Polysubstance Use in Adults With Opioid Use Disorder Receiving Buprenorphine Maintenance.

INTRODUCTION: Studying polysubstance use is a public health recommendation. In the United Arab Emirates, more than 80% of adults with opioid use disorder (OUD) use 2 or more nonopioid substances. This secondary analysis contrasts the characteristics of polysubstance users (OUD + ≥1 nonopioid) with OUD, explores the correlates and predictors of nonfatal overdose, and examines the impact of polysubstance use on OUD treatment outcomes using buprenorphine (BUP). METHODS: This analysis uses data from a 16-week outpatient randomized controlled trial of 141 adults with OUD allocated to BUP + incentivized adherence and abstinence monitoring (n = 70) and BUP in usual care (control, n = 71). Outcomes were nonfatal overdose events over the preceding 12 months, positive drug screens, and treatment retention. Participant characteristics were contrasted, and bivariate statistical tests were conducted for simple associations followed by logistic regression. RESULTS: Polysubstance use was reported by 117 participants (82.9%), the majority of whom used pregabalin 72.1% (n = 75). Compared with OUD, polysubstance users observed higher arrests (median, 1.0 [interquartile range, 0.0-3.0] vs 0.5 [interquartile range, 0.0-2.0]; P = 0.04]) and nonfatal overdose events (n = 33 [31.8%] vs 2 [10.8%], P = 0.003). Carisoprodol and injecting drug use independently predicted nonfatal overdose (adjusted odds ratio, 4.519 [95% confidence interval, 1.81-11.22] and 2.74 [95% confidence interval, 1.15-6.51], respectively). No significant difference was observed in opioid use and retention in treatment outcomes between groups. CONCLUSION: Carisoprodol and injecting drug use increase the likelihood of nonfatal overdose in adults with OUD. Polysubstance use does not impact response to BUP treatment compared with OUD.

Lower buprenorphine elimination rate constant is associated with lower opioid use.

BACKGROUND: Opioid craving is suggested to correlate with the rate of reduction in buprenorphine (BUP) plasma levels. No studies explored Buprenorphine elimination rate constant (BUP EL.R) as a predictor of opioid use or retention in BUP treatment. METHODS: Analysis was performed using data from a randomized controlled trial of 141 adults with opioid use disorder (OUD) randomized to Incentivized Adherence and Abstinence monitoring (I-AAM; experimental (n = 70) and treatment-as-usual; control (n = 71). In the I-AAM, structured access to unsupervised BUP doses was provided up to 28 days contingent of adherence measured by Therapeutic Drug Monitoring and abstinence by Urinary Drug Screens (UDS). In contrast, the treatment-as-usual (control) provided unstructured access to unsupervised doses was provided for up to 14 days considering UDS results. The primary outcome was percentage negative UDS. The secondary outcome, retention in treatment, was continuous enrollment in the study and analysis was via intention-to-treat. Significant bivariate correlations with the outcomes were adjusted for group allocation. RESULTS: A significant negative correlation between BUP EL.R and percentage negative opioid screens (Pearson correlation coefficient - 0.57, p < 0.01) was found. After adjusting for trial group, BUP EL.R was shown to be an independent predictor of percentage negative opioid screens (Standardized Beta Coefficient - 0.57, 95% CI - 221.57 to - 97.44, R2 0.322). CONCLUSION: BUP EL.R predicted 32.2% of the variation in percentage negative opioid UDS and may serve as a potential promising tool in precision medicine of BUP treatment. Higher buprenorphine elimination is associated with higher positive opioid urine screens during treatment. TRIAL REGISTRATION: ISRCTN41645723 retrospectively registered on 15/11/2015.

The impact of family engagement in opioid assisted treatment: Results from a randomised controlled trial.

BACKGROUND: Family interventions in substance use disorders (SUD) treatment is limited despite the evidence for benefits. Providing family interventions is hampered by patient resistance, social stigma, logistics and factors related to the capacity of the treatment programmes. AIMS: The purpose of the study was to examine the association between family engagement in treatment, and opioid use defined by percentage negative opioid screen and rate retention in treatment defined by completion of study period. METHODS: Data from a 16-week outpatient randomised controlled trial (RCT) of 141 adults with opioid use disorder (OUD) receiving Opioid Assisted Treatment (OAT) using buprenorphine/naloxone film (BUP/NX-F) was, used to examine the association between family engagement in and opioid use and rate of retention in treatment. Multiple logistic regression was, applied to examine the independent prediction of family engagement on opioid use and rate retention in treatment. RESULTS: Family engagement was significantly associated with retention in treatment (Spearman's rho 0.25, p < 0.01) and was subsequently found to increase the likelihood of retention in treatment by approximately 3-fold (adjusted odds ratio (OR) 2.95, 95% CI 1.31-6.65). CONCLUSION: Family engagement in treatment is an independent predictor of retention in treatment but not opioid use in adults receiving OAT. It is, recommended that SUD treatment programmes integrate family related interventions in mainstream treatment. Delivering a personalised multicomponent family programme using digitised virtual communications that has been increasingly utilised during the Covid-19 pandemic is highly suggested.

Exploratory Economic Evaluation of Buprenorphine Treatment in Opioid Use Disorder.

BACKGROUND: Burden of opioid use disorder (OUD) is expressed in economic values or health metrics like Disability Adjusted Life Years (DALYs). Disability Weight (DW), a component of DALYs is estimated using economic methods or psychometric tools. Estimating DW at patient level using psychometric tools is an alternative to non-population specific DW overestimated by economic methods. Providing Medication Assisted Treatment (MAT) using buprenorphine/naloxone film (BUP/NX-F) for OUD is limited by financial constraints. AIM: To estimate the burden of OUD at patient level and explore the cost-benefit of two buprenorphine treatment interventions. METHODS: The present study was conducted alongside a randomized controlled trial of 141 adults with OUD stabilized on BUP/NX-F and randomized to BUP/NX-F with Incentivized Abstinence and Adherence Monitoring (experimental, n=70) and BUP/NX-F in usual care (control, n=71). The cost of illness was estimated applying a societal perspective. The Impairment Weight (IW) was estimated over a '0' to '1' scale, where '0' represents no impairment and '1' full impairment using the Work and Social Adjustment Scale (WSAS). RESULTS: Median (interquartile range) annual cost of OUD per participant was AED 498,171.1 (413,499.0 -635,725.3) and AED 538,694.4 (4,211,398.0 - 659,949.0) in the experimental and control groups, respectively (p=0.33). Illicit drug purchase represented 60 % of the annual cost of illness. At baseline, the mean Impairment Weight (IW) was 0.55 (SD 0.26) and 0.62 (SD 0.24) in the experimental and control groups, respectively. At end of the study, the IW was 0.26 (SD 0.28) representing 51% reduction in the experimental group compared to 0.42 (SD 0.33) in the control group representing a 27% reduction. Excluding imprisonment, the cost-benefit of treatment was not realized. In contrast, accounting for imprisonment, cost benefit expressed as a return-on-investment was established at 1.55 and 1.29 in the experimental and control groups, respectively. IMPLICATIONS FOR MENTAL HEALTH POLICY: Cost benefit analysis can serve as a simple and practical tool to evaluate the cost benefit of treatment interventions. Demonstrating the cost benefit of buprenorphine treatment has the potential to facilitate public funding and accessibility to opioid assisted treatment.

Effectiveness of incentivised adherence and abstinence monitoring in buprenorphine maintenance: a pragmatic, randomised controlled trial.

BACKGROUND AND AIM: Buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD) begins with supervised daily dosing. We estimated the clinical effectiveness of a novel incentivised medication adherence and abstinence monitoring protocol in BUP maintenance to enable contingent access to increasing take-home medication supplies. DESIGN: Two-arm, single-centre, pragmatic, randomised controlled trial of outpatient BUP maintenance, with during-treatment follow-ups at 4 weeks, 8 weeks, 12 weeks and 16 weeks. SETTING: Inpatient and outpatient addictions treatment centre in the United Arab Emirates. PARTICIPANTS: Adults with OUD, voluntarily seeking treatment. INTERVENTIONS: The experimental condition was 16 weeks BUP maintenance with incentivised adherence and abstinence monitoring (I-AAM) giving contingent access to 7-day, then 14-day, then 21-day and 28-day medication supply. The control, treatment-as-usual (TAU) was 16 weeks BUP maintenance, with contingent access to 7-day then 14-day supply. MEASUREMENTS: The primary outcome was number of negative urine drug screens (UDS) for opioids, with non-attendance or otherwise missed UDS, imputed as positive for opioids. The secondary outcome was retention in treatment (continuous enrolment to the 16-week endpoint). FINDINGS: Of 182 patients screened, 171 were enrolled and 141 were randomly assigned to I-AAM (70 [49.6%]) and to TAU (71 [50.4%]. Follow-up rates at 4 weeks, 8 weeks, 12 weeks and 16 weeks were 91.4%, 85.7%, 71.0%, 60.0% respectively in I-AAM and 84.5%, 83.1%, 69.0%, 56.3% in TAU. By intention-to-treat, the absolute difference in percentage negative UDS for opioids was 76.7% (SD = 25.0%) in I-AAM versus 63.5% (SD = 34.7%) in TAU (mean difference = 13.3%; 95% CI = 3.2%-23.3%; Cohen's d = 0.44; 95% CI = 0.10-0.87). In I-AAM, 40 participants (57.1%) were retained versus 33 (46.4%) in TAU (odds ratio = 1.54; 95% CI = 0.79-2.98). CONCLUSIONS: Buprenorphine maintenance with incentivised therapeutic drug monitoring to enable contingent access to increasing take-home medication supplies increased abstinence from opioids compared with buprenorphine maintenance treatment-as-usual, but it did not appear to increase treatment retention.

Therapeutic Drug Monitoring in Buprenorphine/Naloxone Treatment for Opioid Use Disorder: Clinical Feasibility and Optimizing Assay Precision.

INTRODUCTION: Compliance with sublingual buprenorphine/naloxone (SL-BUP/NX) is associated with higher abstinence from illicit opioid use. Therapeutic drug monitoring (TDM) has been recommended for adherence monitoring of buprenorphine (BUP) maintenance treatment for opioid use disorder (OUD), but to date there have been no reported clinical applications. In this TDM feasibility study, we investigated BUP assay precision in 15 adults with OUD who had been stabilized on buprenorphine/naloxone. METHODS: Using solid phase extraction, BUP recovery was contrasted at 100 mMol and 1 Molar of acetic acid wash solution. Precision was determined by applying the condition generating highest recovery using 0.2 ng/mL and 10 ng/mL standards. Four blood samples were drawn to examine the BUP peak and trough plasma concentrations, and BUP elimination rate was estimated. BUP recovery was examined again in a random sample and contrasted with the concentration predicted applying first-order kinetics. RESULTS: Higher BUP recovery was achieved with 1 Molar wash (94.3%; p=0.05). Precision ranged from 15-20%. The estimated limit of detection (LoD) and limit of quantitation (LoQ) were 0.02 and 0.069 ng/mL, respectively. BUP peak and trough concentrations were successfully examined, and BUP trough concentrations were replicated confirming steady state. BUP concentrations were predicted at a variance of -7.20% to 1.54 %. CONCLUSIONS: TDM for BUP maintenance treatment of OUD is feasible, and simple adjustment of the assay conditions enhances BUP recovery.