Short term health-related quality of life improvement during opioid agonist treatment
Introduction
As of 2012, there were approximately 2.5 million people in the United States who abused or were dependent on opioids; 2.1 million were dependent on prescription opioids (PO) such as oxycodone, but rates of heroin use may be increasing (Kuehn, 2013, Substance Abuse and Mental Health Services Administration, 2012). Opioid overdose is now the second leading cause of accidental death in the United States – surpassed only by motor vehicle accidents – and has been labeled a national epidemic (Centers for Disease Control and Prevention, 2011).
Opioid agonist treatment (OAT) with methadone (MET) or buprenorphine (BUP) has been shown to be effective in numerous randomized trials, meta-analyses, and large-scale longitudinal studies (Amato et al., 2005, Faggiano et al., 2003, Mattick et al., 2008). Methadone costs less and is more effective in retaining clients in treatment, while buprenorphine has a better safety profile and can be used in office-based practices in the US (Nosyk et al., 2013). Prolonged retention in treatment typically results in reductions in illicit drug use, behaviors that increase the risk of contracting HIV, and criminal activity (Amato et al., 2005). There is evidence that prescription opioid users are more likely to respond and be retained in OAT compared to heroin users (Moore et al., 2007, Nosyk et al., 2014, Soeffing et al., 2009). Discontinuing treatment typically results in relapse and elevated risk of mortality, with the risk of death after discontinuing treatment estimated to be 2.4 times greater than during treatment (Degenhardt et al., 2011).
Beyond clinical effectiveness, OAT has the potential to improve patients’ health-related quality of life (HRQoL) through reduction in drug use and withdrawal symptoms, decreased drug-seeking behavior and increased access to psychosocial and pharmacological treatment for co-morbid conditions, as recommended in best practices guidelines (Health Canada, 2005, National Consensus Development Panel on Effective Medical Treatment of Opiate Addiction, 1998). In recent years, evidence has accumulated for the improvement of HRQoL during long-term opioid agonist treatment for heroin-dependent individuals (Giacomuzzi et al., 2003, Karow et al., 2010, Korthuis et al., 2011, Nosyk et al., 2011, Ponizovsky and Grinshpoon, 2007, Winklbaur et al., 2008).
In most instances, however, HRQoL gains have been modest in magnitude. For instance, a prior study of chronic heroin-dependent individuals revealed modest immediate HRQoL improvement, which declined slightly over time during OAT. Critically, these gains were only observed in a subset of 61% of the study cohort, with 20% demonstrating no HRQoL response despite sustained engagement in treatment (Nosyk et al., 2011). Furthermore, an increasing proportion of OAT clients in the US are presenting with PO dependence (Nosyk et al., 2014), often receiving buprenorphine treatment in office-based settings (Kleber, 2008) in either time-limited (i.e., detoxification) or time-unlimited treatment regimens. There is a paucity of research on the potential differential effects on HRQoL of disparate treatment modalities, or whether greater gains are achievable in PO dependence compared to heroin dependence, considering the latter may be associated with more concurrent medical problems such as Hepatitis C (Suryaprasad et al., 2014).
These distinctions may be consequential in the context of health economic evaluations, which rely on health state-specific HRQoL measures to evaluate quality-adjusted life year benefits in comparative analyses of competing treatment regimens. Substance use disorder treatment is typically accessed several times over an individual's drug use career given the chronic, recurrent nature of opioid dependence (McLellan et al., 2000). Information on the impact of repeated treatment attempts, and the durability of the impact of treatment on HRQoL, are critical to the accurate estimation of relative value for money of alternative substance use disorder treatment modalities, including medications. Uncertainty surrounding HRQoL valuations had an effect on the findings in at least one prior cost-effectiveness analysis for the treatment of opioid dependence (Schackman et al., 2012). Our objective was therefore to characterize short-term changes in HRQoL following enrollment into OAT across different modalities (detoxification, or tapered-dose treatment, maintenance, or time-unlimited treatment), medications (buprenorphine, methadone) and patient subgroups (heroin, PO dependence).
Section snippets
Study populations
This study was a secondary analysis of two multi-site, US-based randomized controlled trials executed by the NIDA-supported Clinical Trials Network. Characteristics of the trials and participants are described in Table 1, and results of the trials are summarized elsewhere (Potter et al., 2013, Weiss et al., 2011). The Starting Treatment with Agonist Replacement Therapies (START) trial was a 24-week multi-site phase-IV trial designed to compare OAT with methadone and buprenorphine/naloxone
Results
Patient subgroup selection from the START and POATS trials is described in Fig. 1. Of note, 88 individuals from the START trial were excluded due to missing baseline data on self-reported opioid use. Among selected participants providing final follow-up assessments, 158 were PO-dependent while 545 were heroin dependent individuals. A total of 653 POATS participants completed assessments during short-term taper, with 313 completing assessments during extended stabilization and taper. After
Discussion
We found that OAT, whether delivered in time-unlimited (maintenance) or detoxification, using buprenorphine/naloxone or methadone, is associated with modest improvements in HRQoL soon after treatment initiation that is near conventional minimally important difference level for the SF-6D (0.041; Walters and Brazier, 2005), with diminishing, and possibly deteriorating benefits thereafter. This observed pattern of immediate increase and diminishing or leveling off is consistent with at least two
Role of funding source
This research was supported in part by the National Institute on Drug Abuse (NIDA) (R01-DA033424 and R01-DA031727). Dr. Weiss was otherwise supported by grants U10-DA15831 and K24-DA022288 from NIDA. The funders had no role in the design or conduct of the study, interpretation of the data or decision to submit the paper for publication.
Author contributions
BN, JWB, EW, BA, AAE and BRS contributed to the design of the study. BN led the analysis and preparation of the manuscript. JWB contributed to analysis and interpretation of results. RDW, JP, AA, YI and WL led procurement of the databases. All authors provided critical revisions to the article and approved the final draft.
Conflict of interest
None.
Acknowledgements
We gratefully acknowledge the editorial support of Michelle Olding and assistance of representatives of the CTN study teams, including Maureen Hillhouse and Albert Hasson, for their helpful insight into the studies and databases.
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2020, Drug and Alcohol DependenceCitation Excerpt :A second difference pertains to data sources. Krebs et al. (2016) analyzed pooled data from multiple cohort studies of persons with OUD who had ever accessed opioid agonist therapy, and Nosyk et al. (2015) analyzed data from two clinical trials that enrolled heroin or prescription opioid dependent persons; our analysis is based on a single clinical trial of BUP-NX versus XR-NTX among persons seeking treatment in an inpatient or residential setting, continuing treatment as outpatients. Finally, we were able to take advantage of more frequently collected HRQoL assessments over time than Nosyk et al. (2015); and more frequently collected HRQoL assessments from a greater number of participants than Nosyk et al. (2011) and Krebs et al. (2016).