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.).

Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

PURPOSE: The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). METHODS: Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. RESULTS: In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. CONCLUSION: These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Efficacy and safety of a monthly buprenorphine depot injection for opioid use disorder: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: RBP-6000, referred to as BUP-XR (extended-release buprenorphine), is a subcutaneously injected, monthly buprenorphine treatment for opioid use disorder. BUP-XR provides sustained buprenorphine plasma concentrations to block drug-liking of abused opioids over the entire monthly dosing period, while controlling withdrawal and craving symptoms. Administration of BUP-XR in a health-care setting also mitigates abuse, misuse, diversion, and unintentional exposure. We aimed to investigate the efficacy of different BUP-XR dosing regimens in participants with opioid use disorder. METHODS: This randomised, double-blind, placebo-controlled, phase 3 trial was done at 36 treatment centres in the USA. Treatment-seeking adults aged 18-65 years who had moderate or severe opioid use disorder (as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) entered an open-label run-in phase of up to 2 weeks' treatment with buprenorphine-naloxone sublingual film. Eligible participants were then randomly assigned (4:4:1:1) with an interactive voice/web-response system to receive BUP-XR 300 mg/300 mg (six injections of 300 mg), BUP-XR 300 mg/100 mg (two injections of 300 mg plus four injections of 100 mg), or volume-matched placebo every 28 days, and received weekly individual drug counselling. No supplemental buprenorphine was allowed. The primary efficacy endpoint was participants' percentage abstinence from opioid use, defined as the percentage of each participant's negative urine samples and self-reports of illicit opioid use from week 5 to week 24, analysed in the full analysis set. Safety was assessed in all participants who received at least one dose of BUP-XR or placebo. This study is registered with ClinicalTrials.gov, number NCT02357901. FINDINGS: From Jan 28, 2015, to Nov 12, 2015, 1187 potential participants were screened, 665 entered run-in, and 504 received BUP-XR 300 mg/300 mg (n=201), BUP-XR 300 mg/100 mg (n=203), or placebo (n=100). Mean participants' percentage abstinence was 41·3% (SD 39·7) for BUP-XR 300 mg/300 mg and 42·7% (38·5) for 300 mg/100 mg, compared with 5·0% (17·0) for placebo (p<0·0001 for both BUP-XR regimens). No compensatory non-opioid drug use was observed during BUP-XR treatment. The most common adverse events were headache (17 [8%] participants in the BUP-XR 300 mg/300 mg group vs 19 [9%] participants in the BUP-XR 300 mg/100 mg group vs six [6%] participants in the placebo group), constipation (16 [8%] vs 19 [9%] vs 0), nausea (16 [8%] vs 18 [9%] vs five [5%]), and injection-site pruritis (19 [9%] vs 13 [6%] vs four [4%]). The BUP-XR safety profile was consistent with other buprenorphine products for treatment of opioid use disorder, except for injection-site reactions, which were reported in more than 5% of all participants who received BUP-XR, but were mostly mild and not treatment-limiting. INTERPRETATION: Participants' percentage abstinence was significantly higher in both BUP-XR groups than in the placebo group. Treatment with BUP-XR was also well tolerated. The availability of this monthly formulation, delivered by health-care providers, represents an advance in treatment for opioid use disorder that enhances the benefits of buprenorphine by delivering sustained, optimal exposure, while reducing risks of current buprenorphine products. FUNDING: Indivior.

Buprenorphine Maintenance Subjects Are Hyperalgesic and Have No Antinociceptive Response to a Very High Morphine Dose.

Objective: Acute pain management in opioid-dependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Design: Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations. Setting: Ambulatory. Subjects: Twelve buprenorphine-maintained subjects: once daily sublingual dose (range = 2-22 mg); no dose change for 1.5-12 months. Ten healthy controls. Methods: Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times. Results: Cold pressor responses (seconds): baseline: control 34 ± 6 vs buprenorphine 17 ± 2 (P = 0.009); morphine infusion-end: control 52 ± 11(P = 0.04), buprenorphine 17 ± 2 (P > 0.5); electrical stimulation responses (volts): baseline: control 65 ± 6 vs buprenorphine 53 ± 5 (P = 0.13); infusion-end: control 74 ± 5 (P = 0.007), buprenorphine 53 ± 5 (P > 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P = 0.03); infusion-end: control 15 (P = 0.09), buprenorphine 12 (P < 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 ± 1, buprenorphine 136 ± 10. Conclusions: Buprenorphine subjects, compared with controls, were hyperalgesic (cold pressor test), did not experience antinociception, despite high plasma morphine concentrations, and experienced respiratory depression. Clinical implications are discussed.

Sex differences in opioid use and medical issues during buprenorphine/naloxone treatment.

BACKGROUND: There are sex differences in buprenorphine/naloxone clinical trials for opioid use. While women have fewer opioid-positive urine samples, relative to men, a significant decrease in opioid-positive samples was found during treatment for men, but not women. In order to inform sex-based approaches to improve treatment outcomes, research is needed to determine if opioid use, and predictors of opioid use, differs between men and women during treatment. OBJECTIVES: To test for sex differences in opioid use during a buprenorphine/naloxone clinical trial and determine if sex differences exist in the associations between addiction-related problem areas and opioid use over the course of the trial. METHOD: This secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003 examined sex differences (men = 347, women = 169) in opioid-positive samples in a randomized clinical trial comparing 7-day vs. 28-day buprenorphine/naloxone tapering strategies. Addiction-related problem areas were defined by Addiction Severity-Lite (ASI-L) domain composite scores. RESULTS: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial (B = .33, p = .01) and medical issues were positively related to submitting an opioid-positive sample during treatment for women (B = 1.67, p = .01). No ASI-L domain composite score was associated with opioid-positive samples during treatment for men. CONCLUSION: Women were more likely than men to use opioids during the course of the buprenorphine/naloxone clinical trial, and medical issues predicted opioid use during treatment for women but not men. Complementary treatment for medical problems during opioid replacement therapy may benefit women.

Care cascade structural intervention versus standard of care in the diagnosis and treatment of HIV in China: a cluster-randomized controlled trial protocol.

BACKGROUND: The high rate of attrition along the care cascade of infection with human immunodeficiency virus (HIV) results in lost opportunities to provide timely antiretroviral therapy (ART) and to prevent unnecessarily high mortality. This study aims to assess the effectiveness of a structural intervention, the one-stop ("One4All") strategy that streamlines China's HIV care cascade with the intent to improve testing completeness, ART initiation, viral suppression, and mortality. METHOD: A two-arm, cluster-randomized controlled trial was implemented in twelve county hospitals in Guangxi China to test the effectiveness of the One4All strategy (intervention arm) compared to the current standard of care (SOC; control arm). The twelve study hospitals were selected for homogeneity and allocated one-to-one to the intervention and control arms. All patients screening HIV positive in study hospitals were enrolled. Target study enrollment was 180 participants per arm, 30 participants per hospital. Basic demographic information was collected as well as HIV risk behavior and route of infection. In intervention hospitals, patients then went on to receive point-of-care CD4 testing and in-parallel viral load (VL) testing whereas patients in control hospitals progressed through the usual SOC cascade. The primary outcome measure was testing completeness within 30 days of positive initial HIV screening result. Testing completeness was defined as receipt of all tests, test results, and post-test counseling. The secondary outcome measure was ART initiation (receipt of first ART prescriptions) within 90 days of positive initial HIV screening result. Tertiary outcome measures were viral suppression (≤200 copies/mL) and all-cause mortality at 12 months. DISCUSSION: We expect that this first-ever, cluster-randomized controlled trial of a bundle of interventions intended to streamline the HIV care cascade in China (the One4All strategy) will provide strong evidence for the benefit of accelerating diagnosis, thorough clinical assessment, and ART initiation via an optimized HIV care cascade. We furthermore anticipate that this evidence will be valuable to policymakers looking to elevate China's overall HIV/AIDS response to meet the UNAIDS 90-90-90 targets and the broader, global goal of eradication of the HIV/AIDS epidemic. TRIAL REGISTRATION: ClinicalTrials.gov # NCT02084316 . (Registered on March 7, 2014).

The relationship between primary prescription opioid and buprenorphine-naloxone induction outcomes in a prescription opioid dependent sample.

BACKGROUND AND OBJECTIVES: This analysis aims to: (1) compare induction experiences among participants who self-reported using one of the four most commonly reported POs, and (2) examine factors associated with difficult bup-nx induction. Our hypothesis, based on previous research and current guidelines, is that those on longer-acting opioids will have experienced more difficult inductions. METHODS: The Prescription Opioid Addiction Treatment Study (POATS) was a multi-site, randomized clinical trial, using a two-phase adaptive treatment research design. This analysis examines bup-nx induction of participants who self-reported primary PO use of methadone, ER-oxycodone, IR-oxycodone, and hydrocodone (n = 69). Analyses examined characteristics associated with difficult induction, defined as increased withdrawal symptoms measured by the Clinical Opiate Withdrawal Scale (COWS) after the first bup-nx dose with higher scores denoting greater withdrawal symptoms/severity. RESULTS: Contrary to our hypothesis, difficult induction experiences did not differ by primary PO type. Those who experienced a post-induction increase in COWS score had lower pre-dose COWS scores compared to those who did not experience a post-induction increase in COWS score (10.09 vs. 12.77, t(624) = -13.56, p < .001). Demographics characteristics, depression, and pain history did not predict a difficult induction. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Difficult bup-nx inductions were not associated with participants' primary PO. Severity of withdrawal, measured with the COWS, was an important variable, reminding clinicians that bup-nx should not be commenced prior to evidence of moderate opioid withdrawal. These findings add to the evidence that with careful procedures, bup-nx can used with few difficulties in PO-dependent patients. (Am J Addict 2014;23:343-348).

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.

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings.

BACKGROUND: This analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE). METHODS: The RECOVER (Remission From Chronic Opioid Use: Studying Environmental and Socioeconomic Factors on Recovery) study recruited participants from BUP-XR clinical trials (NCT02357901, NCT025100142, and NCT02896296) to assess whether there were sustained benefits after leaving the trial. Abstinence from opioids and from all illicit substances (excluding medical cannabis), health-related quality of life, depression, and employment were measured after BUP-XR discontinuation and change in outcomes assessed at 6, 12, and 18 months. Results were analyzed within the full cohort and by duration of BUP-XR treatment (0-2 months, 3-5 months, 6-11 months, 12 months, or 13-18 months) with and without inverse probability weights adjusting for differences in baseline characteristics. RESULTS: Of 533 participants, 529 were assessed over the 18-month study period. Further posttrial pharmacotherapy was reported by 33% of participants. At RECOVER baseline, longer BUP-XR was associated with higher abstinence (0-2 months BUP-XR [n = 116]: 38.8%; 3-5 months BUP-XR [n = 61]: 41.0%; 6-11 months BUP-XR [n = 86]: 68.6%; 12 months BUP-XR [n = 135]: 71.9%; 18 months BUP-XR [n = 131]: 88.2%) and greater 12-Item Short Form Health Survey mental component scores. Over 60% of participants had stable or improved outcomes at 6, 12, and 18 months assessments. Overall 47% of participants self-reported sustained opioid abstinence for the full 18-month follow-up, with greater sustained abstinence associated with longer BUP-XR treatment duration. A sensitivity analysis, removing patients receiving medications for OUD, yielded similar results. CONCLUSIONS: Participants from BUP-XR clinical trials who continued into RECOVER maintained or improved on numerous outcomes over 18 months, demonstrating the long-term positive impact of OUD pharmacotherapy.

Psychometric properties of the Treatment Effectiveness Assessment in methamphetamine use disorder.

INTRODUCTION: The ability for people living with stimulant use disorder to live meaningful lives requires not only abstinence from addictive substances, but also healthy engagement with their community, lifestyle practices, and overall health. The Treatment Effectiveness Assessment (TEA) assesses components of recovery consisting of four functional domains: substance use, health, lifestyle, and community. This secondary data analysis of 403 participants with severe methamphetamine use disorder tested the reliability and validity of the TEA. METHODS: Participants were enrolled in the Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for methamphetamine use disorder. The study used total TEA and domain scores at baseline to assess factor structure and internal consistency, as well as construct validity related to substance cravings (visual analog scale [VAS]), quality of life (quality-of-life assessment [QoL]), mental health (Patient Health Questionnaire-9 [PHQ-9], Concise Health Risk Tracking Scale Self-Report [CHRT-SR16]), and social support (CHRT-SR16). RESULTS: Individual TEA items showed moderate to large correlations with each other (r = 0.27-0.51; p < .001), and strong correlations to the total score (r = 0.69-0.78; p < .001). Internal consistency was strong (coefficient α = 0.73 [0.68-0.77]; coefficient ω = 0.73 [0.69-0.78]). Construct validity was acceptable, with the strongest correlation between the TEA Health item and the general health status item on the QoL (r = 0.53, p < .001). CONCLUSIONS: TEA has acceptable levels of reliability and validity supporting prior similar findings in a sample of participants with moderate to severe methamphetamine use disorder. Results from this study provide support for its use in assessing clinically meaningful changes beyond simply reduced substance use.

Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial.

BACKGROUND: Opioid dependence is associated with low rates of treatment-seeking, poor adherence to treatment, frequent relapse, and major societal consequences. We aimed to assess the efficacy, safety, and patient-reported outcomes of an injectable, once monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification. METHODS: We did a double-blind, placebo-controlled, randomised, 24-week trial of patients with opioid dependence disorder. Patients aged 18 years or over who had 30 days or less of inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX or placebo by an interactive voice response system, stratified by site and gender in a centralised, permuted-block method. Participants also received 12 biweekly counselling sessions. Participants, investigators, staff , and the sponsor were masked to treatment allocation. The primary endpoint was the response profile for confirmed abstinence during weeks 5­24, assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported opioid-free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00678418. FINDINGS: Between July 3, 2008, and Oct 5, 2009, 250 patients were randomly assigned to XR-NTX (n=126) or placebo (n=124). The median proportion of weeks of confirmed abstinence was 90·0% (95% CI 69·9­92·4) in the XR-NTX group compared with 35·0% (11·4­63·8) in the placebo group (p=0·0002). Patients in the XR-NTX group self-reported a median of 99·2% (range 89·1­99·4) opioid-free days compared with 60·4% (46·2­94·0) for the placebo group (p=0·0004). The mean change in craving was ­10·1 (95% CI ­12·3 to ­7·8) in the XR-NTX group compared with 0·7 (­3·1 to 4·4) in the placebo group (p<0·0001). Median retention was over 168 days in the XR-NTX group compared with 96 days (95% CI 63­165) in the placebo group (p=0·0042). Naloxone challenge confirmed relapse to physiological opioid dependence in 17 patients in the placebo group compared with one in the XR-NTX group (p<0·0001). XR-NTX was well tolerated. Two patients in each group discontinued owing to adverse events. No XR-NTX-treated patients died, overdosed, or discontinued owing to severe adverse events. INTERPRETATION: XR-NTX represents a new treatment option that is distinct from opioid agonist maintenance treatment. XR-NTX in conjunction with psychosocial treatment might improve acceptance of opioid dependence pharmacotherapy and provide a useful treatment option for many patients. FUNDING: Alkermes.

Health-related quality of life changes associated with buprenorphine treatment for opioid dependence.

BACKGROUND: Few studies have described improvement in health-related quality of life (HRQOL) associated with opioid dependence treatment with buprenorphine (ODT-B). OBJECTIVE: To evaluate HRQOL changes in domain scores, physical and mental component summaries, and health utilities (HUs) associated with ODT-B using the Short Form 36 (SF-36). METHODS: We assessed HRQOL changes in a substudy of a pharmacokinetic study that compared buprenorphine oral tablet and liquid dosage formulations over 16 weeks. Individuals, aged 18-65 years, were screened for opioid dependence. They were excluded if they would not agree to birth control or had a serious medical condition. Subjects received psychosocial counseling and weekly group therapy. The SF-36 was administered upon enrollment and at 4-week intervals. We used the SF-6D to estimate HUs. We performed intention to treat (ITT) analyses based on the last observation available for each subject. Paired t tests of each domain and HU, limited to remaining patients at each 4-week interval, were also conducted. RESULTS: Of 96 subjects enrolled, cumulative dropouts over time resulted in 80, 69, 59, and 44 subjects remaining at 4, 8, 12, and 16 weeks. There were no significant differences in opioid-positive urines, dropout rates, or dosage changes between formulations. In the ITT analyses, HRQOL improvements over time were bodily pain (62.1 vs. 69.1, P = 0.017), vitality (49.8 vs. 56.5, P = 0.001), mental health (59.9 vs. 66.0, P = 0.001), social function (66.4 vs. 74.7, P = 0.001), role emotional (59.4 vs. 71.9, P = 0.003), role physical (60.9 vs. 70.6, P = 0.005), and mental component summary (41.9 vs. 45.4, P<0.001). HU scores also improved (0.674 vs. 0.715, P = 0.001). Results from paired t tests, with only concurrently enrolled patients, showed similar improvements from baseline to 4, 8, 12, or 16 weeks. CONCLUSION: Buprenorphine, accompanied with psychosocial counseling, was associated with improved HRQOL and HUs.

HIV/AIDS and drug use in China--interactions, impacts, and issues.

The interrelationships of HIV/AIDS and drug use and misuse result in complex problems that have been addressed by a variety of sociolegal approaches that often are in contrast to evidence-based medical practices proven effective in reducing associated harms. Like other countries struggling to reduce the incidence and consequences of addiction and HIV/AIDS, China is working to improve systems of care and to revise policies toward drug use and misuse and HIV/AIDS. Greater interaction with researchers and clinicians from around the world can foster increased awareness of effective practices and help implement effective strategies to deal with the problems of HIV/AIDS, and addiction.

Participant characteristics and buprenorphine dose.

BACKGROUND: Clinical parameters for determining buprenorphine dose have not been adequately examined in treatment outcome research. OBJECTIVES: This study is a secondary analysis of data collected in a recently completed comparison of buprenorphine taper schedules conducted as part of the National Institute on Drug Abuse's Clinical Trials Network to assess whether participant baseline characteristics are associated with buprenorphine dose. METHODS: After 3 weeks of flexible dosing, 516 participants were categorized by dose provided in the final dosing week (9.3% received a final week dose of 8 mg buprenorphine, 27.3% received 16 mg, and 63.4% received 24 mg). RESULTS: Findings show that final week dose groups differed in baseline demographic and drug use characteristics including education, heroin use, route of drug administration, withdrawal symptoms, and craving. These groups also differed in opioid use during the four dosing weeks, with the lowest use in the 8 mg group and highest use in the 24 mg group (p < .0001). Additional analyses address withdrawal symptoms and craving. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Final week dose groups differed in demographic and drug use characteristics, and the group receiving the largest final week dose had the highest rate of continued opioid use. These findings may contribute to the development of clinical guidelines regarding buprenorphine dose in the treatment of opioid dependence; however, further investigations that include random assignment to dose by baseline characteristics are needed.

Comparative profiles of men and women with opioid dependence: results from a national multisite effectiveness trial.

BACKGROUND: Accumulating evidence indicates important gender differences in substance use disorders. Little is known, however, about gender differences and opioid use disorders. OBJECTIVES: To compare demographic characteristics, substance use severity, and other associated areas of functioning (as measured by the Addiction Severity Index-Lite (ASI-Lite)) among opioid-dependent men and women participating in a multisite effectiveness trial. METHODS: Participants were 892 adults screened for the National Institute on Drug Abuse Clinical Trials Network investigation of the effectiveness of two buprenorphine tapering schedules. RESULTS: The majority of men and women tested positive for oxycodone (68% and 65%, respectively) and morphine (89% each). More women than men tested positive for amphetamines (4% vs. 1%, p < .01), methamphetamine (11% vs. 4%, p < .01), and phencyclidine (8% vs. 4%, p = .02). More men than women tested positive for methadone (11% vs. 6%, p = .05) and marijuana (22% vs. 15%, p = .03). Craving for opioids was significantly higher among women (p < .01). Men evidenced higher alcohol (p < .01) and legal (p = .04) ASI composite scores, whereas women had higher drug (p < .01), employment (p < .01), family (p < .01), medical (p < .01), and psychiatric (p < .01) ASI composite scores. Women endorsed significantly more current and past medical problems. CONCLUSIONS: Important gender differences in the clinical profiles of opioid-dependent individuals were observed with regard to substance use severity, craving, medical conditions, and impairment in associated areas of functioning. The findings enhance understanding of the characteristics of treatment-seeking men and women with opioid dependence, and may be useful in improving identification, prevention, and treatment efforts for this challenging and growing population.

Depressive symptoms, substance use, and HIV-related high-risk behaviors among opioid-dependent individuals: results from the Clinical Trials Network.

The sample included 343 opioid-dependent adults enrolled in two national multisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-002). Opioid-dependent individuals were recruited from 12 sites across the United States from January 2001 to July 2002. We examined associations between depressive symptoms, co-occurring substance use (i.e., the use of substances other than opioids), and HIV-related sexual and injection risk behaviors. Data were collected using the Addiction Severity Index and the HIV Risk Behavior Scale, and analyzed using linear regression. Depressive symptoms were associated with an increased level of injection risk behaviors but were not associated with risky sexual behaviors. The co-occurring use of amphetamines also increased the likelihood of risky sexual behaviors. The study limitations and clinical implications are noted. The study was funded by the U.S. National Institute on Drug Abuse.

Conducting clinical research with prescription opioid dependence: defining the population.

Most treatment studies of opioid-dependent populations have focused predominantly on heroin users, despite a recent increase in those dependent upon prescription opioids. A key methodological challenge involved in studying the latter group involves defining the population. Specifically, researchers must decide whether to include (1) concurrent heroin users and (2) individuals with pain. The multi-site Prescription Opioid Addiction Treatment Study is examining treatments for this population. This paper describes various inclusion criteria considered by the study team related to heroin use and pain. The goal was to recruit a distinct but generalizable population of individuals dependent upon prescription opioids. (Am J Addict 2010;00:1-6).

United Nations Office on Drugs and Crime International Network of Drug Dependence Treatment and Rehabilitation Resource Centres: Treatnet.

Key to the dissemination of evidence-based addiction treatments is the exchange of experiences and mutual support among treatment practitioners, as well as the availability of accurate addiction training materials and effective trainers. To address the shortage of such resources, the United Nations Office on Drugs and Crime (UNODC) created Treatnet, a network of 20 drug dependence treatment resource centers around the world. Treatnet's primary goal is to promote the use of effective addiction treatment practices. Phase I of this project included (1) selecting and establishing a network of geographically distributed centers; (2) conducting a capacity-building program consisting of a training needs assessment, development of training packages, and the training of 2 trainers per center in 1 content area each; and (3) creating good-practice documents. Data on the training activities conducted by the trainers during their first 6 months in the field are presented. Plans for Phase II of the Treatnet project are also discussed.

Buprenorphine implants for treatment of opioid dependence: a randomized controlled trial.

CONTEXT: Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms. OBJECTIVE: To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants. INTERVENTION: After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients. MAIN OUTCOME MEASURE: The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24. RESULTS: The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the clinician global ratings of improvement (P < .001) than those who received placebo implants. Minor implant site reactions were the most common adverse events: 61 patients (56.5%) in the buprenorphine group and 29 (52.7%) in the placebo group. CONCLUSION: Among persons with opioid dependence, the use of buprenorphine implants compared with placebo resulted in less opioid use over 16 weeks as assessed by urine samples. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00447564.