • In BUP-NX and XR-NTX, the near abstinent opioid class had greater treatment visits.

  • Within XR-NTX, Hispanic ethnicity was a predictor of opioid use trajectory.

Abstract

Objectives

To advance our understanding of medication treatments for opioid use disorders (OUDs), identification of distinct subgroups and factors associated with differential treatment response is critical. We examined trajectories of opioid use for patients with OUD who were randomized to (but not in all cases inducted onto) buprenorphine-naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and identified characteristics associated with each trajectory.

Methods

Growth mixture models (GMMs) were run to identify distinct trajectories of days of opioid use among a subsample of 535 individuals with OUD who participated in a 24-week randomized controlled trial (RCT; 2014–2016) of BUP-NX (n = 281) or XR-NTX (n = 254).

Results

Four distinct opioid use trajectory classes were identified for BUP-NX (near abstinent/no use (59%); low use (13.2%); low use, increasing over time (15%); and moderate use, increasing over time (12.8%)). Three distinct opioid use trajectory classes were found for XR-NTX (near abstinent/no use (59.1%); low use (14.6%); and moderate use, increasing over time (26.4%)). Across both BUP-NX and XR-NTX, the near abstinent/no use class had the highest number of medical management visits. Within BUP-NX, the low use class had a greater proportion of individuals with a previous successful treatment history compared with other classes. Within XR-NTX, the moderate use, increasing over time class had the highest proportion of Hispanic participants compared with other classes.

Conclusions

Findings highlight the significant heterogeneity of opioid use during a RCT of BUP-NX and XR-NTX and factors associated with opioid use patterns including medical management visits and history of treatment success.

Introduction

More than 2.1 million people in the U.S. have an opioid use disorder (OUD), a chronic condition with 65%–84% of individuals relapsing within a month after completing inpatient or outpatient detoxification (Bailey et al., 2013; Day and Strang, 2011). Opioid overdose deaths have steadily increased over the last 15 years with 47,600 reported in 2017 (Center for Disease Control and Prevention, 2019). Synthetic opioids (other than methadone) such as the highly potent fentanyl, fentanyl analogs, and tramadol are responsible for more than half (29,000) of opioid-related overdose deaths (National Institute on Drug Abuse (NIDA), 2018); between 2002 and 2017 there was a 22-fold increase in the total number of overdose deaths attributable to synthetic opioids. Thus, there is a dire need to identify more effective and targeted methods of treating OUD.

Three pharmacologically distinct FDA-approved medications for OUD (MOUD) have been found to be effective, the full opioid agonist methadone, the partial agonist buprenorphine-naloxone [BUP-NX], and the antagonist naltrexone formulated as an extended-release injection [XR-NTX]. These are considered front-line treatments (Volkow, 2018) and traditionally combined with psychosocial interventions to provide comprehensive care. Methadone in the U.S. is only available in regulated specialty settings (i.e., Opioid Treatment Programs), while BUP-NX and XR-NTX can be prescribed across a range of healthcare settings, and have the potential to increase the accessibility of MOUD. BUP-NX and XR-NTX each have unique induction requirements portending distinct challenges in initiation and maintenance of treatment among patients. This is particularly true of XR-NTX which requires patients to be fully detoxified from opioids (e.g., no opioids for approximately 7–10 days; Jarvis et al., 2018); however, once induction hurdles are overcome, XR-NTX appear to be as effective as BUP-NX (Lee et al., 2018; Tanum et al., 2017). For example, a multi-site randomized controlled trial (RCT) comparing daily oral BUP-NX with flexible dosing (from 4 to 24 mg/day) to monthly intramuscular XR-NTX (380 mg) revealed no differences between the medications in reducing opioid and other illicit drug use in the short-term (i.e., 12 weeks; Tanum et al., 2017). A multi-site RCT in the United States, compared BUP-NX (administered sublingually via film) to XR-NTX (administered monthly via intramuscular injection), in a sample of individuals with OUD, over 24 weeks (Lee et al., 2018). Although significantly fewer participants successfully initiated XR-NTX, among those who were fully inducted on either XR-NTX or BUP-NX (per protocol treatment groups), there were no significant differences between the two treatments in weeks to relapse, opioid-negative urines, and self-reported opioid abstinent days. Thus, although XR-NTX may present unique induction challenges, studies support its efficacy as an additional treatment for OUD.

While the aforementioned trials provided important information on mean-level differences in rates of opioid use and relapse, there is scarce information on the variability in how individuals’ opioid use changes over time while receiving MOUD. Identifying differential use patterns and treatment response and the characteristics that predict them is critical in understanding how MOUD work among subgroups of individuals, and can inform the timing and targeting of intervention efforts (Grella and Lovinger, 2011; Hser et al., 2017; Teesson et al., 2017). The limited research to date has demonstrated heterogeneity in opioid use trajectories for people on MOUD. In a sample of 795 people who use opioids and participated in a RCT of methadone or BUP-NX, Hser et al. (2017) identified 4 opioid use trajectories over time (up to 55 months posttreatment): low use, high use, decreasing use, and increasing use. More than 40% of the participants were in the low use group (demonstrating consistently low opioid use over time) after MOUD treatment. Eastwood and colleagues (2018) examined opioid use trajectories in a sample of 7719 individuals continuously enrolled in community based MOUD (methadone or buprenorphine) for at least five years and followed posttreatment for another two years. They found five heroin use trajectory classes: gradual decreasing, decreasing then increasing, continued low-level, rapid decreasing, and continued high-level (Eastwood et al., 2018). Variables that predicted non-response to treatment included current injection drug use, previous treatment, and higher social deprivation. These studies demonstrated variability in MOUD treatment response and highlight the benefit of adherence to treatment. Overall, studies show the strongest predictor of abstinence over follow-up was being on MOUD (Weiss et al., 2015). Findings underscore the need to identify treatment response early in the course of treatment to modify and optimize treatment interventions. Notably, no studies have examined patterns of treatment response during the first 24 weeks of treatment and in particular among patients randomized to XR-NTX.

The aim of this secondary analysis was to examine trajectories of opioid use for patients with OUD who were randomized to receive 24 weeks of treatment with either BUP-NX or XR-NTX, and to identify characteristics associated with each trajectory class. In particular, we were interested in exploring opioid use trajectories among individuals randomized to XR-NTX since this analysis had not previously been conducted.

Section snippets

Study design and participants

This is a secondary data analysis of a multi-site 24-week open-label randomized effectiveness and safety trial comparing XR-NTX and BUP-NX for OUD. The detailed protocol (Lee et al., 2016; Nunes et al., 2016) and primary outcome analysis (Lee et al., 2018) have been previously published.

Descriptive statistics

Table 1 presents demographic characteristics for the intent-to-treat (ITT; N = 570) sample and the retained subsample (RS) of 535 participants who had at least one time point for the outcome observation. ITT participants were predominantly white men, with a mean age of 33.9 (SD = 9.6), single, unemployed, and Medicaid-insured. Approximately 17% self-identified as Hispanic. Sixty-eight percent used drugs intravenously, and overall had been using opioids, on average, for 12.5 years (SD = 9.0).

Discussion

To advance our understanding of MOUD treatment response, the identification of distinct subgroups and factors associated with differential treatment response is critical to inform intervention efforts in terms of optimal targets and intervention leverage points. This secondary analysis identified four distinct opioid use trajectories for BUP-NX and three distinct opioid use trajectories for XR-NTX. Overall, the trajectory classes for XR-NTX and BUP-NX were quite similar (i.e., both had “near

Role of funding source

This research was supported by grants from the NIDA National Drug Abuse Treatment Clinical Trials Network (U10DA013046, UG1/ U10DA013035, UG1/U10DA013034, U10DA013045, UG1/U10DA013720, UG1/U10DA013732, UG1/U10DA013714, UG1/U10DA015831, U10DA015833, HHSN271201200017C, and HHSN271201500065C) and K24DA022412 (EVN Jr). The NIDA did not have a role in the study design, collection, analysis, and interpretation of data; nor in the writing of the report, or the decision to submit the article for

Contributors

LMR conceptualized and designed the research question. JS and MP conducted the statistical analyses. All authors drafted the initial manuscript, interpreted results, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted.

Declaration of Competing Interest

The authors declare no conflicts of interest.

Acknowledgments

We thank the reviewers on the NIDA National Drug Abuse Treatment Clinical Trials Network Publication Committee for their review and feedback on this manuscript.

References (33)

Cited by (15)

  • Predictors of therapeutic alliance, treatment feedback, and clinical outcomes among African American women in treatment for co-occurring PTSD and SUD

    2022, Journal of Substance Abuse Treatment
    Citation Excerpt :

    Number of prior substance use treatments also positively predicted early alliance. Dennis et al. (2005) demonstrated that multiple treatment attempts are common for individuals with SUDs who later achieve long-term abstinence and recovery, and successes in prior treatment have been associated with positive SUD outcomes, including reduced substance use (Ruglass et al., 2019). These findings reinforce the relevance of SUD chronicity and demonstrate a cumulative latent benefit of having multiple prior treatment experiences, possibly preparing individuals for what to expect in therapy or increasing readiness to change.

  • Racial/ethnic disparities in the use of medications for opioid use disorder (MOUD) and their effects on residential drug treatment outcomes in the US

    2021, Drug and Alcohol Dependence
    Citation Excerpt :

    Improved access to MOUD in ST residential treatment settings may be a particularly critical component for successful OUD treatment for disadvantaged minority patients. The enhanced outcomes associated with MOUD for Black and Hispanic patients in ST residential treatment is particularly noteworthy given that prior research has shown that minority patients often have worse residential treatment outcomes in general (Bluthenthal et al., 2007; Mennis and Stahler, 2016; Mutter et al., 2015; Saloner and Lê Cook, 2013; Stahler et al., 2016) as well as worse MOUD retention and outcomes in outpatient settings (Gaither et al., 2018; Ruglass et al., 2019; Samples et al., 2018; Zhu et al., 2018). Residential treatment is often a preferred modality for those who need a more structured and intensive treatment setting where there is greater compliance with treatment medications and may be more therapeutically appropriate for those with greater addiction severity, co-occurring mental health disorders, and multiple unsuccessful outpatient treatment episodes (Blum et al., 2014; Eastwood et al., 2017; de Andrade et al., 2019).

  • Endogenous opiates and behavior: 2019

    2021, Peptides
    Citation Excerpt :

    The OPRD1 genotype at rs678849 was associated with buprenorphine efficacy in African-Americans with opioid use disorder [173]. Opioid use was similar among individuals receiving extended-release naltrexone or buprenorphine-naloxone [750]. Buprenorphine/naloxone take-home doses enabled opiate agonist treatment [220].

View all citing articles on Scopus

This research was supported by grants from the NIDA National Drug Abuse Treatment Clinical Trials Network (U10DA013046, UG1/ U10DA013035, UG1/U10DA013034, U10DA013045, UG1/U10DA013720, UG1/U10DA013732, UG1/U10DA013714, UG1/U10DA015831, U10DA015833, HHSN271201200017C, and HHSN271201500065C) and K24DA022412 (EVN Jr).

View full text