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).

Drug and alcohol use in Iraq: findings of the inaugural Iraqi Community Epidemiological Workgroup.

BACKGROUND: Reports suggest increased use of alcohol, prescription drugs, and illicit drugs in Iraq in the past decade, which may portend an increase in substance use disorders (SUDs) and, thus, an increased need for treatments. OBJECTIVES/METHODS: To develop better information on the nature and extent of drug and alcohol use in Iraq, the Iraqi Ministry of Health, with support from the US government and technical assistance from US researchers, held an initial Iraqi Community Epidemiology Work Group meeting in May 2012 in Baghdad. Drug seizure data were the primary data source, provided by Iraqi law enforcement and customs officials. Ministry of Health officials presented data from hospitals (medical and psychiatric), outpatient clinics, and health centers, as well as from surveys of medical patients, pharmacy patients, and prisoners. RESULTS: The data suggest that the most commonly used substances are alcohol, hashish, and prescription drugs. New drugs in Iraq's drug use scene include the amphetamine-type substances "Captagon" and crystal methamphetamine, and the painkiller tramadol. Seizures of Captagon, methamphetamine, Afghan opium, teriac (a crude form of opium), and heroin at border crossings may indicate that these substances are becoming more popular. A plan for an ongoing program of CEWG meetings was developed. CONCLUSIONS: Drug and alcohol use in Iraq is increasing and new drugs are appearing in the country. An ongoing program for monitoring drug use trends and informing Iraqi policy makers is important for public health planning, including the development of strategies to identify citizens with SUDs and provide them treatment.

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.

Expanding access to treatment for stimulant use disorder in a frontier state: A qualitative study of contingency management and TRUST program implementation in Montana.

BACKGROUND: The client population eligible for treatment services supported by State Opioid Response (SOR) grant funding, administered by the Substance Abuse and Mental Health Services Administration (SAMHSA), was expanded to include individuals with a stimulant use disorder (stimUD) in 2020. Due to a significant need to improve services for individuals with stimUD in Montana, the Behavioral Health and Developmental Disabilities Division (BHDD) of the Montana Department of Public Health and Human Services used the grant opportunity to work with experts in the field of stimUD to pilot contingency management (CM) and the Treatment for Individuals who Use Stimulants (TRUST) treatment model. The CM protocol included twice weekly visits for twelve weeks, using an escalating schedule of gift card incentives contingent upon stimulant-negative urine samples. TRUST is a multi-component treatment program, incorporating exercise, group therapy, and individual therapy with content guided by cognitive behavioral therapy (CBT) and clinical research associate (CRA) materials. In addition to SOR dollars, BHDD used additional funding for CM reinforcers provided by state tax dollars to meet research-supported target incentive totals. METHODS: In this pilot project, TRUST/CM was implemented by four state-approved treatment providers and three Federally Qualified Health Centers (FQHCs), all of which had little prior experience with CM as a component of their treatment programs for stimUD. This article examines the processes of training staff, the experiences among staff with initial implementation of the treatment model, and the client characteristics of initial pilot treatment cohorts. Data for this study include primary qualitative data collected from providers, as well as client characteristics collected on the SAMHSA Government Performance and Results Act (GPRA) data collection form. RESULTS: Seven sites were trained in TRUST/CM, and these sites enrolled a total of 70 patients in the program. Qualitative data collected through interviews with site staff revealed the following themes: the value of intensive technical assistance being integrated in the program, concerns about staff retention and loss of expertise, adjustments of target client populations, and the importance of creative strategies for the provision of evidence-informed incentive totals. CONCLUSIONS: TRUST/CM was implemented throughout Montana, including rural and urban communities. Qualitative and quantitative data support that providers viewed the CM component as beneficial for treatment retention and improved outcomes for people with stimUD. These implementation study results provide insight into challenges and solutions for providers who are considering the implementation of CM within either a state-approved substance use treatment clinic or FQHC.

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.

Correlates of hospitalization for alcohol-using methadone-maintained persons with physical health problems.

This cross-sectional study (n = 190) examined correlates of hospitalization for physical health problems among methadone maintenance therapy (MMT) clients with a history of alcohol abuse. The study was derived from baseline data collected for a longitudinal trial assessing the effect of motivational interviewing among alcohol-abusing adults undergoing MMT. The sample included clients who were 18-55 years of age, abusing alcohol, and receiving MMT from five large methadone maintenance clinics in the Los Angeles area. A structured questionnaire was used to collect the data. Correlates of hospitalization in logistic regression analysis included lack of social support, recent victimization, age of first alcohol use, chronic severe pain in the previous 6 months, not having children, and ethnicity. Identification of hospitalization risk factors among alcohol-abusing MMT clients is a first step to developing risk-reducing interventions designed to lower hospitalization rates in this population.

Self-reported substance use in Iraq: findings from the Iraqi National Household Survey of Alcohol and Drug Use, 2014.

AIMS: To estimate the prevalence of tobacco, alcohol and drug use in Iraq using data from the Iraqi National Household Survey of Alcohol and Drug Use (INHSAD). DESIGN: A cross-sectional survey was conducted using a multi-stage cluster sampling method. Trained surveyors conducted face-to-face household interviews. SETTING: Iraq, from April 2014 to December 2014. PARTICIPANTS: A total of 3200 adult, non-institutionalized Iraqi citizens residing across all 18 governorates of Iraq. MEASUREMENTS: We estimated weighted prevalence and 95% confidence intervals (CIs) for life-time, past-year and past-month use of a variety of substances (tobacco, alcohol, prescription drugs and illicit drugs). For each substance, we also estimated whether individuals knew people who currently use the substance. FINDINGS: Self-reported past-month tobacco use was 23.2% (95% CI = 21.40, 25.19). Past-month alcohol use was 3.2% (95% CI = 2.58, 3.93). Women reported significantly lower prevalence for both tobacco and alcohol use compared with men (P-value < 0.01 for both). Only 1.4% (95% CI = 0.67, 3.02) reported past-month non-medical use of any prescription drugs. None of the women reported using any illicit drugs, and only 0.2% (95% CI = 0.07, 0.49) of men reported using any illicit drugs in the past month. Approximately 90.5% (95% CI = 88.58, 92.11) knew someone who uses tobacco, 42.4% (95% CI = 39.53, 45.24) knew someone who drinks alcohol, 27.9% (95% CI = 25.53, 30.45) knew someone who uses medication outside a doctor's instructions and 9.2% (95% CI = 7.87, 10.75) knew someone who uses an illicit drug. CONCLUSIONS: Psychoactive drug use is generally low in Iraq, tobacco being highest at an estimated 23.2%. Iraqi women report significantly less substance use than Iraqi men, which may be related to cultural gender norms. Discrepancy between self-report and 'knowing someone who uses a substance' suggests under-reporting in this population.

Testing and linkage to HIV care in China: a cluster-randomised trial.

BACKGROUND: Multistage, stepwise HIV testing and treatment procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete engagement of patients along the care cascade translates into high preventable mortality. We aimed to identify whether a structural intervention to streamline testing and linkage to HIV health care would improve testing completeness, ART initiation, and viral suppression and reduce mortality. METHODS: We did a cluster-randomised, controlled trial in 12 hospitals in Guangxi, China. All hospitals were required to be level 2A county general hospitals and ART delivery sites. We selected the 12 most similar hospitals in terms of structural characteristics, past patient caseloads, and testing procedures. Hospitals were randomly assigned (1:1) to either the One4All intervention or standard of care. Hospitals were randomised in a block design and stratified by the historical rate of testing completeness of the individual hospital during the first 6 months of 2013. We enrolled patients aged 18 years or older who were identified as HIV-reactive during screening in study hospitals, who sought inpatient or outpatient care in a study hospital, and who resided in the study catchment area. The One4All strategy incorporated rapid, point-of-care HIV screening and CD4 counts, and in-parallel viral load testing, to promote fast and complete diagnosis and staging and provide immediate ART to eligible patients. Participants in control hospitals received standard care services. All enrolled patients were assessed for the primary outcome, which was testing completeness within 30 days, defined as completion of three required tests and their post-test counselling. Safety assessments were hospital admissions for the first 90 days and deaths up to 12 months after enrolment. This trial is registered with ClinicalTrials.gov, number NCT02084316. FINDINGS: Between Feb 24 and Nov 25, 2014, we enrolled 478 patients (232 in One4All, 246 in standard of care). In the One4All group, 177 (76%) of 232 achieved testing completeness within 30 days versus 63 (26%) of 246 in the standard-of-care group (odds ratio 19·94, 95% CI 3·86-103·04, p=0·0004). Although no difference was observed between study groups in the number of hospital admissions at 90 days, by 12 months there were 65 deaths (28%) in the in the One4All group compared with 115 (47%) in the standard-of-care group (Cox proportional hazard ratio 0·44, 0·19-1·01, p=0·0531). INTERPRETATION: Our study provides strong evidence for the benefits of a patient-centred approach to streamlined HIV testing and treatment that could help China change the trajectory of its HIV epidemic, and help to achieve the goal of an end to AIDS. FUNDING: US National Institute on Drug Abuse Clinical Trials Network and China's National Health and Family Planning Commission.

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.

Loss to Follow-Up from HIV Screening to ART Initiation in Rural China.

BACKGROUND: Patients who are newly screened HIV positive by EIA are lost to follow-up due to complicated HIV testing procedures. Because this is the first step in care, it affects the entire continuum of care. This is a particular concern in rural China. OBJECTIVE(S): To assess the routine HIV testing completeness and treatment initiation rates at 18 county-level general hospitals in rural Guangxi. METHODS: We reviewed original hospital HIV screening records. Investigators also engaged with hospital leaders and key personnel involved in HIV prevention activities to characterize in detail the routine care practices in place at each county. RESULTS: 699 newly screened HIV-positive patients between January 1 and June 30, 2013 across the 18 hospitals were included in the study. The proportion of confirmatory testing across the 18 hospitals ranged from 14% to 87% (mean of 43%), and the proportion of newly diagnosed individuals successfully initiated antiretroviral treatment across the hospitals ranged from 3% to 67% (mean of 23%). The average interval within hospitals for individuals to receive the Western Blot (WB) and CD4 test results from HIV positive screening (i.e. achieving testing completion) ranged from 14-116 days (mean of 41.7 days) across the hospitals. The shortest interval from receiving a positive EIA screening test result to receiving WB and CD4 testing and counseling was 0 day and the longest was 260 days. CONCLUSION: The proportion of patients newly screened HIV positive that completed the necessary testing procedures for HIV confirmation and received ART was very low. Interventions are urgently needed to remove barriers so that HIV patients can have timely access to HIV/AIDS treatment and care in rural China.

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.

Achieving cannabis cessation -- evaluating N-acetylcysteine treatment (ACCENT): design and implementation of a multi-site, randomized controlled study in the National Institute on Drug Abuse Clinical Trials Network.

Despite recent advances in behavioral interventions for cannabis use disorders, effect sizes remain modest, and few individuals achieve long-term abstinence. One strategy to enhance outcomes is the addition of pharmacotherapy to complement behavioral treatment, but to date no efficacious medications targeting cannabis use disorders in adults through large, randomized controlled trials have been identified. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) is currently conducting a study to test the efficacy of N-acetylcysteine (NAC) versus placebo (PBO), added to contingency management, for cannabis cessation in adults (ages 18-50). This study was designed to replicate positive findings from a study in cannabis-dependent adolescents that found greater odds of abstinence with NAC compared to PBO. This paper describes the design and implementation of an ongoing 12-week, intent-to-treat, double-blind, randomized, placebo-controlled study with one follow-up visit four weeks post-treatment. Approximately 300 treatment-seeking cannabis-dependent adults will be randomized to NAC or PBO across six study sites in the United States. The primary objective of this 12-week study is to evaluate the efficacy of twice-daily orally-administered NAC (1200 mg) versus matched PBO, added to contingency management, on cannabis abstinence. NAC is among the first medications to demonstrate increased odds of abstinence in a randomized controlled study among cannabis users in any age group. The current study will assess the cannabis cessation efficacy of NAC combined with a behavioral intervention in adults, providing a novel and timely contribution to the evidence base for the treatment of cannabis use disorders.

A comparison of buprenorphine taper outcomes between prescription opioid and heroin users.

OBJECTIVES: Dependence on prescription opioids (PO) is a growing problem. Although most research with buprenorphine has focused on heroin-dependent populations, we hypothesize that individuals dependent on PO display characteristics that may predict different outcomes in treatment, particularly in short-term taper procedures in which comorbidities such as pain conditions may complicate taper. METHODS: This secondary data analysis examined differences in outcomes between PO users (n = 90) and heroin users (n = 426) after a buprenorphine taper. Data were collected in a multisite randomized clinical trial conducted by the National Drug Abuse Treatment Clinical Trials Network at 11 study sites across the United States. After a 4-week buprenorphine induction/stabilization phase, 516 opioid-dependent individuals were randomized into 1 of 2 taper lengths (7 vs 28 days) to assess the association between taper length and outcome. The primary outcome was measured by urine drug test for opioids at the end of the taper period. Craving, withdrawal, and buprenorphine dose were also examined. RESULTS: After controlling for baseline demographic and drug use differences between the opioid use groups, results indicate that a higher percentage of the PO group (49%) provided an opioid-free urine drug specimen at the end of taper compared with the heroin group (36%; χ(2)(1) = 6.592, P < 0.010). CONCLUSION: Short-term taper is not recommended as a stand-alone treatment; however, patients may taper from buprenorphine as part of a treatment plan. Despite greater comorbidity, PO users seem to have favorable taper outcomes compared with heroin users. Further studies are required to examine longer-term treatment outcomes.

Cocaine use reduction with buprenorphine (CURB): rationale, design, and methodology.

BACKGROUND: Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. METHODS: This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. CONCLUSIONS: This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP.

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.

Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial.

CONTEXT: No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. OBJECTIVE: To evaluate the efficacy of brief and extended buprenorphine hydrochloride-naloxone hydrochloride treatment, with different counseling intensities, for patients dependent on prescription opioids. DESIGN: Multisite, randomized clinical trial using a 2-phase adaptive treatment research design. Brief treatment (phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week postmedication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. SETTING: Ten US sites. Patients A total of 653 treatment-seeking outpatients dependent on prescription opioids. INTERVENTIONS: In both phases, patients were randomized to standard medical management (SMM) or SMM plus opioid dependence counseling; all received buprenorphine-naloxone. MAIN OUTCOME MEASURES: Predefined "successful outcome" in each phase: composite measures indicating minimal or no opioid use based on urine test-confirmed self-reports. RESULTS: During phase 1, only 6.6% (43 of 653) of patients had successful outcomes, with no difference between SMM and SMM plus opioid dependence counseling. In contrast, 49.2% (177 of 360) attained successful outcomes in phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (phase 2, week 24) dropped to 8.6% (31 of 360), again with no counseling difference. In secondary analyses, successful phase 2 outcomes were more common while taking buprenorphine-naloxone than 8 weeks after taper (49.2% [177 of 360] vs 8.6% [31 of 360], P < .001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower phase 2 success rates while taking buprenorphine-naloxone. CONCLUSIONS: Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of an unsuccessful outcome is high, even in patients receiving counseling in addition to SMM.

A multi-site, two-phase, Prescription Opioid Addiction Treatment Study (POATS): rationale, design, and methodology.

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age > or =18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study.

From research to the real world: buprenorphine in the decade of the Clinical Trials Network.

The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphine's therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts.

Buprenorphine tapering schedule and illicit opioid use.

AIMS: To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. DESIGN: This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. SETTING: Eleven out-patient treatment programs in 10 US cities. INTERVENTION: Non-blinded dosing with Suboxone during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. MEASUREMENTS: The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. FINDINGS: At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). CONCLUSION: For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper.