Faculty Bibliography

OBJECTIVE: The purpose of this study was to explore changes in transaminase values associated with buprenorphine treatment and hepatitis C status among opioid dependent subjects aged 15-21. METHODS: 152 subjects seeking treatment for opioid dependence were randomized to 2-week detoxification with buprenorphine/naloxone (DETOX) or 12 weeks buprenorphine/naloxone (BUP). Liver chemistries including transaminases were obtained baseline and at 4, 8, and 12 weeks. 111 patients had at least one set of transaminases during treatment and were included in analyses of treatment effects. RESULTS: Overall, 8/60 BUP participants vs. 12/51 DETOX participants had at least one elevated ALT value during follow-up (Chi-square n.s.). 5/60 BUP participants vs. 11/51 DETOX participants had at least one elevated AST value (Chi-square = 3.194, p = .048). Twenty-eight out of 152 participants were hepatitis C (HCV) positive at baseline, and 4 seroconverted within 12 weeks, 2 in each group. HCV status was significantly associated with transaminase abnormalities (p = .009 and p = .006 for ALT an AST, respectively). HCV status had a strong effect on transaminase abnormalities among participants assigned to DETOX, but not among those assigned to BUP. CONCLUSIONS: No evidence was found for hepatotoxicity of buprenorphine in this exploratory analysis. HCV was present in a significant minority of participants and was a significant predictor of transaminase elevation. Results suggest that stabilization on buprenorphine may decrease the frequency of transaminase abnormalities associated with HCV in opioid dependent young people. The high rate of seroconversion underscores the importance of effective treatment and prevention.

Employment difficulties are common among American Indian individuals in substance abuse treatment. To address this problem, the Southwest Node of NIDA's Clinical Trials Network conducted a single-site adaptation of its national Job Seekers Workshop study in an American Indian treatment program, Na'Nizhoozhi Center (NCI). 102 (80% men, 100% American Indian) participants who were in residential treatment and currently unemployed were randomized to (1) a three session, manualized program (Job seekers workshop: JSW) or (2) a 40-minute Job Interviewing Video: JIV). Outcomes were assessed at 3-month follow up: 1) number of days to a new taxed job or enrollment in a job-training program, and 2) total hours working or enrolled in a job-training program. 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. These results do not support the use of the costly and time-consuming JSW intervention in this population and setting. 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.

Findings from neuroscience research hold promise for improved treatments for and prevention of substance use disorders (SUD), but ethical concerns about psychopharmacological research involving SUD may potentially undermine scientific progress. This article reviews the literature pertaining to seven ethical requirements that elucidate a coherent framework for evaluating the ethics of clinical SUD research protocols. Those requirements are social or scientific value, scientific validity, fair subject selection, favorable risk-benefit ratio, independent review, informed consent, and respect for potential or enrolled subjects. An evidence-based analysis suggests that sound pharmacological research in SUD can safeguard the welfare of research participants while collecting valuable scientific data and benefiting society.

The coming decades will see exciting breakthroughs in the treatment of SUDs, such as further elucidation of the genetic mechanisms of addiction. Yet if the past is any guide to the future, each new discovery will bring with it new challenges to the core ethical obligations of honoring informed consent, protecting confidentiality, and respecting justice, while also protecting the public from harm and ensuring the good of the individual patient. For the emerging scientific shift to a biobehavioral model of addiction to transform cultural attitudes and enhance treatment and research will require the scientifically rigorous and ethically sound agency of ethicists and addiction professionals to influence public policy. The growing body of neurobiologic evidence that contests traditional assumptions about free will and responsibility will evoke more deliberate and nuanced approaches to informed consent and treatment participation and dispute the forensic orientation in drug policy. If this unprecedented paradigm change can influence health care decision making in a reasoned and balanced fashion, there is real hope that the cultural stigma, which has warranted highly stringent confidentiality protections, and the disenfranchisement underlying health disparities in addiction treatment may move in the direction of compassionate and competent care for all those who suffer from addiction.

BACKGROUND: This study investigated whether subgroups of alcohol-dependent patients responded differently to naltrexone versus placebo in the NIAAA COMBINE study. In particular, the A versus B and the Early Onset versus Late Onset typologies were examined. Relative to Type A alcoholics, Type B alcoholics are characterized by greater severity, earlier onset, stronger family history, more childhood risk factors (e.g., conduct disorder), and greater frequency of comorbid psychiatric and substance use disorders. METHODS: COMBINE study participants were categorized as Type A or Type B using k-means cluster analysis and variables from 5 domains that have been shown to replicate the original Babor typology efficiently. Early Onset was defined as alcohol dependence beginning before age 25. For the planned analyses, the sample was reduced to the 618 participants receiving naltrexone alone or placebo, either with medical management (MM) alone or with MM plus the Combined Behavioral Intervention (CBI). The a priori primary outcome was percent heavy drinking days during treatment in the groups receiving MM without CBI. RESULTS: Among those receiving MM without CBI, Type A alcoholics had better drinking outcomes with naltrexone than placebo, whereas medication condition did not influence outcomes significantly in the Type Bs. Age of onset was not significantly related to outcome. For those receiving CBI, no significant effects were found for either typology. CONCLUSIONS: In this sample, the beneficial effects of opioid antagonism were limited to Type A alcoholics receiving treatment in a MM model. Future studies should investigate the relationship between clinically relevant genotypes, phenotypes such as typologies, and treatment response. More work is also needed to develop practical algorithms for phenotypic assignment.