Usability and feasibility of a take-home methadone web-application for opioid treatment program patients: A Small Business Innovation Research mixed methods study.

BACKGROUND: Most patients in opioid treatment programs (OTPs) attend daily for observed dosing. A Stage IA (create and adapt) and a Stage IB (feasibility and pilot) mixed method studies tested a web-application (app) designed to facilitate access to take-home methadone. METHODS: A Stage IA, intervention development study, used qualitative interviews to assess the usability (ease of use) and feasibility (ability to implement) of a take-home methadone app. The Stage IA market research was a two-week test with 96 patient participants from four OTPs. Qualitative interviews were completed with 20 systematically selected individuals who used the take-home app and 20 OTP clinicians (five each from the four OTPs). The Stage IB Small Business Innovation Research (SBIR) study (24 patients and 8 clinicians in a single OTP) included quantitative assessments of the app's usability, acceptability, appropriateness, and feasibility. Thematic analysis coded participant and staff assessments of the take-home app. RESULTS: Stage IA patients (mean age = 41 years; 52 % men, 57 % White) and IB patients (mean age = 38 years, 54 % men, 79 % White) described the app as "easy to use." Compared to unsupervised take-homes, some patients preferred using the take-home app. In Stage IB, patients rated the app highly on standardized measures of usability, acceptability, appropriateness, and feasibility. Clinician ratings were more ambivalent. Patients rated in-clinic dosing as more disruptive than unsupervised take-homes and take-homes using the app. DISCUSSION: A Stage IA study informed the development and maturation of a Stage IB feasibility pilot study. Overall, the take-home app's usability, acceptability, appropriateness, and feasibility were rated positively. Clinical staff ratings were less positive, but individuals commented that using the app a) enhanced patient quality of life, b) provided new tools for counselors, and c) offered competitive advantages. The SBIR award enhanced market research with more complete and systematic data collection and analysis.

Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder.

BACKGROUND: BUP-XR (SUBLOCADE®) is the first buprenorphine extended-release subcutaneous injection approved in the USA for monthly treatment of moderate-to-severe opioid use disorder (OUD). Among patients with OUD, those who inject or use high doses of opioids likely require higher doses of buprenorphine to maximize treatment efficacy. The objective of this analysis was to compare the efficacy and safety of 100-mg versus 300-mg maintenance doses of BUP-XR in OUD patients who inject opioids. METHODS: This was a secondary analysis of a randomized, double-blind, placebo-controlled study in which adults with moderate or severe OUD received monthly injections of BUP-XR (2 × 300-mg doses, then 4 × 100-mg or 300-mg maintenance doses) or placebo for 24 weeks. Abstinence was defined as opioid-negative urine drug screens combined with negative self-reports collected weekly. Each participant's percentage abstinence was calculated after the first, second, and third maintenance doses in opioid-injecting and non-injecting participants. The proportion of participants achieving opioid abstinence in each group was also calculated weekly. Treatment retention rate following the first maintenance dose was estimated for opioid-injecting participants with Kaplan-Meier method. Risk-adjusted comparisons were made via inverse propensity weighting using propensity scores. Buprenorphine plasma concentration-time profiles were compared between injecting and non-injecting participants. The percentages of participants reporting treatment-emergent adverse events were compared between maintenance dose groups within injecting and non-injecting participants separately. RESULTS: BUP-XR 100-mg and 300-mg maintenance doses were equally effective in non-injecting participants. However, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements over the 100-mg maintenance dose for treatment retention and opioid abstinence. Exposure-response analyses confirmed that injecting participants would require higher buprenorphine plasma concentrations compared to non-injecting opioid participants to achieve similar efficacy in terms of opioid abstinence. Importantly, both 100- and 300-mg maintenance doses had comparable safety profiles, including hepatic safety events. CONCLUSIONS: These analyses show clear benefits of the 300-mg maintenance dose in injecting participants, while no additional benefit was observed in non-injecting participants relative to the 100-mg maintenance dose. This is an important finding as opioid-injecting participants represent a high-risk and difficult-to-treat population. Optimal buprenorphine dosing in this population might facilitate harm reduction by improving abstinence and treatment retention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02357901.

Recruitment challenges for a prospective telehealth cohort study.

Background: The COVID-19 pandemic presents challenges in participant recruitment strategies for clinical research involving people with opioid use disorders recently engaged in treatment. We describe challenges to participant recruitment in a trial comparing virtual buprenorphine treatment platform to office-based buprenorphine treatment. Methods: The parent study was a cohort trial of telehealth delivered buprenorphine treatment compared to office-based buprenorphine treatment, however, due to the pandemic potential participant recruitment for both arms became virtual. Between 9/27/2021 and 7/11/2022, telephone, email, flyers, and word-of-mouth were used to recruit study participants from each treatment setting. Recruitment tracking documents recorded the primary outcomes: number of outreach attempts and most effective contact methods. Results: Treatment settings provided contact information for 1485 potential study participants. Information was incorrect or disconnected for 282 (19%) individuals, 695 (47%) did not respond to outreach, and 508 (34%) responded to outreach. Of these responders, 369 were interested in study participation, 259 completed the online informed consent and screening assessment, and 148 met eligibility criteria and enrolled in the study. A total of 3804 virtual outreach attempts across 1485 potential participants were made, resulting in an average of 2.7 attempts per contact and a mean of 25.7 attempts per enrolled participant (n = 148). Conclusion: Conducting research during the COVID-19 pandemic required shifting from in-person to virtual recruitment strategies to contact and engage potential study participants. Virtual recruitment for this population during a pandemic appears to be less efficient and hindered efforts to meet recruitment goals.

Patient evaluation of a smartphone application for telehealth care of opioid use disorder.

BACKGROUND: People with opioid use disorder (OUD) face barriers to entering and remaining in life-saving treatment (e.g., stigma, detrimental interactions with health care, and privacy concerns). Telehealth and related technology can reduce barriers to entering and staying in care. Patient feedback is critical to the development of these newer treatment approaches to ensure they are usable and do not inadvertently recreate treatment barriers. PURPOSE: Evaluate the perceived usability of existing and planned features of a mobile application (app) that facilitates delivery of OUD treatment via telehealth. METHODS: People with current or prior experience with OUD treatment were eligible for the study. Participants (n = 31; 55% women) provided feedback on an interactive prototype demonstration via individual qualitative interviews and completed a quantitative survey on the app's perceived usability. Descriptive statistics summarized the usability survey. We analyzed qualitative interview transcripts to elicit common themes. RESULTS: Participants were primarily white (77%) with a mean age of 42.2 years (range 22-69). Participants rated the six major features of the current app as helpful (median response 5 out of 5) and appreciated the flexibility of conducting a visit from a place of their choosing. Participants regarded the five proposed components of the app, such as daily affirmations and medication treatment-related reminders (e.g., pick up medication at pharmacy, medication schedule), as useful features with medians 5 out of 5, and reported they would recommend the app to others for OUD care. Participant qualitative interviews provided additional information on perceived usability of existing and proposed app features. CONCLUSION: Our study suggests that an appealing, easy-to-use app-with tools and features that effectively support care-could circumvent existing barriers and foster sustained recovery.

Assessment of craving in opioid use disorder: Psychometric evaluation and predictive validity of the opioid craving VAS.

BACKGROUND: This work evaluated the psychometric properties of the single-item Opioid Craving Visual Analog Scale (OC-VAS) for opioid use disorder (OUD). METHODS: Psychometric evaluation of the OC-VAS (range: 0-100 mm) was supported by Subjective Opiate Withdrawal Scale (SOWS) item 16 and total score, Clinical Opiate Withdrawal Scale (COWS) scores, and the 36-Item Short-Form Health Survey, using data from phase 3 study (NCT02357901; N = 487) participants who received randomized treatment and completed the OC-VAS at screening. Descriptive properties, test-retest reliability, construct validity, known-groups validity, and responsiveness were assessed. Interpretation of meaningful change and predictive validity were also explored. RESULTS: Descriptive properties for the OC-VAS at screening did not provide evidence of problematic floor/ceiling effects or missingness. The test-retest reliability was established by weekly intraclass correlations >0.70. At the screening and end of the study, the strong positive correlations between OC-VAS and SOWS Total/Item 16 score and the significant OC-VAS differences among COWS severity groups supported construct validity and known-groups (discriminating ability) validity, respectively. The associations between the changes in OC-VAS and in supporting measures/opioid use from screening to the end of the study demonstrated responsiveness and the ability to detect change in clinical status. During the induction and randomization treatment periods, significant relationships were identified between OC-VAS score and subsequent opioid use. CONCLUSIONS: This psychometric evaluation of the OC-VAS performed on a large OUD patient population provides evidence to support its use to measure the severity of opioid craving and its ability to predict opioid use.

Bupropion and Naltrexone in Methamphetamine Use Disorder.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Increasing substance use disorder counselors' self-efficacy and skills in talking to patients about sex and HIV risk: A randomized training trial.

BACKGROUND: People with substance use disorder (SUD) experience increased risk for HIV, Hepatitis C, and sexually transmitted illnesses via risky sex. This high-risk population would benefit from sexual risk reduction interventions integrated into SUD treatment. However, many SUD counselors report lack of skill or confidence in addressing sexual risk with patients. METHODS: This study was part of a larger nested 2 × 2 factorial repeated measures design, which compared two levels of counselor training (Basic-2 h versus Enhanced-10 h plus ongoing coaching). We determined whether counselors receiving Enhanced training addressing their motivation, confidence and skills (a) increased knowledge about sexual issues; (b) increased self-efficacy to discuss sex with patients; and (c) improved skills in discussing sex as part of SUD treatment, compared with those receiving shorter information-based training. Counselors providing individual therapy at two opioid treatment programs (OTP) and two psychosocial outpatient programs in the United States were eligible. Randomization occurred after Basic training. Measures included self-report (self-efficacy and knowledge) and blinded coding of standardized patient interviews (skill). RESULTS: Counselors receiving Enhanced training (n = 28) showed significant improvements compared to their Basic training counterparts (n = 32) in self-efficacy, use of reflections, and use of decision-making and communication strategies with standardized patients. These improvements were maintained from post-training to 3-month follow-up. No adverse effects of study participation were reported. CONCLUSIONS: Results suggest that counselors can improve their knowledge, self-efficacy and skill related to sexual risk conversations with patients based on modest skills-based training.

Counselor turnover in substance use disorder treatment research: Observations from one multisite trial.

Background: Counselor workforce turnover is a critical area of concern for substance use disorder (SUD) treatment providers and researchers. To facilitate the adoption and implementation of innovative treatments, attention must be paid to how SUD treatment workforce issues affect the implementation of clinical effectiveness research. Multiple variables have been shown to relate to turnover, yet reasons that are specific to conducting research have not been systematically assessed. Methods: In a randomized clinical trial testing a sexual risk reduction counselor training intervention, 69 counselors at 4 outpatient SUD treatment sites (2 opioid treatment programs [OTPs], 2 psychosocial) were enrolled and randomized to 1 of 2 training conditions (Standard vs. Enhanced). Study counselor and agency turnover rates were calculated. Agency context and policies that impacted research participation were examined. Results: Study turnover rates for enrolled counselors were substantial, ranging from 33% to 74% over approximately a 2-year active study period. Study counselor turnover was significantly greater at outpatient psychosocial programs versus OTPs. Counselor turnover did not differ due to demographic or training condition assignment. Leaving agency employment was the most typical reason for study counselor turnover. Conclusions: This secondary analysis used data from a multisite study with frontline counselors to provide a qualitative description of challenges faced when conducting effectiveness research in SUD treatment settings. That counselors may be both subjects and deliverers of the interventions studied in clinical trials, with implications for differential impact on study implementation, is highlighted. We offer suggestions for researchers seeking to implement effectiveness research in SUD clinical service settings.

A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.

BACKGROUND: Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. METHODS: In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. RESULTS: There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. CONCLUSIONS: In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study.

AIMS: To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. METHODS: This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events. RESULTS: No group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events. CONCLUSIONS: Buprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial.

AIMS: To compare long-term outcomes among participants randomized to buprenorphine or methadone. DESIGN, SETTING AND PARTICIPANTS: Follow-up was conducted in 2011-14 of 1080 opioid-dependent participants entering seven opioid treatment programs in the United States between 2006 and 2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24 weeks; 795 participants completed in-person interviews (~74% follow-up interview rate) covering on average 4.5 years. MEASUREMENTS: Outcomes were indicated by mortality and opioid use. Covariates included demographics, site, cocaine use and treatment experiences. FINDINGS: Mortality was not different between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone [42.8 versus 31.7% positive opioid urine specimens, P < 0.01, effect size (h) = 0.23 (0.09, 0.38); 5.8 days versus 4.4 days of past 30-day heroin use, P < 0.05, effect size (d) = 0.14 (0.00, 0.28)]. Opioid use during the follow-up period by randomization condition was also significant (F(7,39,600) = 3.16; P < 0.001) due mainly to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine. CONCLUSIONS: There are few differences in long-term outcomes between buprenorphine and methadone treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in opioid use.

Massage Impact on Pain in Opioid-dependent Patients in Substance Use Treatment.

BACKGROUND: Chronic pain is a common cause of health care utilization and high levels of pain are pronounced in individuals engaged in methadone maintenance treatment. Although massage has been demonstrated to alleviate chronic pain symptoms, its use as an adjunctive therapy to modify pain during opioid-replacement treatment is absent from the literature. PURPOSE: To consider the efficacy of Swedish massage in reducing pain in opioid-dependent patients with chronic pain receiving methadone treatment. SETTING: Trial was conducted at a nonprofit methadone treatment center serving low-income patients. RESEARCH DESIGN: A randomized clinical trial with randomized to either 1) massage plus treatment-as-usual (TAU) (n = 27) or 2) TAU (n = 24). Durability of treatment effect was evaluated at Week 12. INTERVENTION: Eight weekly 50-minute Swedish massage sessions plus TAU or TAU alone. MAIN OUTCOME MEASURES: Pain, anxiety, depression, physical functioning, decreased substance use, and improvement in treatment engagement. RESULTS: Randomized participants were comparable at Baseline for demographic, pain, physical, and emotional variables. Massage group reported improved pain scores; worst pain had a clinically significant 2-point improvement while the other pain scores did not. Overall improvements were not observed in treatment engagement or levels of anxiety, depression, or physical functioning. A subgroup of the participants, who felt they could be pain-free, consistently reported improvements in pain from Baseline to Week 8, and this was most pronounced and clinically significant in the massage group. CONCLUSIONS: These preliminary findings do not support an overall clinically significant positive effect of Swedish massage on reduction in pain ratings or improvement in anxiety, depression, or treatment engagement in a substance-using, opioid-dependent population with chronic pain. Future nonpharmacologic pain research in marginalized substance-using populations may wish to consider some of the challenges and limitations faced in this project.

Alcohol Screening among Opioid Agonist Patients in a Primary Care Clinic and an Opioid Treatment Program.

Problem alcohol use is associated with adverse health and economic outcomes, especially among people in opioid agonist treatment. Screening, brief intervention, and referral to treatment (SBIRT) are effective in reducing alcohol use; however, issues involved in SBIRT implementation among opioid agonist patients are unknown. To assess identification and treatment of alcohol use disorders, we reviewed clinical records of opioid agonist patients screened for an alcohol use disorder in a primary care clinic (n = 208) and in an opioid treatment program (n = 204) over a two-year period. In the primary care clinic, 193 (93%) buprenorphine patients completed an annual alcohol screening and six (3%) had elevated AUDIT scores. In the opioid treatment program, an alcohol abuse or dependence diagnosis was recorded for 54 (27%) methadone patients. Practitioner focus groups were completed in the primary care (n = 4 physicians) and the opioid treatment program (n = 11 counselors) to assess experience with and attitudes towards screening opioid agonist patients for alcohol use disorders. Focus groups suggested that organizational, structural, provider, patient, and community variables hindered or fostered alcohol screening. Alcohol screening is feasible among opioid agonist patients. Effective implementation, however, requires physician training and systematic changes in workflow.

A Preliminary Study Examining Nutritional Risk Factors, Body Mass Index, and Treatment Retention in Opioid-Dependent Patients.

Poor nutritional health among opioid-dependent individuals is well established, yet no nutritional screening tool exists for this specific population. The utility of "Determine Your Nutritional Health" developed by the Nutrition Screening Initiative is considered. The study examines the questionnaire's relevance in patients beginning opioid dependence treatment at a methadone-assisted treatment program (N = 140) by examining nutritional risk factor prevalence, body mass index, and association between nutritional risk level and treatment retention. The majority of patients reported at least one nutritional risk factor (89 %) and 59 % were at high nutritional risk. Body mass index was not related to nutritional risk; however, a trend was identified between increasing nutritional risk and decreased retention in treatment. These preliminary findings suggest the need for incorporation of nutritional screening at intake in opioid treatment programs, consideration of the effect of dietary risk on treatment retention, and the potential utility of this screening tool.

Patient perspectives on buprenorphine/naloxone: a qualitative study of retention during the starting treatment with agonist replacement therapies (START) study.

This study examines the barriers and facilitators of retention among patients receiving buprenorphine/naloxone at eight community-based opioid treatment programs across the United States. Participants (n = 105) were recruited up to three and a half years after having participated in a randomized clinical trial comparing the effect of buprenorphine/naloxone and methadone on liver function. Semi-structured interviews were conducted with 67 patients provided with buprenorphine/naloxone who had terminated early and 38 patients who had completed at least 24 weeks of the trial. Qualitative data were analyzed using the constant comparison method. Barriers to buprenorphine/naloxone retention that emerged included factors associated with: (1) the design of the clinical trial; (2) negative medication or treatment experience; and (3) personal circumstances. The facilitators comprised: (1) positive experience with the medication; (2) personal determination and commitment to complete; and (3) staff encouragement and support. The themes drawn from interviews highlight the importance of considering patients' prior experience with buprenorphine/naloxone and methadone, medication preference, personal circumstances, and motivation to abstain from illicit use or misuse of opioids, as these may influence retention. Ongoing education of patients and staff regarding buprenorphine/naloxone, especially in comparison to methadone, and support from staff and peers are essential.

Pain and emotional distress among substance-use patients beginning treatment relative to a representative comparison group.

OBJECTIVES: A secondary analysis assessed health-related quality-of-life (HRQOL) characteristics (ie, anxiety, depression, fatigue, and types of pain) among patients entering substance-use treatment and identified characteristics specific to treatment modalities relative to a representative comparison group. METHODS: As part of a larger alcohol bank assessment, substance-use patients (n = 406) beginning methadone treatment (n = 170) or other outpatient treatment (n = 236) and a comparison group representative of the general population (n = 1000) completed a survey measuring anxiety, depression, fatigue, pain interference, and pain in the last 7 days. Previous studies lacked comparable and concurrent assessments across these 3 groups. RESULTS: Patients entering substance-use treatment had relatively high levels of emotional distress and poorer HRQOL relative to the general population. Among treatment modalities, patients beginning methadone treatment reported the highest levels of pain interference and pain behavior and the poorest physical functioning. Before the potentially modifying effects of methadone maintenance, patients beginning agonist therapy reported the greatest levels of compromised quality of life. CONCLUSIONS: These data present the magnitude of differences in HRQOL characteristics between treatment and comparison groups using the same assessment rubric and may help inform the design and timing of treatment modalities, thereby enhancing treatment efficacy for patients.

Extended-release naltrexone for alcohol and opioid dependence: a meta-analysis of healthcare utilization studies.

Through improved adherence, once-monthly injectable extended-release naltrexone (XR-NTX) may provide an advantage over other oral agents approved for alcohol and opioid dependence treatment. The objective of this study was to evaluate cost and utilization outcomes between XR-NTX and other pharmacotherapies for treatment of alcohol and opioid dependence. Published studies were identified through comprehensive search of two electronic databases. Studies were included if they compared XR-NTX to other approved medicines and reported economic and healthcare utilization outcomes in patients with opioid or alcohol dependence. We identified five observational studies comparing 1,565 patients using XR-NTX to other therapies over 6 months. Alcohol dependent XR-NTX patients had longer medication refill persistence versus acamprosate and oral naltrexone. Healthcare utilization and costs was generally lower or as low for XR-NTX-treated patients relative to other alcohol dependence agents. Opioid dependent XR-NTX patients had lower inpatient substance abuse-related utilization versus other agents and $8170 lower total cost versus methadone.

Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial.

AIMS: To examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence. DESIGN, SETTINGS AND PARTICIPANTS: This secondary analysis included 1267 opioid-dependent individuals participating in nine opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks. MEASUREMENTS: The analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24-week trial. FINDINGS: The treatment completion rate was 74% for MET versus 46% for BUP (P < 0.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60 mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30-32 mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower [odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.52-0.76, P < 0.01] among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (i) BUP [versus MET, hazard ratio (HR) = 1.61, CI = 1.20-2.15], (ii) lower medication dose (<16 mg for BUP, <60 mg for MET; HR = 3.09, CI = 2.19-4.37), (iii) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (iv) being younger, Hispanic and using heroin or other substances during treatment. CONCLUSIONS: Provision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids.

Buprenorphine/naloxone and methadone maintenance treatment outcomes for opioid analgesic, heroin, and combined users: findings from starting treatment with agonist replacement therapies (START).

OBJECTIVE: The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type (heroin, opioid analgesic [OA], or combined [heroin and OA]) and route (injector or non-injector) of opioid use. METHOD: A total of 1,269 participants (32.2% female) were randomized to receive one of two study medications (methadone or buprenorphine/naloxone [BUP]). Of these, 731 participants completed the 24-week active medication phase. Treatment outcomes were opioid use during the final 30 days of treatment (among treatment completers) and treatment attrition. RESULTS: Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users. Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors. Further, injectors were more likely to be using at end of treatment compared with non-injectors. OA users were more likely to complete treatment compared with heroin users and combined users. Non-injectors were more likely than injectors to complete treatment. There were no interactions between type of opioid used or injection status and treatment assignment (methadone or BUP) on either opioid use or treatment attrition. CONCLUSIONS: Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors. Irrespective of medication, heroin use and injecting are associated with treatment attrition and opioid misuse during treatment. These results have particular clinical interest, as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users.

Buprenorphine/Naloxone and methadone effects on laboratory indices of liver health: a randomized trial.

BACKGROUND: Buprenorphine/naloxone (BUP) and methadone (MET) are efficacious treatments for opioid dependence, although concerns about a link between BUP and drug-induced hepatitis have been raised. This study compares the effects of BUP and MET on liver health in opioid-dependent participants. METHODS: This was a randomized controlled trial of 1269 opioid-dependent participants seeking treatment at 8 federally licensed opioid treatment programs and followed for up to 32 weeks between May 2006 and August 2010; 731 participants met "evaluable" criteria defined as completing 24 weeks of medication and providing at least 4 blood samples for transaminase testing. Participants were randomly assigned to receive BUP or MET for 24 weeks. Shift table analysis determined how many evaluable participants moved between categories of low and elevated transaminase levels. Predictors of moving from low to high transaminase levels were identified. RESULTS: Changes in transaminase levels did not differ by medication condition. Baseline infection with hepatitis C or B was the only significant predictor of moving from low to elevated transaminase levels; 9 BUP and 15 MET participants showed extreme liver test elevations and were more likely than those without extreme elevations to have seroconverted to both hepatitis B and C during the study, or to use illicit drugs during the first 8 weeks of treatment. MET participants were retained longer in treatment than BUP participants. CONCLUSIONS: This study demonstrated no evidence of liver damage during the initial 6 months of treatment in either condition. Physicians can prescribe either medication without major concern for liver injury.