Access to treatment for opioid use disorders: Medical student preparation.

The current opioid epidemic requires new approaches to increasing access to treatment for patients with opioid use disorders and to improve availability of medication assisted treatment. We propose a model where medical students complete the necessary training to be eligible for the waiver to prescribe opioid medications to treat these disorders by the time of medical school graduation. This plan would increase the number of Drug Abuse Treatment Act of 2000 (DATA 2000) waivered physicians who could gain additional experience in treating substance use disorders during residency and provide the access to clinical care needed for individuals suffering with opioid use disorder. (Am J Addict 2017;26:316-318).

A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy.

BACKGROUND: Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4(+) T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4(+) T cells at concentrations achieved in vivo. METHODS: We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1-infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4(+) T cells. RESULTS: Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). CONCLUSIONS: Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug.

The Affordable Care Act: implementation and implications for addiction specialty care.

Converging in 2015 are the implementation of key pieces of the Affordable Care Act (ACA) and the implementation of the International Classification of Diseases, 10th edition (ICD-10). The implications for addiction care in the United States are substantial. This editorial discusses opportunities and challenges presented by these major changes to medicine and addiction specialty care.

Effects of HCV seropositive status on buprenorphine pharmacokinetics in opioid-dependent individuals.

BACKGROUND AND OBJECTIVES: The purpose of this study was to examine the effect of hepatitis C virus (HCV) infection on buprenorphine pharmacokinetics in opioid-dependent, buprenorphine/naloxone-maintained adults. METHODS: A retrospective analysis of buprenorphine pharmacokinetics in HCV seropositive and seronegative buprenorphine/naloxone-maintained individuals (N = 49) was undertaken. RESULTS: Relative to HCV seronegative subjects, HCV seropositive subjects had higher buprenorphine exposure, as demonstrated by elevated buprenorphine AUC and Cmax values (p = .03 and .02, respectively) and corresponding elevations in the metabolites, buprenorphine-3-glucuronide AUC values (p = .03) and norbuprenorphine-3-glucuronide AUC and C24 values (p = .05 and .03, respectively). DISCUSSION AND CONCLUSIONS: HCV infection was associated with higher plasma concentrations of buprenorphine and buprenorphine metabolites. SCIENTIFIC SIGNIFICANCE AND FUTURE DIRECTIONS: Findings suggest the potential for opioid toxicity among HCV-infected patients treated with buprenorphine/naloxone, and possible hepatotoxic effects related to increased buprenorphine exposure. HCV-infected patients receiving buprenorphine may need lower doses to maintain therapeutic plasma concentrations.

Interaction of disulfiram with antiretroviral medications: efavirenz increases while atazanavir decreases disulfiram effect on enzymes of alcohol metabolism.

BACKGROUND AND OBJECTIVES: Alcohol abuse complicates treatment of HIV disease and is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders possibly related to concerns about drug interactions between antiretroviral (ARV) medications and DIS. METHOD: This pharmacokinetics study (n=40) examined the effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase (ALDH) activity which mediates the DIS-alcohol reaction. RESULTS: EFV administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate (DIS carbamate), a metabolite of DIS (p=.001) and a precursor to the metabolite responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO). EFV was associated with increased DIS inhibition of ALDH activity relative to DIS alone administration possibly as a result of EFV-associated induction of CYP 3A4 which metabolizes the carbamate to DETC-MeSO (which inhibits ALDH). Conversely, ATV co-administration reduced the effect of DIS on ALDH activity possibly as a result of ATV inhibition of CYP 3A4. DIS administration had no significant effect on any ARV studied. DISCUSSION/CONCLUSIONS: ATV may render DIS ineffective in treatment of alcoholism. FUTURE DIRECTIONS: DIS is infrequently utilized in HIV-infected individuals due to concerns about adverse interactions and side effects. Findings from this study indicate that, with ongoing clinical monitoring, DIS should be reconsidered given its potential efficacy for alcohol and potentially, cocaine use disorders, that may occur in this population.

A primary care approach to substance misuse.

Substance misuse is common among patients in primary care settings. Although it has a substantial health impact, physicians report low levels of preparedness to identify and assist patients with substance use disorders. An effective approach to office-based treatment includes a coherent framework for identifying and managing substance use disorders and specific strategies to promote behavior change. Brief validated screening tools allow rapid and efficient identification of problematic drug use, including prescription medication misuse. After a positive screening, a brief assessment should be performed to stratify patients into three categories: hazardous use, substance abuse, or substance dependence. Patients with hazardous use benefit from brief counseling by a physician. For patients with substance abuse, brief counseling is also indicated, with the addition of more intensive ongoing follow-up and reevaluation. In patients with substance dependence, best practices include a combination of counseling, referral to specialty treatment, and pharmacotherapy (e.g., drug tapering, naltrexone, buprenorphine, methadone). Comorbid mental illness and intimate partner violence are common in patients with substance use disorders. The use of a motivational rather than a confrontational communication style during screening, counseling, and treatment is important to improve patient outcomes.

Team-based learning exercise efficiently teaches brief intervention skills to medicine residents.

BACKGROUND: Evaluations of substance use screening and brief intervention (SBI) curricula typically focus on learner attitudes and knowledge, although effects on clinical skills are of greater interest and utility. Moreover, these curricula often require large amounts of training time and teaching resources. This study examined whether a 3-hour SBI curriculum for internal medicine residents utilizing a team-based learning (TBL) format is effective for SBI skills as measured by a standardized patient (SP) assessment. METHODS: A waitlist-controlled design was employed. RESULTS: Twenty-four postgraduate year 2 (PGY-2) and PGY-3 residents participated in a SP assessment prior to the TBL session (waitlist control group) and 32 participated in a SP assessment after the TBL session (intervention group). The intervention residents demonstrated better brief intervention skills than waitlist control residents, but there were no differences between the groups in screening and assessment skills. Residents receiving the TBL curriculum prior to the SP assessment reported increased confidence in all SBI skills. CONCLUSION: Findings indicate that a brief educational intervention can improve brief intervention skills. However, more intensive education may be needed to improve substance use screening and assessment.

Interactions between buprenorphine and the protease inhibitors darunavir-ritonavir and fosamprenavir-ritonavir.

BACKGROUND: This study examined drug interactions between buprenorphine, a partial opioid agonist used for opioid dependence treatment and pain management, and the protease inhibitors (PIs) darunavir-ritonavir and fosamprenavir-ritonavir. METHODS: The pharmacokinetics of buprenorphine and its metabolites and symptoms of opioid withdrawal or excess were compared in opioid-dependent, buprenorphine-naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (11 for darunavir-ritonavir and 10 for fosamprenavir-ritonavir) before and after 15 days of PI administration. PI pharmacokinetics and adverse effects were compared between the buprenorphine-maintained participants and an equal number of sex-, age-, race-, and weight-matched, healthy, non-opioid-dependent volunteers who received darunavir-ritonavir or fosamprenavir-ritonavir but not buprenorphine. RESULTS: There were no significant changes in buprenorphine or PI plasma levels and no significant changes in medication adverse effects or opioid withdrawal. Increased concentrations of the inactive metabolite buprenorphine-3-glucuronide suggested that darunavir-ritonavir and fosamprenavir-ritonavir induced glucuronidation of buprenorphine. CONCLUSIONS: Dose adjustments are not likely to be necessary when buprenorphine and darunavir-ritonavir or fosamprenavir-ritonavir are coadministered for the treatment of opioid dependence and HIV disease.

Course and treatment of buprenorphine/naloxone withdrawal: an analysis of case reports.

Currently published information on buprenorphine-naloxone withdrawal recommends a gradually decreasing dosage over weeks to months. In this case report, abrupt cessation of buprenorphine/naloxone at various doses, and after variable durations of treatment, resulted in mild opiate withdrawal lasting over approximately 1-2 days that did not require additional opioid medication or only specific symptom-relieving, non-opioid, medications. Lengthy withdrawal regimens might prolong withdrawal symptoms unnecessarily, perhaps increasing the risk of re-addiction. Controlled studies of buprenorphine/naloxone withdrawal regimens over varying time frames would help to illuminate the most effective means of opioid discontinuation and inform clinical care.

Using needs assessment to develop curricula for screening, brief intervention, and referral to treatment (SBIRT) in academic and community health settings.

This article describes the use of a brief needs assessment survey in the development of alcohol and drug screening, brief intervention, and referral to treatment (SBIRT) curricula in 2 health care settings in the San Francisco Bay Area. The samples included university medical center faculty (n = 27) and nonphysician community health and social service providers in a nearby suburban county (n = 21). Informed by curriculum development theory and motivational interviewing strategies, questions regarding clinical and educational priorities, perceived importance and confidence with screening and intervention techniques, and referral resource availability were included. Medical center faculty expressed greater concern about limited appointment time (P = .003), adequacy of training (P = .025), and provider confidence (P = .038) as implementation obstacles and had lower confidence in delivering SBIRT (P = .046) and providing treatment referrals (P = .054) than community providers. The authors describe their approach to integrating needs assessment results into subsequent curriculum development. Findings highlight potential differences between physician and nonphysician training needs.

Using standardized patients to evaluate screening, brief intervention, and referral to treatment (SBIRT) knowledge and skill acquisition for internal medicine residents.

Comprehensive clinical competency curricula for hazardous drinking and substance use disorders (SUDs) exists for medical students, residents, and practicing health care providers. Evaluations of these curricula typically focus on learner attitudes and knowledge, although changes in clinical skills are of greater interest and utility. The authors present a pre-post clinical skill evaluation of a 10-hour screening, brief intervention, and referral to treatment (SBIRT) curriculum for hazardous drinking and SUDs for primary care internal medicine residents using standardized patient examinations to better determine the impact of SBIRT training on clinical practice. Residents had large improvements in history taking, substance use screening skills, SUD assessment and diagnostic skills, and in SBIRT knowledge, including documentation, systems, and diversity issues. Residents made moderate improvements in brief intervention skills. Future SBIRT curricular evaluations would ideally include a controlled comparison with larger samples from multiple institutions.

Integrating screening, brief intervention, and referral to treatment (SBIRT) into clinical practice settings: a brief review.

Screening, brief intervention, and referral to treatment (SBIRT) is a public health approach to the delivery of early intervention and treatment services for individuals at risk of developing substance use disorders (SUDs) and those who have already developed these disorders. SBIRT can be flexibly applied; therefore, it can be delivered in many clinical care settings. SBIRT has been adapted for use in hospital emergency settings, primary care centers, office- and clinic-based practices, and other community settings, providing opportunities for early intervention with at-risk substance users before more severe consequences occur. In addition, SBIRT interventions can include the provision of brief treatment for those with less severe SUDs and referrals to specialized substance abuse treatment programs for those with more severe SUDs. Screening large numbers of individuals presents an opportunity to engage those who are in need of treatment. However, additional research is needed to determine how best to implement SBIRT.

The Physician Clinical Support System-Buprenorphine (PCSS-B): a novel project to expand/improve buprenorphine treatment.

Opioid dependence is largely an undertreated medical condition in the United States. The introduction of buprenorphine has created the potential to expand access to and use of opioid agonist treatment in generalist settings. Physicians, however, often have limited training and experience providing this type of care. Some physicians believe having a mentoring relationship with an experienced provider during their initial introduction to the use of buprenorphine would ease implementation. Our goal was to describe the development, implementation, resources, and evaluation of the Physician Clinical Support System-Buprenorphine (PCSS-B), a federally funded program to improve access to and quality of treatment with buprenorphine. We provide a description of the PCSS-B, a national network of 88 trained physician mentors with expertise in buprenorphine treatment and skills in clinical education. We provide information regarding the use the PCSS-B core services including telephone, email and in-person support, a website, clinical guidances, a warmline and outreach to primary care and specialty organizations. Between July 2005 and July 2009, 67 mentors and 4 clinical experts reported providing mentoring services to 632 participants in 48 states, Washington DC and Puerto Rico. A total of 1,455 contacts were provided through email (45%), telephone (34%) and in-person visits (20%). Seventy-six percent of contacts addressed a clinical issue. Eighteen percent of contacts addressed a logistical issue. The number of contacts per participant ranged from 1-125. Between August 2005 and April 2009 there were 72,822 visits to the PCSS-B website with 179,678 pages viewed. Seven guidances were downloaded more than 1000 times. The warmline averaged more than 100 calls per month. The PCSS-B model provides support for a mentorship program to assist non-specialty physicians in the provision of buprenorphine and may serve as a model for dissemination of other types of care.

Methadone, buprenorphine, and street drug interactions with antiretroviral medications.

While street drugs appear unlikely to alter the metabolism of antiretroviral (ARV) medications, several ARVs may induce or inhibit metabolism of various street drugs. However, research on these interactions is limited. Case reports have documented life-threatening overdoses of ecstasy and gamma-hydroxybutyrate after starting ritonavir, an ARV that inhibits several metabolic enzymes. For opioid addiction, methadone or buprenorphine are the treatments of choice. Because a number of ARVs decrease or increase methadone levels, patients should be monitored for methadone withdrawal or toxicity when they start or stop ARVs. Most ARVs do not cause buprenorphine withdrawal or toxicity, even if they alter buprenorphine levels, with rare exceptions to date including atazanavir/ritonavir associated with significant increases in buprenorphine and adverse events related to sedation and mental status changes in some cases. There are newer medications yet to be studied with methadone or buprenorphine. Further, there are many frequently used medications in treatment of complications of HIV disease that have not been studied. There is need for continuing research to define these drug interactions and their clinical significance.

Indicators of buprenorphine and methadone use and abuse: what do we know?

Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues.

Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review.

Drug interactions are a leading cause of morbidity and mortality. Methadone and buprenorphine are frequently prescribed for the treatment of opioid addiction. Patients needing treatment with these medications often have co-occurring medical and mental illnesses that require medication treatment. The abuse of illicit substances is also common in opioid-addicted individuals. These clinical realities place patients being treated with methadone and buprenorphine at risk for potentially toxic drug interactions. A substantial literature has accumulated on drug interactions between either methadone or buprenorphine with other medications when ingested concomitantly by humans. This review summarizes current literature in this area.