National Drug Abuse Treatment. Clinical Trials Network. Study Summaries

Transcription

1 National Drug Abuse Treatment Clinical Trials Network Study Summaries

2 CTN-0001 Buprenorphine/Naloxone (Bup/Nx) versus Clonidine for Inpatient Opiate Detoxification. For decades, clinicians have been frustrated by the inability to successfully detoxify opiate addicted patients because opiate-based detoxification, one of the most effective means to achieving that goal, has been unavailable outside the very restrictive confines of narcotic treatment programs. Bup/Nx shows promise as an effective aid for opiate detoxification; however, little data have been generated for the shorter-term use of Bup/Nx for this indication. Because the diversity of clinics in the CTN provides an unparalleled opportunity to conduct such a clinical endeavor, the utility of Bup/Nx in short term (13 day) detoxification versus clonidine in an inpatient setting was tested in the CTN. Primary Findings: A total of 59 of the 77 (77%) in-patients assigned to the Bup/Nx condition achieved the treatment success criterion compared to 8 of the 36 (22%) assigned to clonidine. The study supported the benefits of Bup/Nx for opioid detoxification in inpatient treatment programs and illustrated important ways in which clinical research can be conducted in community treatment programs. Dissemination: This CTN protocol was selected for development as a NIDA/SAMHSA Blending Team product. Reference 1 : Ling, W., et al. (2005). A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings for the National Institute on Drug Abuse Clinical Trials Network. Addiction 100: CTN-0002 Buprenorphine/Naloxone (Bup/Nx) versus Clonidine for Outpatient Opiate Detoxification. For decades clinicians, have been frustrated by the inability to successfully detoxify opiate addicted patients because opiate-based detoxification, one of the most effective means to achieving that goal, has been unavailable outside the very restrictive confines of narcotic treatment programs. Bup/Nx shows promise as an effective aid for opiate detoxification; however, little data have been generated for the shorter-term use of Bup/Nx for this indication. Because the diversity of clinics in the CTN provides an unparalleled opportunity to conduct such a clinical endeavor, the utility of buprenorphine/naloxone in short term (13 day) detoxification versus clonidine in an outpatient setting was tested in the CTN. Primary Findings: A total of 46 of the 157 (29%) outpatients assigned to Bup/Nx condition achieved the treatment success criterion, compared to 4 of the 74 (5%) assigned to clonidine. The study supported the benefits of Bup/Nx for opioid detoxification in outpatient treatment programs and illustrated important ways in which clinical research can be conducted in community treatment programs. Dissemination: This CTN protocol was selected for development as a NIDA/SAMHSA Blending Team product. Reference: Ling, W., et al. (2005). A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings for the National Institute on Drug Abuse Clinical Trials Network. Addiction 100: CTN-0003 Suboxone (Buprenorphine/Naloxone) Taper: A Comparison of Two Schedules. This study was undertaken to compare, in an outpatient setting, the relative advantage of two Suboxone (Bup/Nx) tapering schedules (one rapid and one gradual) following four weeks of Suboxone stabilization, as reflected by the proportion of participants providing opiate free urines at the end of the taper regimen. In total, 516 participants were randomized to one of two taper schedules, either 7 days or 28 days. The reason for conducting this study was not to advocate for short-term treatment, but to determine the relative ease of using a more rapid vs. a gradual taper should someone need to discontinue Bup/Nx. Primary Findings: There appears to be no advantage in prolonging the duration of the taper for individuals terminating Bup/Nx therapy for opioid dependence. At the end of 1 References listed here are for primary outcome papers ONLY. Other secondary analyses have been published on most completed trials. For additional information, visit the CTN dissemination library at

3 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, resp). Reference: Ling, W., et al. (2009). Buprenorphine tapering schedule and illicit opioid use. Addiction 104: CTN-0004 MET (Motivational Enhancement Treatment) To Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse. A considerable body of research has shown strong support for the usefulness of motivational interventions in initiating treatment and in reducing use of alcohol, cigarettes, and abused drugs. This study examined the effect of a treatment approach called Motivational Enhancement Treatment (MET), which is a manual-based treatment based on the principles of Motivational Interviewing in comparison to counseling-as-usual (CAU). The MET counselor evokes a person s intrinsic desire and ability to change drug use behaviors, rather than imposing a directive do this approach. Primary Findings: While clients in both treatment conditions reduced substance use during the 4-week treatment periods, clients whose treatment included MET were significantly more likely to sustain this reduced use over the 12-week follow-up, and the CAU clients increased their use during that time. In addition, this trial established a standard for MI training and delivery, and demonstrated the essential role played by clinical supervisors in ensuring effective treatment delivery, and a regimen of rigorous training and supervision in MI has been broadly accepted in the field. Reference: Ball, S., et al. (2007). Site Matters: Multisite randomized trial of motivational enhancement therapy in community drug abuse clinics. Journal of Consulting & Clinical Psychology 75 (4): CTN-0005 Motivational Interviewing (MI) To Improve Treatment Engagement and Outcome in Subjects Seeking Treatment for Substance Abuse. A considerable body of research has shown strong support for the usefulness of motivational interventions in initiating treatment and in reducing use of alcohol, cigarettes, and abused drugs. This study examined the effectiveness of integrating Motivational Interviewing (MI) techniques into the initial contact and evaluation session for substance users entering outpatient treatment across five community-based treatment settings. Clients were randomized to receive either the standard intake/evaluation session at each site, or an intake session in which MI techniques and strategies were integrated. Primary Findings: Participants assigned to MI had significantly better retention -- a key component of success -- through the 28-day follow-up than those assigned to the standard intervention. There were no significant effects of MI on substance use outcomes at either the 28-day or 84-day follow-up. Results suggest that communitybased clinicians can effectively implement MI when provided training and supervision, and that integrating MI techniques in the earliest phases of treatment may have positive effects on retention early in the course of treatment. Dissemination: This CTN protocol was selected for development as a NIDA/SAMHSA Blending Team product. Reference: Carroll, K., et al. (2006). Motivational interviewing to improve treatment engagement and outcome in individuals seeking treatment for substance abuse: A multisite effectiveness study. Drug & Alcohol Dependence 81: CTN-0006 Motivational Incentives for Enhanced Drug Abuse Recovery: Drug Free Clinics. To improve outcomes for treatment of drug abuse, it is necessary to use interventions that can motivate clients to attend treatment and initiate and sustain abstinence. This study in counseling-based drug-free clinics evaluated the effectiveness of abstinence-based incentives considerably lower in cost than those typically used in research clinics. The primary aim was to determine whether introduction

4 of abstinence-based incentives targeting (a) drug abstinence and (b) patient retention into usual care improves these treatment outcomes, compared to usual care alone. 415 cocaine or methamphetamine users from eight counseling-based outpatient drug-free clinics were randomly assigned to receive usual care plus abstinence-based incentives or to receive usual care alone for 12 weeks. Primary Findings: Patients assigned to the abstinence-based incentive condition remained in treatment longer and submitted a greater percentage of substance-free urine samples, compared to patients assigned to the usual care condition. Prizes cost on average $ 203 per patient, or $ 2.42 per patient per day. A lowcost abstinence-based procedure was effective in enhancing retention and drug-abstinence outcomes in counseling-based drug-free clinics. Dissemination: This CTN protocol was selected for development as a NIDA/SAMHSA Blending Team product. Reference: Petry, N., et al. (2005). Effect of prizebased incentives on outcomes in stimulant abusers in outpatient psychosocial treatment programs. Archives of General Psychiatry 62: CTN-0007 Motivational Incentives for Enhanced Drug Abuse Recovery: Methadone Clinics. To improve outcomes for treatment of drug abuse, it is necessary to use interventions that can motivate clients to attend treatment and initiate and sustain abstinence. This study in communitybased methadone-maintenance clinics evaluated the effectiveness of abstinence-based incentives considerably lower in cost than those typically used in research clinics. The primary aim was to determine whether introduction of abstinence-based incentives targeting (a) drug abstinence and (b) patient retention into usual care improves these treatment outcomes, compared to usual care alone. 388 stimulant-abusing patients enrolled in six methadone-maintenance community treatment programs for at least 1 month and no more than 3 years were randomly assigned to receive usual care plus abstinence-based incentives or to usual care alone for 12 weeks. Primary Findings: Patients assigned to the abstinence-based incentive condition were twice as likely to submit alcohol- and stimulant-free urine samples, compared to patients assigned to the usual care condition. Achieving up to 12 weeks of continuous abstinence was more likely for abstinence-based incentive versus usual care patients. Groups did not differ on study retention or counseling attendance. Prizes cost on average $ 120 per patient. A low-cost abstinence-based procedure was effective in improving stimulant-abstinence outcomes in community-based methadone-maintenance clinics. Dissemination: This CTN protocol was selected for development as a NIDA/SAMHSA Blending Team product. Reference: Peirce, J., et al. (2006). Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment. Archives of General Psychiatry 63: CTN-0007-A-1 Survey of Counselor s Perceptions of Incentive Programs (Ancillary study to CTN 0006/0007). In this study, counselors were recruited from eight MIEDAR treatment sites and seven matched non-miedar sites within the same CTN nodes, and asked to complete the Provider Survey on Incentives (PSI). Only non-miedar sites that had never participated in a formal incentives program were matched with the MIEDAR sites. Primary matching criteria were program modality (drug free or methadone outpatient) and program size as determined by number of counselors at the treatment program. The PSI solicits opinions about efficacy and limitations of incentive programs as well as philosophical/moral attitudes that might be a barrier to adoption. It has two scales: one for tangible incentives and one for social incentives. Both of these scales indicate the degree of positive (high score) or negative (low score) beliefs about incentive interventions. The hypotheses are: (1): Providers that have participated in an incentive program will have more positive endorsements and fewer concerns about incentive programs than will providers that have not used incentives; and (2): Providers will have more positive endorsements and fewer concerns about incentives programs that rely

5 on social reinforcers as compared to those that rely on tangible incentives. Status: Study completed and investigators are analyzing data for future publication. CTN-0007-A-2 Economic Evaluations in the CTN - Methods & Applications (Ancillary study to CTN 0004/0005/0007). Abstinence-based incentives have been shown to improve treatment outcomes over usual care alone in community-based drug abuse treatment programs, but their cost-effectiveness has not been examined. Economic analyses of cost-effectiveness are clinically important, as even if abstinence-based incentives are shown to be effective, they may have limited adoption within community-based treatment programs unless they are also shown to be cost-effective. Therefore, we undertook an economic study of multi-site CTN clinical trials that used to evaluate cost-effectiveness. Primary Findings: In both methadonemaintenance clinics and counseling-based drug-free clinics, abstinence-based incentives provided better treatment outcomes than usual care, but required additional costs. Compared to usual care in counseling-based drug-free clinics, the incremental cost of using abstinence-based incentives to lengthen the longest duration of continuous stimulant and alcohol abstinence by 1 week was $258, and to obtain an additional stimulant-free urine sample was $146. Compared to usual care in methadone-maintenance clinics, the incremental cost of using abstinence-based incentives to lengthen the longest duration of continuous stimulant and alcohol abstinence by 1 week was $141, and to obtain an additional stimulant-free urine sample was $70. Adding abstinence-based incentives to usual care was more cost-effective in methadone-maintenance clinics than in counseling-based drug-free clinics. Empirical analyses are needed to help policy makers decide whether abstinence-based incentives are worth the extra expense. References: (1) Olmstead, T., et.al. (2007). American Journal on Addiction 16(6) (2) Sindelar, J., et.al. (2007). Addiction 102(9) (3) Olsmtead, T., et.al. (2007). Drug & Alcohol Dependence 16 87(2-3) CTN-0008 A Baseline for Investigating Diffusion of Innovation. The Baseline Study was designed to help us better understand the Community Treatment Programs participating in the NIDA Clinical Trials Network (CTN). Using a series of surveys, the study sought to 1) describe the programs and practitioners delivering drug abuse treatment services within the CTN; 2) build a system that can track changes in program and staff characteristics; 3) allow treatment program managers to compare their program to others both within the CTN and nationwide; and 4)promote studies of organizational change and the characteristics that predict whether research-based treatment strategies will become part of usual treatment in a program. Primary Findings: The surveys describe 106 corporations (95% response rate) providing drug abuse treatment in 348 treatment units (91% response rate). Most treatment units are not-for-profit and are not affiliated with health care or mental health care organizations and tend to be larger than the modal drug abuse treatment program. In the CTN, hospital-based services are over-represented and programs based in mental health centers are underrepresented. The treatment units serve a heterogeneous patient population, and the inpatient, residential, methadone, and outpatient levels of care vary in the services provided. Reference: McCarty, D., et al. (2008). Treatment programs in the National Drug Abuse Treatment Clinical Trials Network. Drug & Alcohol Dependence 92: CTN-0009 Smoking Cessation Treatment with Transdermal Nicotine Replacement Therapy in Substance Abuse Rehabilitation Programs. Nicotine dependence is common among drug and alcohol dependent patients. This multi-site trial evaluated the effectiveness of smokingcessation treatment with transdermal nicotine patch replacement (SC) as an adjunct to treatment-as-

6 usual for illicit substance abuse (TAU). Cigarette smokers from five methadone-maintenance clinics and two drug and alcohol dependence treatment programs were randomly assigned to receive either SC as an adjunct to usual care or TAU. SC consisted of 1 week of group counseling before the target quit date and 8 weeks of group counseling plus transdermal nicotine patch replacement treatment after the target quit date. Primary Findings: Smoking abstinence rates in the SC group were greater during treatment and at the 13- and 26-week follow-up visits, compared to the usual care group. Also, the SC group exhibited greater reductions in cigarettes smoked per day, cigarette craving, nicotine withdrawal, and exhaled carbon monoxide levels, compared to the usual care group. SC did not differ from TAU on abstinence from the primary substance of abuse, rates of retention in substance abuse treatment, and craving for primary substance of abuse. Compliance with SC was moderate at best, and was positively associated with rates of smoking abstinence. Smoking cessation treatment improved smoking abstinence and reduced daily smoking without having an adverse effect on substance abuse rehabilitation when given at the same time as outpatient substance abuse treatment. Substance abuse treatment programs should not be hesitant to implement SC for patients seeking treatment for substance use disorders. Reference: Reid, M., et al. (2008). Smoking cessation treatment in community-based substance abuse rehabilitation programs. Journal of Substance Abuse Treatment 35(1): CTN-0010 Buprenorphine/Naloxone (Bup/Nx) Facilitated Rehabilitation for Heroin Addicted Adolescents/Young Adults. The usual treatment for opioid-addicted youth is detoxification and counseling. Some treatment providers are reluctant to use opioid agonist medications in this population, especially for long-term opioid maintenance. This study compared Bup/Nx treatment for 9 weeks and taper for 3 weeks to treatment as usual (Bup/Nx detox for 2 weeks). Both arms received counseling for 12 weeks. Primary Findings: Results of the study showed that continuing Bup/Nx for 12 weeks vs. 2 weeks improved outcomes. During weeks 1 through 12, patients in the 12-week Bup/Nx group reported less opioid use (P<.001), better retention (70% vs. 21%; p<.0001), less injecting (P=.01), and less use of cocaine (p<.001) and marijuana (p<.001). Continuing treatment with Bup/Nx for 12 weeks appeared to be safe in this population of opioid addicted adolescents and young adults. Dissemination: This CTN protocol was selected for development as a NIDA/SAMHSA Blending Team product. Reference: Woody, G., et al. (2008). Extended vs. short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial. Journal of the American Medical Association 300(17): CTN-0010-A-1 Cost-Effective Analysis (CEA) in the CTN: Bup/Nx Treatment for Opioid Addicted Youth. The goals of this project were to (1) perform a comprehensive economic analysis of Bup/Nx facilitated rehabilitation for opioid dependent adolescents/young adults by analyzing medical costs of treatment, cost-effectiveness, and cost-benefits (estimate the cost-effectiveness of the clinical intervention relative to the standard treatment in terms of cost per opioid free urine and in terms of cost per QALY and estimate net social benefits (Includes reduced crime, improved education and job outcomes, and improved HIV risk behavior); and (2) illustrate the methods for economic analysis of substance abuse interventions in a clinical trial and facilitate replication of these methods by other investigators in the CTN network. Primary Findings: Results varied somewhat by perspective. BUP cost providers approximately $1,514 more than DETOX per treatment episode in 2006 US dollars (p< 0.001), which translates into $25,049 per additional QALY (with no more than an 86% chance of being cost-effective at up to a $250,000 willingness-to-pay threshold) and $5,610 per additional opioid-free year (p < 0.001) assessed at year 1. For medical insurers, who benefitted from substantial savings on health care costs for those randomized to BUP, BUP cost $1,376/QALY

7 (with only an 86% chance of being cost-effective) and $308/opioid-free year (p<0.001). The point estimate of $31,264 per patient suggests that societal cost savings from BUP may be substantial, but the difference between groups was not significant at conventional levels in part due to the large variance estimated for crime costs which, although the largest savings component at $26,224, were a reflection of infrequently reported high-cost crimes. Reference: Polsky, D., et al. (2010). Cost-effectiveness of extended buprenorphine-naloxone treatment for opioid-dependent youth: data from a randomized trial. Addiction Jun 12 [Epub ahead of print]. CTN-0010-A-2 Comorbid Conditions in Adolescents with Opioid versus Alcohol and/or Marijuana Use Disorders. The purpose of this study was to determine if adolescents with opioid use disorder (OUD) have more co-morbidity than adolescents with marijuana and/or alcohol use disorders. In the study, we assessed substance use disorder diagnoses, psychiatric diagnoses, HIV-risk behaviors, and illegal acts. 94 adolescents (ages years) with a current OUD and 74 adolescents with a current non-oud cannabis/alcohol use disorders were recruited from admissions, predominantly residential, to Mountain Manor, a substance abuse treatment program in Baltimore, Maryland. Participants were assessed cross-sectionally using standardized interviews and self-report to determine group differences on demographic, substance use, psychiatric and HIV-risk behaviors. Primary Findings: The study confirmed that OUD adolescents evidenced greater impairment in academic, more substance use, more depressive symptoms, and higher IDU-related HIV-risk. Reference: Subramaniam, G., et al. (2009). Clinical characteristics of treatment-seeking adolescents with opioid versus cannabis/alcohol use disorders. Drug & Alcohol Dependence 99: CTN-0011 A Feasibility Study of a Telephone Enhancement Procedure (TELE) To Improve Participation in Continuing Care Activities. Relapse rates are frequently high during the first few months after substance abuse treatment, often reversing many of the positive results of treatment. Virtually all treatment programs strongly recommend that participants get involved in aftercare or continuing care activities after they are discharged. This study examined the feasibility and potential efficacy of phone calls to patients after discharge from short-term inpatient and residential substance abuse treatment programs to encourage compliance with continuing care plans. Primary Findings: While no difference was found between groups in self-reported attendance at one or more outpatient counseling sessions after discharge, participants receiving calls had a greater likelihood of documented attendance (48%) than those not called (37%); however, these results were not statistically significant. While the continuing care phone calls were feasible, the lack of clear evidence of efficacy suggests the need for further investigation of the role of telephone intervention to encourage compliance and improve long-term outcomes. Reference: Hubbard, R., et al. (2007). Telephone enhancement of long-term engagement (TELE) in continuing care for substance abuse treatment: A NIDA Clinical Trials Network (CTN) study. American Journal on Addictions 16(6): CTN-0012 Characteristics of Screening, Evaluation, and Treatment of HIV/AIDS, Hepatitis C Viral Infection, and Sexually Transmitted Infections in Substance Abuse Treatment Programs. Substance abuse is associated with a wide spectrum of medical disorders, including infections due to the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) as well as sexually transmitted infections. Despite the seriousness of this problem, there has not been a systematic investigation of infectious disease services in the substance abuse treatment

8 health care delivery system. This study surveyed CTP administrators and direct care providers, and reviews policies related to clinical guidelines and reimbursement through a survey of administrators of state substance abuse agencies or health departments. Primary Findings: Treatment programs varied in corporate structure, source of revenue, patient census, medical services, counseling services and staff education targeted HIV/AIDS more often than HCV or STI. The results of this study have already served as hypothesis generator for prospective HIV studies at the CTN. In addition to filling the information gap about available services for infectious disease in substance abuse treatment programs, this study provides a basis for future studies on the efficiency of these services and of health outcomes. Reference: Brown, L., et al. (2007). Health services for HIV/AIDS, HCV, and sexually transmitted infections in substance abuse treatment programs. Public Health Reports 122: CTN-0013 Motivational Enhancement Therapy to Improve Treatment Utilization and Outcome in Pregnant Substance Users. About 5% of women use illicit substances during pregnancy, and approximately 22% of these also report using tobacco or alcohol. While a number of treatment programs have begun to offer treatment specifically designed for pregnant substance abusers, it is difficult to keep these women in treatment. Brief motivational sessions have been found to improve treatment engagement and outcomes in both alcohol- and drug-using women. This study compared one such treatment intervention, Motivational Enhancement Therapy (MET), with standard treatment. The three individual MET sessions focused on developing rapport, exploring perceived pros and cons of using substances, reviewing the participant s feedback on the consequences of substance use and the status of her pregnancy, and developing a change plan or strengthening the commitment to change. Patients assigned to standard treatment received an equal number of visits consisting of the treatment normally given in that clinic. Primary Findings: Participants attended 62% of scheduled treatment on average, and reported decreased substance use during the first month of treatment, with no differences between MET and treatment-as-usual (TAU) participants. There was some evidence that the efficacy of MET varied between sites, and that MET might be more beneficial than TAU in decreasing substance use in minority participants. These results suggest that MET is not more effective than TAU for pregnant substance users in general, but that there might be particular subgroups or treatment programs for which MET might be more or less effective than TAU. Reference: Winhusen, T. et al. (2008). Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. Journal of Substance Abuse Treatment 35(2): CTN-0013-A-1 Trauma and Intravenous Drug Use among Pregnant Alcohol/Other Drug Abusing Women: Factors in Predicting Child Abuse Potential. This ancillary study has six circumscribed goals with pregnant substance abusing women: (a) to document the prevalence of exposure to traumatic life events; (b) to examine the prevalence of posttraumatic stress symptomatology; (c) to determine if trauma exposure and posttraumatic stress symptoms are related to treatment utilization and outcome; (d) to examine child abuse potential; (e) to determine if child abuse potential is related to trauma exposure and traumatic stress symptomatology; and (f) to determine if child abuse potential is related to treatment utilization and outcome. Primary Findings: In a sample of ethnically diverse substance using pregnant women, women with greater trauma symptomatology and women who were intravenous drug users reported significantly greater child abuse potential. The results suggest that because of the high levels of child abuse potential among this group, preventative interventions targeted toward child abuse potential are warranted for these women. Reference: Erickson, S. and Tonigan, J. (2008). Trauma and intravenous drug use among pregnant alcohol/other drug

9 abusing women: Factors in predicting child abuse potential. Alcoholism Treatment Quarterly 26(3): CTN-0014 Brief Strategic Family Therapy (BSFT) for Adolescent Drug Abusers. Adolescent drug abuse continues to be one of the most pressing public health issues in the United States our nation s teenagers continue to use illicit drugs at a worrisome rate. Broad reviews of the treatment outcome literature indicate that family interventions in general and BSFT in particular, are effective with drug-using youth. This study was designed to compare BSFT to treatment as usual (TAU). The researchers believe that BSFT will be much more effective than TAU in reducing adolescent drug use. They are also examining which of these treatment approaches does a better job of engaging adolescents and family members in treatment, decreasing problem behaviors, decreasing sexually risky behaviors, increasing pro-social activities (e.g., school, work), and improving the functioning of the family. Status: Study completed and manuscript accepted for publication in Journal of Consulting and Clinical Psychology. CTN-0014-A-1 Mediators and Moderators of BSFT for Adolescent Drug Use. Based on family systems theory, the investigators hypothesize that family functioning plays a critical mediating and moderating role in effective implementation of BSFT. Specifically, family change assessed during therapy should mediate effects of treatment (or BSFT intervention quality) on subsequent drug use outcomes, whereas family functioning assessed before therapy should moderate those effects, with BSFT proving most useful when prior family functioning is poor. This study also collected supplementary data on all therapists prior to their randomization (e.g., professional experience, recovery status, theoretical orientation), and on skill-acquisition trajectories of the BSFT therapists as they progress through training and the clinical trial. Status: Study completed and investigators are analyzing data for future publication. CTN-0015 Women s Treatment for Trauma and Substance Use Disorders. Post-Traumatic Stress Disorder (PTSD) is common among people with substance use disorders, and patients suffering from both of these conditions have a more difficult time meeting their treatment goals. Estimates suggest that as many00 as 80% of women seeking treatment for drug abuse report lifetime histories of sexual and/or physical assault. These facts highlight the importance of finding effective treatments for this high-risk population. Early studies showed that Seeking Safety, a treatment designed specifically for patients with PTSD and substance use disorders, held great potential for this population. This study compared the effectiveness of Seeking Safety added to substance abuse treatment-as-usual (TAU) with Women s Health Education added to TAU. The researchers looked at the effect of these treatment options on both substance use and the severity of PTSD symptoms. Primary Findings: Analyses showed large, clinically significant reductions in PTSD symptoms over the course of treatment and follow-up, but no reliable difference between the study groups. Substance use outcomes were not significantly different over time between the two treatments and at follow-up showed no significant change from baseline. Seeking Safety therapy was not associated with increases in substance use, adverse events, or dropout from treatment or study participation. The results reflect considerable opportunity to improve clinical outcomes in community-based treatments for these co-occurring conditions. Reference: Hien, D., et al. (2009). Multisite randomized trial of behavioral interventions for women with co-occurring PTSD and substance use disorders. Journal of Consulting & Clinical Psychology 77(4):

10 CTN-0015-A-1 Survey of Eating Disorder Symptoms among Women in Treatment for Substance Abuse Disorders. The primary goal of this study was to assess the prevalence of eating disorder symptoms, their relationship to other symptoms (e.g., SUD and PTSD symptoms), and their impact on treatment retention and outcome among adult female participants in two protocols CTN 0015 (Women and Trauma) and CTN 0019 (Safer Sex for Women). A brief screening instrument (The Eating Disorder Examination Questionnaire) was administered at baseline and post-treatment assessment periods. Primary Findings (0015): Two subgroups emerged; those reporting binge eating in the 28 days prior to baseline and those who reported no binge eating episodes. Women in the Binge group endorsed significantly higher ED, PTSD, and depression symptoms at baseline than those in the No Binge group. Although all participants showed significant reductions in PTSD symptoms and improvements in abstinence rates during the study period, the improvements for the Binge group were significantly lower. Reference: Cohen, L. R., Greenfield, S. F., Gordon, S., Killeen, T., Jiang, H., Zhang, Y., et al. (in press). Survey of eating disorder symptoms among women in treatment of substance abuse. American Journal of Addictions, 19(3). CTN-0016 Patient Feedback: A Performance Improvement Study in Outpatient Addiction Treatment. Although accrediting organizations, funding sources, and other agencies require community treatment providers to monitor performance, there are no studies showing that this is an effective practice or that it helps addiction treatment patients, clinicians, or managers. This feasibility study tested whether one such strategy, feeding back performance data to clinic staff, could improve patient attendance and abstinence. Ratings by patients of their group counseling experience, plus information on patient attendance and retention, were reported to clinicians and program managers twice a month. Every month managers and clinicians met to discuss the clinic-wide reports, identify opportunities for improvement, and make plans to improve the clinic-wide ratings. Primary Findings: The project demonstrated that the implementation of a semiautomatic performance improvement system directed at clinicians in addiction treatment facilities was generally feasible from both a research and a clinical perspective. The four participating clinics continued to use the system after the intervention phase, suggesting that implementation was sustainable. While the typical clinician accessed feedback reports only 2.3 times (out of a maximum of 8) over the course of the study, all clinicians participated in team meetings and were potential beneficiaries of suggestions for performance improvement and action steps that arose out of these meetings. In general, average alliance, treatment satisfaction, and drug/alcohol use outcomes were favorable across all assessments. Reference: Forman, R., et al. (2007). A feasibility study of a web-based performance improvement system for substance abuse treatment providers. Journal of Substance Abuse Treatment 33: CTN-0017 HIV and HCV Intervention in Drug Treatment Settings. Through June 2000, injection drug users accounted for more than a third of all cases of AIDS reported among persons aged 13 or older to the Centers for Disease Control and Prevention. Sixty percent of HCV transmission is related to injection drug use and as many as 50-95% of injection drug users are infected with HCV. This study tested two strategies to reduce the risk of contracting HIV or HCV by reducing risk behaviors in patients undergoing drug detoxification. The first included pre-test counseling, testing, post-test counseling, and the provision of HIV/HCV results. The second strategy, called therapeutic alliance, provided clients with information to guide them through the process of induction and aimed to facilitate transition to continuing care for drug treatment. Primary Findings: This study of 632 drug injectors enrolled in eight residential detoxification centers within the National Drug Abuse Treatment Clinical Trials Network tested three interventions to reduce drug and sex risk behaviors. Participants

11 were randomized to: (a) a two-session, HIV/HCV counseling and education (C&E) model added to treatment as usual (TAU), (b) a one-session, therapeutic alliance (TA) intervention conducted by outpatient counselors to facilitate treatment entry plus TAU, or (c) TAU. Significant reductions in drug and sex risk behaviors occurred for all three conditions over a 6-month follow-up period. C&E participants reported significantly greater rates of attending an HIV testing appointment, but this was not associated with better risk reduction outcomes. Reporting treatment participation within 2 months after detoxification and self-efficacy to practice safer injection behavior predicted reductions in injection risk behaviors. Findings indicate that participation in detoxification was followed by significant decreases in drug injection and risk behaviors for up to 6-months regardless of the treatment arm, as long as they were enrolled in detoxification programs; interventions added to standard treatment offered no improvement in risk behavior outcomes. Reference: Booth, R., et al. (2010). Reducing HIV-related Risk Behaviors among Injection Drug Users in Residential Detoxification. AIDS & Behavior Jul 21 [Epub ahead of print]. CTN-0018 Reducing HIV/STD Risk Behaviors: A Research Study for Men in Drug Abuse Treatment. Drug treatment itself can have a powerful positive effect on HIV drug use risk behavior, especially needle use behaviors. However, sexual risk behavior has received less attention and has been shown to be more difficult to change. Research suggests that skills-based HIV risk reduction interventions with peer group discussion and single sex sessions can reduce risky sexual behavior. This study evaluated a five-session HIV risk reduction group therapy designed specifically for men, Real Men Are Safe (REMAS). This therapy was compared to one session of HIV education, which is typically provided as standard care in drug treatment clinics. Primary Findings: The motivational and skills training HIV prevention program (REMAS) was associated with greater sexual risk reduction over a standard HIV education session, suggesting that substance abuse treatment programs can help reduce sexual risk among their patients by providing not only information but also practice skills. Reference: Calsyn, D., et al. (2009). Motivational and Skills Training HIV/STI Sexual Risk Reduction Groups for Men. Journal of Substance Abuse Treatment. 37: CTN-0019 Reducing HIV/STD Risk Behaviors: A Research Study for Women in Drug Abuse Treatment. Women in drug-using communities are one of the fastest growing groups of people with AIDS in the U.S. Female drug users, even if they are in drug treatment, are at especially high risk for heterosexual transmission of HIV: they are often in primary sexual relationships with male drug users, some continue to use drugs despite being in treatment, and, under the influence of drugs (especially cocaine or crack) they are more likely to engage in unprotected sex. It has been shown that drug abuse treatment can reduce activities related to drug use that increase the risk of HIV transmission. Sexual risk behaviors have received less attention, however, than those directly related to drug use. This study looked at a program for women in drug abuse treatment designed to build safer sexual skills and reduce unprotected sexual risk behavior. The program includes five sessions of group treatment that focus on assessing HIV risk, HIV safer sex problem solving, condom use, negotiation skills, and assertiveness training. This program was compared to one session of HIV education, which is typically provided as standard care in drug treatment clinics. Primary Findings: This protocol showed that a gender-specific, skills building intervention was effective and sustainable in reducing risk behavior in women in community drug treatment programs. Reference: Tross, S., et al. (2008). Effectiveness of HIV/STD sexual risk reduction groups for women in substance abuse treatment programs: Results of a NIDA Clinical Trials Network Trial. Journal of Acquired Immune Deficiency Syndromes 48(5):

12 CTN-0020 Job-Seekers Training for Patients with Drug Dependence. Drug abuse clients who are employed typically do better in their treatment than those who are unemployed. In addition, unemployment is a chronic problem in drug-dependent people. Despite the high rates of unemployment in this population, community treatment programs often do not have the resources to provide vocational services. This study examined the effectiveness of a 12-hour basic job-training program, modeled after the Job Seekers Workshop (JSW), designed to give patients the skills they need to find and secure a job and set vocational goals and methods for locating employment. Primary Findings: Participants in both the JSW and Standard Care (SC) conditions had similar results at 12- and 24-weeks for the primary outcome measure (i.e., obtaining a new taxed job or enrollment in a training program). Specifically, one-fifth of all participants at 12 weeks ( %) and nearly onethird at 24 weeks ( %) had positive outcomes, with obtaining a new taxed job accounting for the majority of cases. JSW group participants did not have higher rates of employment or training than SC controls. Rates of job acquisition were modest for both groups, suggesting more intensive interventions may be needed. Alternate targets (e.g., enhancing patient motivation, training in jobspecific skills) warrant further study as well. Reference: Svikis, DS et al. (2011). Randomized Multisite Trial of the Job Seekers' Workshop in Patients with Substance Use Disorders. Drug and Alcohol Dependence (in press) doi: /j.drugalcdep CTN-0020-A-1 Job Seekers' Training for Clients/Relatives with Drug Dependence (Specific to the Na'Nizhoozhi Center, Inc.). The study was a single site study, adapting the CTN 0020 protocol for a Native American site (Navajo) at the Na'Nizhoozhi Center, in New Mexico. In this study, 102 participants were randomized to either the Job Seekers Workshop, a three session, manualized program designed to train in the skills needed to find and secure a job; or a Job Interviewing Video intervention, a single session 40 minute video presentation designed to teach people the skills to find and secure a job. Primary Findings: No significant differences were found between the two groups for time to a new taxed job or enrollment in a job-training program. There were no significant differences between groups in substance use frequency at 3-month follow-up. Despite of the lack of a demonstrable treatment effect, this study established the feasibility of including a rural American Indian site in a rigorous CTN trial through a community-based participatory research approach. Reference: Foley, K, et al. (2010). Effect of Job Skills Training on Employment and Job Seeking Behaviors in an American Indian Substance Abuse Treatment Sample. Journal of Vocational Rehabilitation 33(3): [doi: /jvr ] CTN-0021 Motivational Enhancement Treatment to Improve Treatment Engagement and Outcome for Spanish-Speaking Individuals Seeking Treatment for Substance Abuse. This multisite randomized trial compared the effectiveness of three individual sessions of motivational enhancement therapy (MET) to three individual sessions of counseling as usual (CAU) on treatment retention and frequency of substance use, with all assessment and treatment sessions conducted in Spanish among 405 individuals seeking treatment for any type of current substance use. Primary Findings: 1) Both interventions resulted in reductions in substance use during the 4-week therapy phase, there were no significant treatment condition by time interactions nor site by treatment condition interactions; 2) Results suggest that the individual treatments delivered in Spanish were both attractive to and effective with this heterogeneous group of Hispanic adults, but the differential effectiveness of MET may be limited to those whose primary substance use problem is alcohol and may be fairly modest in magnitude. Reference: Carroll, K., et al. (2009). A multisite randomized

13 effectiveness trial of motivational enhancement therapy for Spanish-speaking substance users. Journal of Consulting and Clinical Psychology 77(5): CTN-0027 Starting Treatment with Agonist Replacement Therapies (START) Study. The CTN participates with the Division of Pharmacotherapies & Medical Consequences of Drug Abuse (DPMCDA) on a multi-centered trial to compare the effect of buprenorphine/naloxone (Bup/Nx) and methadone (MET) on liver function. This is a randomized, open-label, multi-center, Phase 4 study in participants entering opioid agonist treatment programs at community centers (methadone centers) throughout the country. The trial started in April Participants will be randomized until at least 300 evaluable participants are be available in both the Bup/Nx and MET study arms. The study randomized more than 1200 subjects and was implemented in 8 sites across 6 Nodes. Status: Study completed and Investigators are analyzing data. CTN-0027-A-1 START Pharmacogenetics: Exploratory Genetic Studies in Starting Treatment with Agonist Replacement Therapies. Patients participating in START will be offered the opportunity to volunteer for a genetics study that has the primary objective of genotyping patients for exploratory analyses. Genomic DNA from blood samples sent to the NIDA Genetics Repository will be extracted and saved for future study. Investigators at the University of Pennsylvania will study the frequency of gene variants that have primarily been associated with addiction, while the Medical University of South Carolina researchers will examine the relationship between treatment drug plasma concentrations and gene variants associated with drug disposition and transport. Status: Data collection completed and Investigators are analyzing data. CTN-0027-A-2 Retention of Suboxone Patients in START: Perspectives of Providers and Patients. The overall purposes of the supplemental study are (1) to identify barriers for retaining Suboxone patients in START, and (2) to address the barriers if study conditions and findings permit. Status: Study completed and Investigators are analyzing data. CTN-0028 Randomized Controlled Trial of Osmotic-Release Methylphenidate (OROS- MPH) for Attention Deficit Hyperactivity Disorder in Adolescents with Substance Use Disorders. The primary objectives of this study were to evaluate the efficacy of OROS-MPH (Concerta), relative to placebo, in treating attention deficit hyperactivity disorder (ADHD) and decreasing substance use in adolescents with ADHD and a substance use disorder (SUD). The study involved 303 participants, recruited from 11 community treatment sites. Primary Findings: OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD. However, OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures. Reference: Riggs, P., et al. (2011). Randomized controlled trial of osmoticrelease methylphenidate with cognitive-behavioral therapy in adolescents with attentiondeficit/hyperactivity disorder and substance use disorders. Journal of the American Academy of Child & Adolescent Psychiatry 50(9): CTN-0028-A-1 Does Methylphenidate Treatment for ADHD Increase the Rate of Smoking in Adolescents with Comorbid ADHD, SUD, and Nicotine Dependence? The purpose of this study was to measure any change in the rate of cigarette smoking among participants in the CTN-0028 trial. The hypothesis is that OROS-MPH treatment for ADHD

14 among adolescents with comorbid ADHD, SUD, and nicotine dependence will not increase the rate of cigarette smoking. Primary Findings: Baseline (pre-treatment) cigarette smoking was positively correlated with cannabis use. Negligible decline in cigarette smoking during treatment for non-nicotine SUD was observed in both medication groups. Regular cigarette and cannabis users at baseline who reduced their cannabis use by >50% also reduced cigarette smoking. Reference: Gray, K., et al. (2011). Cigarette and cannabis use trajectories among adolescents in treatment for attention-deficit/hyperactivity disorder and substance use disorders. Drug and Alcohol Dependence 117: CTN-0029 A Pilot Study of Osmotic-Release Methylphenidate (OROS-MPH) in Initiating and Maintaining Abstinence in Smokers with Attention Deficit Hyperactivity Disorder (ADHD). The primary objective of this study was to evaluate whether OROS-MPH (Concerta), relative to placebo, increases the effectiveness of standard smoking treatment (i.e., nicotine patch and individual smoking cessation counseling) in obtaining prolonged abstinence for smokers with ADHD. The study involved 255 participants, recruited from six sites. Primary Findings: Prolonged abstinence rates for the OROS-MPH and placebo groups did not differ significantly. OROS-MPH, relative to placebo, effectively treated ADHD and was safe and generally well tolerated. Reference: Winhusen, T., et al. (2010). Impact of attention-deficit/hyperactivity disorder (ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychiatry 71 (12): CTN-0030 Prescription Opioid Addiction Treatment Study (POATS). This was a randomized outpatient study for treatment-seeking participants dependent on prescription opioid analgesics. The primary objective was to determine whether the addition of individual drug counseling to the prescription of buprenorphine/naloxone (Bup/Nx) and Standard Medical Management (SMM) improves outcome. Participants were randomized at the beginning of each of two phases to receive BUP/NX paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual counseling). Six hundred and fifty three participants were randomized into Phase 1, and 360 participants were randomized into Phase 2. Status: Study completed and primary manuscript accepted for publication in Archives of General Psychiatry. CTN-0030-A-1 Collection of Economic Data for the Prescription Opioid Addiction Treatment Study. (Collaboration with NIDA DESPR) The aims of the study were: (1) to collect and validate facility data necessary to conduct economic analyses associated with comparisons of Bup/Nx treatment with SMM and EMM; and (2) to collect additional patient level data necessary to conduct economic analyses associated with comparisons of Bup/Nx treatment with SMM and EMM. Status: Study completed and Investigators are analyzing data. CTN-0030-A-2 Effects of Chronic Opioids on the Brain. (Collaboration with and support from NIDA DCNBR) The primary aim of this study is to obtain anatomical MR scans in subjects with a history of opioid use and to evaluate neural changes that may occur with such use by comparing these scans with age/gender healthy controls. Ten chronic opioid users were recruited to the study from the CTN-0030 participants at the McLean Hospital s addiction center and 10 age/gender matched healthy controls. Primary Findings: Prescription opioiddependent subjects had significantly decreased anisotropy in axonal pathways specific to amygdala as well as the internal and external capsules. Also, significant decreases in functional connectivity were found for seed regions that included the anterior insula, nucleus accumbens,