Faculty Bibliography

OBJECTIVE:To estimate how results would have varied if a substance abuse clinical trial had been conducted with nationally representative adults with substance use and with representative adults receiving substance use treatment. METHODS:Results were analyzed from a multisite clinical trial comparing the effectiveness of the Therapeutic Education System to treatment as usual for outpatient addiction treatment (n = 507). Patients were recruited between June 2010 and August 2011. Abstinence was the primary outcome. The general population sample and general population-treated samples were derived from Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (n = 43,093). Propensity scores provided a standardized measure of the difference between clinical trial participants and the 2 NESARC samples. The clinical trial was reanalyzed by reweighting the sample with propensity scores derived from the 2 samples to obtain generalizable estimates of treatment effects. RESULTS:Before the clinical trial sample was reweighted, the odds ratio (OR) of response to Therapeutic Education System versus treatment as usual in the trial was 1.62 (95% CI, 1.12-2.35). After the sample was reweighted to be representative of the 2 NESARC groups, ORs were 1.33 (95% CI, 0.34-5.26) for the representative sample with any substance use and 1.64 (95% CI, 0.82-3.27) for the representative treated sample. CONCLUSIONS:Applying propensity score weighting to clinical trial results provides a method for estimating the population generalizability of clinical trial findings that relies on effect moderators observed in the study sample and population. Broader confidence intervals in the reweighted samples do not necessarily indicate lack of efficacy of the Therapeutic Education System but rather greater uncertainty concerning effectiveness in general population samples.

BACKGROUND:Sexual risk behavior is now the primary vector of HIV transmission among substance users in the United States with gender as a crucial moderator of risk behavior. OBJECTIVES:The purpose of this study was to examine gender differences in factors (age, race/ethnicity, education) that predict main-partner unprotected sexual occasions (USO) using the unique platform of two parallel NIDA National Drug Abuse Treatment Clinical Trials Network gender-specific safer sex intervention trials. METHODS:Baseline assessments of male (N = 430) and female (N = 377) participants included demographic characteristics; past 3-month sexual activity; and a diagnostic assessment for alcohol, cocaine/stimulant, and opioid use disorders. Using mixed effects generalized linear modeling of the main outcome USO, two-way interactions of gender with age, race/ethnicity, and education were evaluated and adjusted by alcohol, cocaine/stimulant, or opioid use disorder. RESULTS:When adjusted for alcohol use disorder, the interaction of education and gender was significant. For men, a high school or greater education was significantly associated with more USO compared to men with less than high school. For women, greater than high school education was significantly associated with less USO compared to women with a high school education. None of the other interactions were significant when adjusted for cocaine/stimulant or opioid use disorder. Conclusions/Importance: This study demonstrates gender differences in the relationship of education, alcohol use disorder, and main-partner USO in individuals in substance abuse treatment. This underscores the importance of considering demographic and substance use factors in HIV sexual risk behavior and in crafting prevention messages for this population.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Extended-release naltrexone (XR-NTX) is FDA-approved to prevent relapse in patients with Opioid Use Disorder. However little is known about long-term use among community-based outpatients. METHODS:Retrospective chart review and long-term follow-up survey among individuals (N = 168) who entered an outpatient XR-NTX trial between 2011 and 2015, during which participants were offered three monthly injections of XR-NTX at no cost. The survey consisted of 35 questions covering a total of four domains: (1) substance use; (2) treatment continuation; (3) barriers; and (4) attitudes. RESULTS:Fifty-seven respondents were successfully surveyed, including 50% of those initially receiving all three XR-NTX injections ("study completers") in the parent study. Study completion was associated with superior outcomes and less likely relapse (defined as daily use), with a much greater time to relapse despite higher rates of concurrent non-opioid substance use. However the majority of participants discontinued treatment with XR-NTX at study completion, largely due to attitudes of "feeling cured" and "wanting to do it on my own" rather than external barriers such as cost or side effects. CONCLUSION/CONCLUSIONS:Patients who initiate treatment with XR-NTX might benefit from anticipatory guidance and motivational techniques to encourage long-term adherence as many will experience internal barriers to continuation. Our findings are reassuring that few patients experience side effects or adverse events complicating the effectiveness or safety of long-term use of XR-NTX. SCIENTIFIC SIGNIFICANCE/CONCLUSIONS:Among outpatients who successfully receive 3 monthly XR-NTX injections, many will prematurely discontinue treatment due to internal attitudes, such as "feeling cured." (Am J Addict 2017;26:319-325).

OBJECTIVE:At present there is no established optimal approach for transitioning opioid-dependent adults to extended-release injection naltrexone (XR-naltrexone) while preventing relapse. The authors conducted a trial examining the efficacy of two methods of outpatient opioid detoxification for induction to XR-naltrexone. METHOD:Participants were 150 opioid-dependent adults randomly assigned 2:1 to one of two outpatient detoxification regimens, naltrexone-assisted detoxification or buprenorphine-assisted detoxification, followed by an injection of XR-naltrexone. Naltrexone-assisted detoxification lasted 7 days and included a single day of buprenorphine followed by ascending doses of oral naltrexone along with clonidine and other adjunctive medications. Buprenorphine-assisted detoxification included a 7-day buprenorphine taper followed by a week-long delay before administration of XR-naltrexone, consistent with official prescribing information for XR-naltrexone. Participants from both groups received behavioral therapy focused on medication adherence and a second dose of XR-naltrexone. RESULTS:Compared with participants in the buprenorphine-assisted detoxification condition, participants assigned to naltrexone-assisted detoxification were significantly more likely to be successfully inducted to XR-naltrexone (56.1% compared with 32.7%) and to receive the second injection at week 5 (50.0% compared with 26.9%). Both models adjusted for primary type of opioid use, route of opioid administration, and morphine equivalents at baseline. CONCLUSIONS:These results demonstrate the safety, efficacy, and tolerability of low-dose naltrexone, in conjunction with single-day buprenorphine dosing and adjunctive nonopioid medications, for initiating adults with opioid dependence to XR-naltrexone. This strategy offers a promising alternative to the high rates of attrition and relapse currently observed with agonist tapers in both inpatient and outpatient settings.

BACKGROUND AND AIMS: Criminal justice-involved individuals are highly susceptible to opioid relapse and overdose-related deaths. In a recent randomized trial, we demonstrated the effectiveness of extended-release naltrexone (XR-NTX; Vivitrol(R) ) in preventing opioid relapse among criminal justice-involved US adults with a history of opioid use disorder. The cost of XR-NTX may be a significant barrier to adoption. Thus, it is important to account for improved quality of life and downstream cost-offsets. Our aims were to (1) estimate the incremental cost per quality-adjusted life-year (QALY) gained for XR-NTX versus treatment as usual (TAU) and evaluate it relative to generally accepted value thresholds; and (2) estimate the incremental cost per additional year of opioid abstinence. DESIGN: Economic evaluation of the aforementioned trial from the taxpayer perspective. Participants were randomized to 25 weeks of XR-NTX injections or TAU; follow-up occurred at 52 and 78 weeks. SETTING: Five study sites in the US Northeast corridor. PARTICIPANTS: A total of 308 participants were randomized to XR-NTX (n = 153) or TAU (n = 155). MEASUREMENTS: Incremental costs relative to incremental economic and clinical effectiveness measures, QALYs and abstinent years, respectively. FINDINGS: The 25-week cost per QALY and abstinent-year figures were $162 150 and $46 329, respectively. The 78-week figures were $76 400/QALY and $16 371/abstinent year. At 25 weeks, we can be 10% certain that XR-NTX is cost-effective at a value threshold of $100 000/QALY and 62% certain at $200 000/QALY. At 78 weeks, the cost-effectiveness probabilities are 59% at $100 000/QALY and 76% at $200 000/QALY. We can be 95% confident that the intervention would be considered 'good value' at $90 000/abstinent year at 25 weeks and $500/abstinent year at 78 weeks. CONCLUSIONS: While extended-release naltrexone appears to be effective in increasing both quality-adjusted life-years (QALYs) and abstinence, it does not appear to be cost-effective using generally accepted value thresholds for QALYs, due to the high price of the injection.

BACKGROUND: The acceptability, feasibility and effectiveness of web-based interventions among criminal justice involved populations are understudied. This study is a secondary analysis of baseline characteristics associated with criminal justice system (CJS) status as treatment outcome moderators among participants enrolling in a large randomized trial of a web-based psychosocial intervention (Therapeutic Education System [TES]) as part of outpatient addiction treatment. METHODS: We compared demographic and clinical characteristics, TES participation rates, and the trial's two co-primary outcomes, end of treatment abstinence and treatment retention, by self-reported CJS status at baseline: 1) CJS-mandated to community treatment (CJS-mandated), 2) CJS-recommended to treatment (CJS-recommended), 3) no CJS treatment mandate (CJS-none). RESULTS: CJS-mandated (n = 107) and CJS-recommended (n = 69) participants differed from CJS-none (n = 331) at baseline: CJS-mandated were significantly more likely to be male, uninsured, report cannabis as the primary drug problem, report fewer days of drug use at baseline, screen negative for depression, and score lower for psychological distress and higher on physical health status; CJS-recommended were younger, more likely single, less likely to report no regular Internet use, and to report cannabis as the primary drug problem. Both CJS-involved (CJS -recommended and -mandated) groups were more likely to have been recently incarcerated. Among participants randomized to the TES arm, module completion was similar across the CJS subgroups. A three-way interaction of treatment, baseline abstinence and CJS status showed no associations with the study's primary abstinence outcome. CONCLUSIONS: Overall, CJS-involved participants in this study tended to be young, male, and in treatment for a primary cannabis problem. The feasibility and effectiveness of the web-based psychosocial intervention, TES, did not vary by CJS-mandated or CJS-recommended participants compared to CJS-none. Web-based counseling interventions may be effective interventions as US public safety policies begin to emphasize supervised community drug treatment over incarceration.

In addition to difficulties in daily social functioning, regular cocaine users have decrements in social processing (the cognitive and affective processes underlying social behavior) relative to non-users. Little is known, however, about the effects of clinically-relevant pharmacological agents, such as cocaine and potential treatment medications, on social processing in cocaine users. Such drug effects could potentially alleviate or compound baseline social processing decrements in cocaine abusers. Here, we assessed the individual and combined effects of smoked cocaine and a potential treatment medication, levodopa-carbidopa-entacapone (LCE), on facial emotion recognition in cocaine smokers. Healthy non-treatment-seeking cocaine smokers (N = 14; two female) completed this 11-day inpatient within-subjects study. Participants received LCE (titrated to 400mg/100mg/200mg b.i.d.) for five days with the remaining time on placebo. The order of medication administration was counterbalanced. Facial emotion recognition was measured twice during target LCE dosing and twice on placebo: once without cocaine and once after repeated cocaine doses. LCE increased the response threshold for identification of facial fear, biasing responses away from fear identification. Cocaine had no effect on facial emotion recognition. Results highlight the possibility for candidate pharmacotherapies to have unintended impacts on social processing in cocaine users, potentially exacerbating already existing difficulties in this population.

BACKGROUND:Substance misuse and excessive alcohol consumption are major public health issues. Internet-based interventions for substance use disorders (SUDs) are a relatively new method for addressing barriers to access and supplementing existing care. This study examines cost-effectiveness in a multisite, randomized trial of an internet-based version of the community reinforcement approach (CRA) with contingency management (CM) known as the Therapeutic Education System (TES). METHODS:Economic evaluation of the 12-week trial with follow-up at 24 and 36 weeks. 507 individuals who were seeking therapy for alcohol or other substance use disorders at 10 outpatient community-based treatment programs were recruited and randomized to either treatment as usual (TAU) or TES+TAU. Sub-analyses were completed on participants with a poorer prognosis (i.e., those not abstinent at study entry). RESULTS:From the provider's perspective, TES+TAU as it was implemented in this study costs $278 (SE=87) more than TAU alone after 12 weeks. The quality-adjusted life years gained by TES+TAU and TAU were similar; however, TES+TAU has at least a 95% chance of being considered cost-effective for providers and payers with willingness-to-pay thresholds as low as $20,000 per abstinent year. Findings for the subgroup not abstinent at study entry are slightly more favorable. CONCLUSIONS:With regard to the clinical outcome of abstinence, our cost-effectiveness findings of TES+TAU compare favorably to those found elsewhere in the CM literature. The analyses performed here serve as an initial economic framework for future studies integrating technology into SUD therapy.

The psycholinguistic analysis of client-counselor interactions indicates that how individuals talk about their substance use is associated with treatment outcome. However, the processes by which client speech influences out-of-session behaviors have not been clearly delineated. This study investigated the relationships between deriving relations-a key behavioral process by which language and cognition may come to influence behavior, shifts in the strength of client talk in favor of change, and treatment outcome among 75 cocaine-dependent participants (23% Female). Participants were trained to relate cocaine words, nonsense syllables, and negative-consequence words and were then assessed for a derived relation of equivalence before starting treatment. The DARN-C coding system was used to quantify the strength of participant speech during an early cognitive behavior therapy counseling session. Cocaine use during treatment was the outcome of interest. The analyses (a) characterized the process of deriving relations among individuals seeking help for their misuse of cocaine, (b) tested the relationships between shifts in the strength of participants' speech in favor of change and treatment outcome, and (c) tested if deriving equivalence relations moderated the relationship between shifts in the strength of in-session speech and treatment response. Results indicated that a minority of participants derived equivalence relations, however increases in the strength of commitment language predicted less cocaine use during treatment only among those who did. The findings suggest deriving relations may be an important process by which changes in the strength of commitment language comes to influence substance use.

BACKGROUND:Benzodiazepine use disorders are a common clinical problem among methadone maintenance treatment patients and have adverse effects on clinical outcomes. OBJECTIVES:To evaluate gabapentin for the outpatient treatment of benzodiazepine abuse or dependence in methadone maintenance patients. METHODS:Participants (n = 19) using benzodiazepines at least 4 days per week were enrolled into an 8-week randomized double-blind placebo-controlled outpatient pilot trial. All participants received a manual-guided supportive psychotherapy aimed to promote abstinence. Study medication was titrated over a 2-week period to a maximum dose of gabapentin 1200 mg or placebo three times a day. Benzodiazepine use was assessed using urine toxicology confirmed self-report. Benzodiazepines were not provided as part of study participation; participants were provided guidance to gradually reduce benzodiazepine intake. RESULTS:Sixteen participants had post-randomization data for analysis. Retention at week eight was 50%. The mean dose of gabapentin achieved by titration was 2666 mg/day (SD = ± 1446). There were no significant between group differences on benzodiazepine use outcomes (amount benzodiazepine per day [Mann-Whitney U = 27, p = 0.745], abstinent days per week [U = 28, p = 0.811]) and Clinical Instrument Withdrawal Assessment (CIWA)-benzodiazepines scale (U = 29.0, p = 0.913). One participant in the gabapentin group discontinued study medication because of peripheral edema. Two participants in the placebo group requested admission for inpatient detoxification treatment. CONCLUSION:In outpatient methadone-maintained patients with benzodiazepine use disorder, gabapentin did significantly decrease benzodiazepine use relative to placebo. The small sample recruited for this trial may have limited the ability to detect a group difference.