Interim opioid agonist treatment for opioid addiction: a systematic review.

BACKGROUND: Opioid use disorder is a public health problem and treatment variability, coverage and accessibility poses some challenges. The study's objective is to review the impact of interim opioid agonist treatment (OAT), a short-term approach for patients awaiting standard OAT, in terms of treatment retention, access to standard OAT, quality of life and satisfaction with treatment. METHOD: We conducted a systematic review searching MEDLINE, EMBASE, PsycINFO, and CENTRAL up to May 2020. Due to variability between studies and outcome measurements, we did not pool effect estimates and reported a narrative synthesis of findings rating their certainty according to GRADE. RESULTS: We identified 266 unique records and included five randomized trials with some limitations in risk of bias and one observational study limited by selection bias. The studies assessed similar approaches to interim OAT but were compared to three different control conditions. Four studies reported on treatment retention at 4 months or less with no significant differences between interim OAT and waiting list or standard OAT. Two studies reported treatment retention at 12 months with no differences between interim OAT and standard OAT. Two trials assessed access to standard OAT and showed significant differences between interim OAT and waiting list for standard OAT. We rated the quality of evidence for these outcomes as moderate due to the impact of risk of bias. Data on quality of life or satisfaction with treatment was suboptimal. CONCLUSIONS: Interim OAT is likely more effective than a waiting list for standard OAT in access to treatment, and it is probably as effective as standard OAT regarding treatment retention. PROSPERO registration CRD42018116269.

Posttraumatic stress disorder in individuals seeking treatment for opioid use disorder in Vermont.

Posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) may be associated with poor outcomes in rural areas where access to mental health services and opioid agonist treatment (OAT) is limited. This study examined the characteristics associated with a history of PTSD among a sample of individuals seeking buprenorphine treatment for OUD in Vermont, the second-most rural state in the US. Participants were 89 adults with OUD who participated in one of two ongoing randomized clinical trials examining the efficacy of an interim buprenorphine dosing protocol for reducing illicit opioid use during waitlist delays to OAT. Thirty-one percent of participants reported a history of PTSD. Those who did (PTSD+; n = 28) and did not (PTSD-; n = 61) report a history of PTSD were similar on sociodemographic and drug use characteristics. However, the PTSD+ group was less likely to have received prior OUD treatment compared to the PTSD- group (p = .02) despite being more likely to have a primary care physician (p = .009) and medical insurance (p = .002). PTSD+ individuals also reported greater mental health service utilization, more severe psychiatric, medical and drug use consequences, and greater pain severity and interference vs. PTSD- individuals (ps < 0.05). These findings indicate that a history of PTSD is prevalent and associated with worse outcomes among individuals seeking treatment for OUD in Vermont. Dissemination of screening measures and targeted interventions may help address the psychiatric and medical needs of rural individuals with OUD and a history of PTSD.

Impact of Current Pain Status on Low-Barrier Buprenorphine Treatment Response Among Patients with Opioid Use Disorder.

OBJECTIVE: Chronic non-cancer pain (CNCP) is prevalent among individuals with opioid use disorder (OUD). However, the impact of CNCP on buprenorphine treatment outcomes is largely unknown. In this secondary analysis, we examined treatment outcomes among individuals with and without CNCP who received a low-barrier buprenorphine maintenance regimen during waitlist delays to more comprehensive opioid treatment. METHODS: Participants were 28 adults with OUD who received 12 weeks of buprenorphine treatment involving bimonthly clinic visits, computerized medication dispensing, and phone-based monitoring. At intake and monthly follow-up assessments, participants completed the Brief Pain Inventory, Beck Anxiety Inventory, Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI), Addiction Severity Index, and staff-observed urinalysis. RESULTS: Participants with CNCP (n = 10) achieved comparable rates of illicit opioid abstinence as those without CNCP (n = 18) at weeks 4 (90% vs 94%), 8 (80% vs 83%), and 12 (70% vs 67%) (P = 0.99). Study retention was also similar, with 90% and 83% of participants with and without CNCP completing the 12-week study, respectively (P = 0.99). Furthermore, individuals with CNCP demonstrated significant improvements on the BDI-II and Global Severity Index subscale of the BSI (P < 0.05). However, those with CNCP reported more severe medical problems and smaller reductions in legal problems relative to those without CNCP (P = 0.03). CONCLUSIONS: Despite research suggesting that chronic pain may influence OUD treatment outcomes, participants with and without CNCP achieved similar rates of treatment retention and significant reductions in illicit opioid use and psychiatric symptomatology during low-barrier buprenorphine treatment.

Interim buprenorphine treatment in opiate dependence: A pilot effectiveness study.

BACKGROUND: Interim methadone treatment (i.e., temporary medication-only treatment) has been tested in a few U.S. studies as a method for facilitated referral to and initiation of opioid maintenance treatment in heroin dependence. However, despite the favorable safety profile of buprenorphine compared with methadone, interim treatment with buprenorphine rarely has been tested and reported in the scientific literature. The present pilot effectiveness study aims to assess the feasibility of an interim buprenorphine treatment for initiation of individuals with opiate dependence into full-scale opioid maintenance treatment, and to study baseline predictors of successful transfer to full-scale treatment. METHODS: Interim treatment was introduced in a high-threshold setting with waiting lists to opioid maintenance treatment. Consecutive patients on the waiting list were offered the option to enter interim treatment. The interim program was a medication-only condition with supervised daily doses of buprenorphine-naloxone. The main outcome was successful transfer to full-scale opioid maintenance treatment, which required a drug-free urine sample. RESULTS: Forty-four patients entered interim buprenorphine treatment. Among them, 57% (n = 25) were successfully transferred to full-scale treatment after an average of 44 days. Remaining patients could not be transferred, generally because they did not manage to become drug-free. Successful transfer to full-scale treatment was associated with a lower baseline Alcohol Use Disorders Identification Test (AUDIT) score (4.4 vs. 12.6; P < .001) and tended to be associated with lower cannabis use (5.2 vs. 10.4 days during the past 30 days; P = .06) and lower heroin use (7.2 vs. 9.9 days; P = .09) prior to baseline. In a logistic regression analysis, only lower AUDIT score predicted successful treatment entry. CONCLUSIONS: According to these pilot data, supervised buprenorphine-naloxone in a medication-only interim treatment condition appears to be a feasible way to improve treatment initiation in a high-threshold setting. Polydrug use, including higher levels of alcohol consumption, may predict a more complicated course in interim treatment.

Interim treatment: Bridging delays to opioid treatment access.

OBJECTIVE: Despite the undisputed effectiveness of agonist maintenance for opioid dependence, individuals can remain on waitlists for months, during which they are at significant risk for morbidity and mortality. To mitigate these risks, the Food and Drug Administration in 1993 approved interim treatment, involving daily medication+emergency counseling only, when only a waitlist is otherwise available. We review the published research in the 20years since the approval of interim opioid treatment. METHODS: A literature search was conducted to identify all randomized trials evaluating the efficacy of interim treatment for opioid-dependent patients awaiting comprehensive treatment. RESULTS: Interim opioid treatment has been evaluated in four controlled trials to date. In three, interim treatment was compared to waitlist or placebo control conditions and produced greater outcomes on measures of illicit opioid use, retention, criminality, and likelihood of entry into comprehensive treatment. In the fourth, interim treatment was compared to standard methadone maintenance and produced comparable outcomes in illicit opioid use, retention, and criminal activity. CONCLUSIONS: Interim treatment significantly reduces patient and societal risks when conventional treatment is unavailable. Further research is needed to examine the generality of these findings, further enhance outcomes, and identify the patient characteristics which predict treatment response.

Extended pilot test of a cross-injection in situ denitrification system for pre-emptive treatment of municipal well water.

Elevated groundwater nitrate concentrations have been linked to deleterious health and environmental effects. A significant source of the nitrate is nitrogen fertilizers applied to agricultural landscapes. Beneficial Management Practices (BMPs), including the optimization of fertilizer use and selective crop rotations, have proven to be effective in some cases. The city of Woodstock in southern Ontario relies on public wells for all of its municipal supply. Several of the wells have experienced chronic increases in nitrate concentrations exceeding the maximum allowable limit of 10 mg/L N-NO3-. While BMPs are established, an interim reduction plan based on enhanced in situ denitrification (Cross Injection System, CIS) in a 15 m thick zone of high nitrate mass flux within the aquifer zone was evaluated. Based in the results of preliminary acetate injection experiments, a C:N ratio of 2.35, (approximately 260 mg acetate/L), was selected to optimize the denitrification reaction. Injections were performed for six hours a day every day for a period of approximately two months. Dissolved oxygen (DO) and nitrate concentrations recorded over time indicated that reduction of both commenced within a few days of the beginning of the acetate injections and reduced levels were maintained for the remainder of the two-month injection period. Denitrification occurred throughout the profile although nitrate reduction was the highest in the lower groundwater velocity zones. An overall reduction of nitrate of 50% was achieved through the treated section of the aquifer. It is estimated that an upscaled treatment system utilizing a treatment width of only 70 m would be sufficient to reduce the nitrate concentrations to below the drinking water limit demonstrating the potential for the CIS method to functions as an interim groundwater nitrate reduction strategy.

Within-subject evaluation of interim buprenorphine treatment during waitlist delays.

BACKGROUND: The effectiveness of opioid agonist treatment for opioid use disorder (OUD) is well established, and delays to treatment are still common, particularly in rural geographic areas. In a randomized 12-week pilot study, we demonstrated initial efficacy of a technology-assisted Interim Buprenorphine Treatment (IBT) vs. continued waitlist control (WLC) for reducing illicit opioid use and other risk behaviors during waitlist delays. Upon completion of that parent trial, WLC participants were given the opportunity to receive 12 weeks of IBT, permitting an additional within-subject examination of IBT effects. METHODS: Sixteen WLC participants crossed over to receive IBT, involving buprenorphine maintenance with bi-monthly visits, medication administration at home via a computerized device, daily monitoring calls using an Interactive Voice Response (IVR) phone system, and IVR-generated random call-backs. Biochemically-verified illicit opioid abstinence, changes in psychosocial functioning, and HIV + HCV knowledge were examined among participants originally randomized to the WLC phase and who subsequently crossed over to IBT (IBTc). RESULTS: Participants submitted a higher percentage of illicit opioid negative specimens at Weeks 4, 8, and 12 during IBT (75 %, 63 %, and 50 %) vs. WLC (0%, 0%, and 0%), respectively (p's<.01). Participants also demonstrated improvements in anxiety, depression, and HIV and HCV knowledge (p's<.01). Medication administration, daily IVR call and random call-back adherence and treatment satisfaction were also favorable. CONCLUSIONS: This within-subject evaluation provides additional support for interim buprenorphine's efficacy in reducing illicit opioid use and improving health outcomes during waitlist delays for more comprehensive treatment.

Predictive value of baseline 18F-FDG PET/CT and interim treatment response for the prognosis of patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy.

The present study aimed to investigate the prognostic value of baseline 18F-FDG PET/CT quantitative parameters and interim treatment response, and to assess whether the combination of these could improve the predictive efficacy in patients with diffuse large B-cell lymphoma (DLBCL) receiving R-CHOP chemotherapy. PET/CT images and clinical data of 64 patients with DLBCL who had undergone 18F-FDG PET/CT scan before and after 3 or 4 cycles of R-CHOP chemotherapy were retrospectively reviewed. The quantitative parameters including standardized uptake value (SUV), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter of the maximum lesion (Dmax) were measured on baseline PET/CT images. Cox proportional hazards model was used to evaluate the influence of baseline PET/CT parameters, clinical indicators and interim treatment response on prognosis. Survival analysis was performed using Kaplan-Meier method. Receiver operating characteristic (ROC) curve analysis was performed to estimate the predictive efficacy of the combination of baseline PET/CT parameters and interim treatment response. Ann Arbor stage, International Prognostic Index (IPI), lactate dehydrogenase (LDH), necrosis, MTVmax, TLGmax, Dmax and interim treatment response showed association with 2-year progression-free survival (PFS, P<0.05). LDH, necrosis, MTVmax, MTVsum, TLGmax, TLGsum, Dmax and interim treatment response showed association with 2-year overall survival (OS, P<0.05). Ann Arbor stage, Dmax and interim treatment response were found to be independent predictors of 2-year PFS (P<0.05), while Dmax and interim treatment response were found to be independent predictors of 2-year OS (P<0.05). The PFS and OS curves of Dmax <5.7 cm group and Dmax ≥5.7 cm group, complete response (CR) group and non-CR group were significantly different, respectively (P<0.05). The baseline 18F-FDG PET/CT parameters and interim treatment response have important prognostic values in DLBCL patients who received R-CHOP chemotherapy. Combined application of Dmax and interim treatment response improved the predictive efficacy of 2-year PFS. It may be helpful to identify patients who are at high-risk of relapse and to guide early clinical intervention of these patients.

Effects of Interim Buprenorphine Treatment for opioid use disorder among emerging adults.

OBJECTIVE: Although opioid maintenance is a first-line approach for treating opioid use disorder (OUD), suboptimal treatment outcomes have been reported among emerging adults (EAs; 18-25 years of age). In this secondary analysis, we compared treatment outcomes between EAs and older adults (OAs; ≥ 26 years of age) receiving low-barrier, technology-assisted Interim Buprenorphine Treatment (IBT) during waitlist delays to comprehensive opioid maintenance treatment. METHOD: Participants were 35 individuals with OUD who received IBT consisting of 12-weeks of buprenorphine maintenance with bi-monthly clinic visits and technology-assisted monitoring. At monthly follow-up assessments, participants completed staff-observed urinalysis, the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), and Addiction Severity Index (ASI). RESULTS: At study intake, EAs (n = 10) reported greater past-year intravenous drug use and greater employment, legal, and psychiatric severity (p's < .05) compared to OAs (n = 25). Despite these initial differences, there were no significant differences in the percentages of urine specimens testing negative for illicit opioids between EA and OA participants at Study Week 4 (90 % vs. 88 %, p = .99), Week 8 (80 % vs. 76 %, p = .99) or Week 12 (60 % vs. 68 %, p = .71). Relative to their older peers, EAs also demonstrated significantly greater improvements on the BAI, BDI-II, and ASI Employment and Legal subscales (p's < .05). CONCLUSIONS: Despite presenting with greater past-year intravenous drug use and psychosocial severity relative to OAs, EAs responded favorably to the IBT intervention.

Bridging waitlist delays with interim buprenorphine treatment: initial feasibility.

Despite the effectiveness of agonist maintenance for opioid dependence, individuals can remain on waitlists for months, during which they are at significant risk for morbidity and mortality. Interim dosing, consisting of daily medication without counseling, can reduce these risks. In this pilot study, we examined the initial feasibility of a novel technology-assisted interim buprenorphine treatment for waitlisted opioid-dependent adults. Following buprenorphine induction during Week 1, participants (n=10) visited the clinic at Weeks 2, 4, 6, 8, 10 and 12 to ingest their medication under staff observation, provide a urine specimen and receive their remaining doses via a computerized Med-O-Wheel Secure device. They also received daily monitoring via an Interactive Voice Response (IVR) platform, as well as random call-backs for urinalysis and medication adherence checks. The primary outcome was percent of participants negative for illicit opioids at each 2-week visit, with secondary outcomes of past-month drug use, adherence and acceptability. Participants achieved high levels of illicit opioid abstinence, with 90% abstinent at the Week 2 and 4 visits and 60% at Week 12. Significant reductions were observed in self-reported past-month illicit opioid use (p<.001), opioid withdrawal (p<.001), opioid craving (p<.001) and ASI Drug composite score (p=.008). Finally, adherence with buprenorphine administration (99%), daily IVR calls (97%) and random call-backs (82%) was high. Interim buprenorphine treatment shows promise for reducing patient and societal risks during delays to conventional treatment. A larger-scale, randomized clinical trial is underway to more rigorously examine the efficacy of this treatment approach.