Objective Drug and alcohol abuse constitutes a major public health problem. Computer-delivered interventions have potential to improve access to quality care. The objective of this study was to evaluate the effectiveness of the Therapeutic Education System, an internet-delivered behavioral intervention that includes motivational incentives, as a clinician-extender in the treatment of substance use disorders. Method Adult men and women (N=507) entering 10 outpatient addiction treatment programs were randomly assigned to 12-weeks of treatment-as-usual (n=252) or treatment-as-usual + Therapeutic Education System, whereby the intervention substituted for 2 hours of standard care per week (n=255). Therapeutic Education System consists of 62 computer-interactive modules covering skills for achieving and maintaining abstinence, plus prize-based motivational incentives contingent on abstinence and treatment adherence. Treatment-as-usual consisted of individual and group counseling at the participating programs. Primary outcomes were (1) abstinence from drugs and heavy drinking measured by twice weekly urine drug screens and self-report, and (2) time to drop-out from treatment. Results Compared to treatment-as-usual, those receiving Therapeutic Education System reduced dropout from treatment (Hazard Ratio=0.72 [95% CI, 0.57-0.92], P=.010), and increased abstinence (Odds Ratio=1.62 [95% CI: 1.12-2.35], P=.010), an effect that was more pronounced among patients with a positive urine drug and/or breath alcohol screen at the point of study entry (n=228) (Odds Ratio=2.18 [95% CI: 1.30-3.68], P=.003). Conclusion Internet-delivered interventions, such as Therapeutic Education System, have the potential to expand access and improve addiction treatment outcomes; additional research is needed to assess effectiveness in non-specialty clinical systems and to differentiate the effect of Community Reinforcement Approach and Contingency Management.

Objective To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared to placebo for attention deficit hyperactivity disorder (ADHD) and impact on substance treatment outcomes in adolescents concurrently receiving cognitive behavioral therapy (CBT) for substance use disorders (SUD). Method 16-week randomized controlled multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13-18), meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcomes: (1) ADHD- clinician-administered ADHD Rating Scale (ADHD-RS), adolescent informant; (2) Substance- adolescent reported days of use in the past 28 days. Secondary outcome measures included parent ADHD-RS and weekly urine drug screens (UDS). Results There were no group differences on reduction in ADHD-RS scores (OROS-MPH: −19.2, 95% confidence interval [CI], −17.1 to −21.2; placebo,−21.2, 95% CI, −19.1 to −23.2) or reduction in days of substance use (OROS-MPH: −5.7 days, 95% CI, 4.0-7.4; placebo: −5.2 days, 95% CI, 3.5-7.0). Some secondary outcomes favored OROS-MPH including lower parent ADHD-RS scores at 8 (mean difference [md]=4.4, 95% CI, 0.8-7.9) and 16 weeks (md=6.9; 95% CI, 2.9-10.9) and more negative UDS in OROS-MPH (mean=3.8) compared to placebo (mean=2.8; P=0.04). Conclusions 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.

Pregnant substance users can benefit significantly from substance abuse treatment but treatment retention can be challenging. Two hundred pregnant substance users entering outpatient substance abuse treatment at 1 of 4 treatment programs were randomized to receive either 3 individual sessions of Motivational Enhancement Therapy for pregnant substance users (MET-PS) or the first 3 individual sessions normally provided by the program. All participants were encouraged to participate in all other treatment offered by the program. Outcome measures included treatment utilization according to clinic records, qualitative urine toxicology measures, and self-report of substance use. One hundred and sixty two participants (i.e., 81%) completed the 1 month active phase. Participants attended 62% of scheduled treatment on average and reported decreased substance use during the first month of treatment, with no differences between MET-PS and treatment as usual participants. There was some evidence that the efficacy of MET-PS varied between sites and that MET-PS might be more beneficial than TAU in decreasing substance use in minority participants. These results suggest that MET-PS is not more effective than treatment as usual for pregnant substance users in general but that there might be particular subgroups or treatment programs for which MET-PS might be more or less effective than treatment as usual.

In October 2002, the U.S. Food and Drug Administration approved buprenorphine-naloxone (Suboxone ® ) sublingual tablets as an opioid dependence treatment available for use outside traditionally licensed opioid treatment programs. The NIDA Center for Clinical Trials Network (CTN) sponsored two clinical trials assessing buprenorphine-naloxone for short-term opioid detoxification. These trials provided an unprecedented field test of its use in twelve diverse community-based treatment programs. Opioid-dependent men and women were randomized to a thirteen-day buprenorphine-naloxone taper regimen for short-term opioid detoxification. The 234 buprenorphine-naloxone patients averaged 37 years old and used mostly intravenous heroin. Direct and rapid induction onto buprenorphine-naloxone was safe and well tolerated. Most patients (83%) received 8 mg buprenorphine-2 mg naloxone on the first day and 90% successfully completed induction and reached a target dose of 16mg buprenorphine-4 mg naloxone in three days. Medication NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript compliance and treatment engagement was high. An average of 81% of available doses was ingested, and 68% of patients completed the detoxification. Most (80.3%) patients received some ancillary medications with an average of 2.3 withdrawal symptoms treated. The safety profile of buprenorphine-naloxone was excellent. Of eighteen serious adverse events reported, only one was possibly related to buprenorphine-naloxone. All providers successfully integrated buprenorphinenaloxone into their existing treatment milieus. Overall, data from the CTN field experience suggest that buprenorphine-naloxone is practical and safe for use in diverse community treatment settings, including those with minimal experience providing opioid-based pharmacotherapy and/or medical detoxification for opioid dependence.Opioid dependence and its associated disorders represent a serious public health problem in the United States and many other countries. Less than 20% of an estimated 898,000 U.S. heroin users 1 currently receive agonist treatment with methadone or LAAM. Further, sales and distribution of LAAM in the United States were discontinued in August 2003 as a result of severe cardiac-related adverse events associated with its use. Even fewer users receive antagonist treatment with naltrexone or some type of medical detoxification, followed by additional treatment such as that provided through a therapeutic community, short-term residential program, or drug-free outpatient program. Although each of these treatments can be effective, their availability and attractiveness to patients vary and are not sufficient to meet the current demand for treatment. The reasons are complex but include inadequate resources for patients to pay for current care, community resistance to new drug treatment programs (especially methadone), patient preference, and regulatory barriers that limit access to treatment.Buprenorphine hydrochloride (HCl), a derivative of the morp...

Objective High smoking rates in adults with attention deficit hyperactivity disorder (ADHD) and nicotine’s amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic release methylphenidate (OROS-MPH) to treat ADHD enhances response to smoking cessation treatment in smokers with ADHD. Method A randomized, double-blind, placebo-controlled, 11-week trial with a one month follow-up conducted at six clinical sites between December 2005 and January 2008. Adults (18–55), meeting DSM-IV criteria for ADHD and interested in quitting smoking were randomized to OROS-MPH titrated to 72 mg/day (n=127) or placebo (n=128). All participants received brief weekly individual smoking cessation counseling for 11 weeks and 21 mg/day nicotine patch starting on the smoking quit day (day 27) through study week 11. Outcome measures included prolonged smoking abstinence and DSM-IV ADHD Rating Scale (ADHD-RS) score. Results Of 255 randomized, 204 (80%) completed the trial. Prolonged abstinence rates, 43.3% and 42.2%, for the OROS-MPH and placebo groups, respectively, did not differ significantly (odds ratio, 1.1; 95% confidence interval, 0.63 – 1.79; p=0.81). OROS-MPH, relative to placebo, evidenced a greater reduction in DSM-IV ADHD-RS score (p<0.0001) and in cigarettes per day during the post-quit phase (p=.016). OROS-MPH, relative to placebo, increased blood pressure and heart rate to a statistically, but not clinically, significant degree; medication discontinuation did not differ significantly between treatments. Conclusions ADHD treatment did not improve smoking cessation success; OROS-MPH, relative to placebo, effectively treated ADHD and was safe and generally well tolerated in this healthy sample of adult ADHD smokers.

Objective To evaluate the impact of concurrent substance use disorder (SUD) and nicotine-dependence treatment for stimulant-dependent patients. Method A randomized, 10-week trial with follow-up at 3 and 6 months post-smoking quit date conducted at 12 SUD treatment programs between February 2010 and July 2012. Adults, meeting DSM-IV-TR criteria for cocaine and/or methamphetamine-dependence and interested in quitting smoking were randomized to treatment as usual (TAU; n=271) or TAU with smoking-cessation treatment (TAU+SCT, n=267). All participants received SUD TAU. TAU+SCT participants received weekly individual smoking cessation counseling and extended-release (XL) bupropion (300 mg/day) during weeks 1–10. During post-quit treatment (weeks 4–10), TAU+SCT participants received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. Results There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. TAU+SCT, relative to TAU, participants had significantly better outcomes for drug-free days at 6-month follow-up (X2(1)=4.09, p<.05), with a decrease in drug-free days from baseline of −1.3% in TAU+SCT and of −7.6% in TAU. TAU+SCT, relative to TAU, participants had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs. 2.2%; X2(1)=44.69, p<.001; OR=18.2). Conclusions These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient SUD treatment will not worsen, and may enhance, abstinence from non-nicotine substance use.

Computer-assisted interventions hold the promise of minimizing two problems that are ubiquitous in substance abuse treatment: the lack of ready access to treatment and the challenges to providing empirically-supported treatments. Reviews of research on computer-assisted treatments for mental health and substance abuse report promising findings, but study quality and methodological limitations remain an issue. In addition, relatively few computer-assisted treatments have been tested among illicit substance users. This manuscript describes the methodological considerations of a multi-site effectiveness trial conducted within the National Institute on Drug Abuse's (NIDA's) National Drug Abuse Treatment Clinical Trials Network (CTN). The study is evaluating a web-based version of the Community Reinforcement Approach, in addition to prize-based contingency management, among 500 participants enrolled in 10 outpatient substance abuse treatment programs. Several potential effectiveness trial designs were considered and the rationale for the choice of design in this study is described. The study uses a randomized controlled design (with independent treatment arm allocation), intention-to-treat primary outcome analysis, biological markers for the primary outcome of abstinence, long-term follow-up assessments, precise measurement of intervention dose, and a cost-effectiveness analysis. Input from community providers during protocol development highlighted potential concerns and helped to address issues of practicality and feasibility. Collaboration between providers and investigators supports the utility of infrastructures that enhance research partnerships to facilitate effectiveness trials and dissemination of promising, technologically innovative treatments. Outcomes from this study will further the empirical knowledge base on the effectiveness and cost-effectiveness of computer-assisted treatment in clinical treatment settings.

Few studies in community settings have evaluated predictors, mediators, and moderators of treatment success for medically supervised opioid withdrawal treatment. This report presents new findings about these factors from a study of 344 opioid dependent men and women prospectively randomized to either buprenorphine-naloxone or clonidine in an open-label 13-day medically-supervised withdrawal study. Subjects were either inpatient or outpatient in community treatment settings; however not randomized by treatment setting. Medication type (buprenorphine-naloxone versus clonidine) was the single best predictor of treatment retention and treatment success, regardless of treatment setting. Compared to the outpatient setting, the inpatient setting was associated with higher abstinence rates but similar retention rates when adjusting for medication type. Early opioid withdrawal severity mediated the relationship between medication type and treatment outcome with buprenorphine-naloxone being superior to clonidine at relieving early withdrawal symptoms. Inpatient subjects on clonidine with lower withdrawal scores at baseline did better than those with higher withdrawal scores; inpatient subjects receiving buprenorphine-naloxone did better with higher withdrawal scores at baseline than those with lower withdrawal scores. No relationship was found between treatment outcome and age, gender, race, education, employment, marital status, legal problems, baseline depression, or length/severity of drug use. Tobacco use was associated with worse opioid treatment outcomes. Severe baseline anxiety symptoms doubled treatment success. Medication type (buprenorphine-naloxone) was the most important predictor of positive outcome; however the paper also considers other clinical and policy implications of other results, including that inpatient setting predicted better outcomes and moderated medication outcomes.