Jeanette M. Tetrault

Varenicline Reduces Alcohol Self-Administration in Heavy-Drinking Smokers

BACKGROUND Alcohol and tobacco dependence are highly comorbid disorders, with preclinical evidence suggesting a role for nicotinic acetylcholine receptors (nAChRs) in alcohol consumption. Varenicline, a partial nicotinic agonist with high affinity for the alpha4beta2 nAChR receptor, reduced ethanol intake in rodents. We aimed to test whether varenicline would reduce alcohol consumption and alcohol craving in humans. METHODS This double-blind, placebo-controlled investigation examined the effect of varenicline (2 mg/day vs. placebo) on alcohol self-administration using an established laboratory paradigm in non-alcohol-dependent heavy drinkers (n = 20) who were daily smokers. Following 7 days of medication pretreatment, participants were first administered a priming dose of alcohol (.3 g/kg) and subjective, and physiologic responses were assessed. A 2-hour alcohol self-administration period followed during which participants could choose to consume up to 8 additional drinks (each .15 g/kg). RESULTS Varenicline (.5 +/- SE = .40) significantly reduced the number of drinks consumed compared to placebo (2.60 +/- SE = .93) and increased the likelihood of abstaining from any drinking during the self-administration period. Following the priming drink, varenicline attenuated alcohol craving and reduced subjective reinforcing alcohol effects (high, like, rush, feel good, intoxicated). Adverse events associated with varenicline were minimal and, when combined with alcohol, produced no significant effects on physiologic reactivity, mood, or nausea. CONCLUSIONS This preliminary investigation demonstrated that varenicline significantly reduced alcohol self-administration and was well tolerated, alone and in combination with alcohol in heavy-drinking smokers. Varenicline should be investigated as a potential treatment for alcohol use disorders.

Integrating Buprenorphine Treatment into Office-based Practice: a Qualitative Study

BACKGROUNDDespite the availability and demonstrated effectiveness of office-based buprenorphine maintenance treatment (BMT), the systematic examination of physicians’ attitudes towards this new medical practice has been largely neglected.OBJECTIVETo identify facilitators and barriers to the potential or actual implementation of BMT by office-based medical providers.DESIGNQualitative study using individual and group semi-structured interviews.PARTICIPANTSTwenty-three practicing office-based physicians in New England.APPROACHInterviews were audiotaped, transcribed, and entered into a qualitative software program. The transcripts were thematically coded using the constant comparative method by a multidisciplinary team.RESULTSEighty percent of the physicians were white; 55% were women. The mean number of years since graduating medical school was 14 (SD = 10). The primary areas of clinical specialization were internal medicine (50%), infectious disease (20%), and addiction medicine (15%). Physicians identified physician, patient, and logistical factors that would either facilitate or serve as a barrier to their integration of BMT into clinical practice. Physician facilitators included promoting continuity of patient care, positive perceptions of BMT, and viewing BMT as a positive alternative to methadone maintenance. Physician barriers included competing activities, lack of interest, and lack of expertise in addiction treatment. Physicians’ perceptions of patient-related barriers included concerns about confidentiality and cost, and low motivation for treatment. Perceived logistical barriers included lack of remuneration for BMT, limited ancillary support for physicians, not enough time, and a perceived low prevalence of opioid dependence in physicians’ practices.CONCLUSIONSAddressing physicians’ perceptions of facilitators and barriers to BMT is crucial to supporting the further expansion of BMT into primary care and office-based practices.

A Meta-analysis of the Efficacy of Nonphysician Brief Interventions for Unhealthy Alcohol Use: Implications for the Patient-Centered Medical Home

Brief physician interventions can reduce alcohol consumption. Physicians may not have the time to provide brief interventions, and it is unclear whether nonphysicians can do so effectively. We conducted a systematic review and meta-analysis to examine the efficacy of brief interventions by nonphysician clinicians for unhealthy alcohol use. We searched the English-language literature in MEDLINE and other databases covering the domains of alcohol problems, primary care, nonphysician, and brief interventions. Studies of brief interventions delivered at least in part by nonphysicians in primary care and examining drinking outcomes were included. Sensitivity analyses examined the effect of excluding studies that contributed disproportionately to the heterogeneity of results. Thirteen studies, conducted 1996-2008, met our criteria. Seven studies with a total of 2,633 patients were included in the meta-analysis. Nonphysician interventions were associated with 1.7 (95% confidence interval [CI]=-.03 to -3.5) fewer standard drinks per week than control conditions (p = .054). Excluding the one study that increased heterogeneity, the effect was smaller but reached statistical significance; nonphysician counseling was associated with 1.4 (95% CI = .3- 2.4) fewer standard drinks per week compared to control (p = .012). Nonphysician brief interventions are modestly effective at reducing drinking in primary care patients with unhealthy alcohol use.

Developing and Validating a Human Laboratory Model to Screen Medications for Smoking Cessation

INTRODUCTION To facilitate translational work in medications development for smoking cessation, we have developed a human laboratory analogue of smoking lapse behavior. Our paradigm models 2 critical features of smoking lapse: the ability to resist the first cigarette and subsequent ad libitum smoking. In this paper we present the results of 2 studies designed to develop and validate the effect of nicotine deprivation on smoking lapse behavior. METHODS Study 1 (n = 30) was designed to develop the model parameters by examining varying levels of nicotine deprivation (1, 6, and 18 hr; within-subject) and identifying optimum levels of monetary reinforcement to provide while modeling the ability to resist smoking. Study 2 was designed to validate the model by screening smoking cessation medications with known clinical efficacy. Subjects (n = 62) were randomized to either varenicline 2 mg/day, bupropion 300 mg/day, or placebo, and we then modeled their ability to resist smoking and subsequent ad libitum smoking. RESULTS In Study 1, increasing levels of nicotine deprivation and decreasing levels of monetary reinforcement decreased the ability to resist smoking. In Study 2, the lapse model was found to be sensitive to medication effects among smokers who demonstrated a pattern of heavy, uninterrupted, and automated smoking (i.e., smoked within 5 min of waking). Ratings of craving, mood, withdrawal, and subjective cigarette effects are presented as secondary outcomes with results mirroring clinical findings. CONCLUSIONS Our smoking lapse model demonstrates promise as a translational tool to screen novel smoking cessation medications. Next steps in this line of research will focus on evaluating predictive validity.

Current and potential pharmacological treatment options for maintenance therapy in opioid-dependent individuals.

Opioid dependence, manifesting as addiction to heroin and pharmaceutical opioids is increasing. Internationally, there are an estimated 15.6 million illicit opioid users. The global economic burden of opioid dependence is profound both in terms of HIV and hepatitis C virus transmission, direct healthcare costs, and indirectly through criminal activity, absenteeism and lost productivity. Opioid agonist medications, such as methadone and buprenorphine, that stabilize neuronal systems and provide narcotic blockade are the most effective treatments. Prolonged provision of these medications, defined as maintenance treatment, typically produces improved outcomes when compared with short-duration tapers and withdrawal. The benefits of opioid agonist maintenance include decreased illicit drug use, improved retention in treatment, decreased HIV risk behaviours and decreased criminal behaviour. While regulations vary by country, these medications are becoming increasingly available internationally, especially in regions experiencing rapid transmission of HIV due to injection drug use. In this review, we describe the rationale for maintenance treatment of opioid dependence, discuss emerging uses of opioid antagonists such as naltrexone and sustained-release formulations of naltrexone and buprenorphine, and provide a description of the experimental therapies.

Previous Use of Alcohol, Cigarettes, and Marijuana and Subsequent Abuse of Prescription Opioids in Young Adults

PURPOSE There has been an increase in the abuse of prescription opioids, especially in younger individuals. The current study explores the association between alcohol, cigarette, and/or marijuana use during adolescence and subsequent abuse of prescription opioids during young adulthood. METHODS We used demographic/clinical data from community-dwelling individuals in the 2006-2008 National Survey on Drug Use and Health. We used logistic regression analyses, adjusted for these characteristics, to test whether having previous alcohol, cigarette, or marijuana use was associated with an increased likelihood of subsequently abusing prescription opioids. RESULTS Twelve percent of the survey population of 18-25 year olds (n = 6,496) reported current abuse of prescription opioids. For this population, prevalence of previous substance use was 57% for alcohol, 56% for cigarettes, and 34% for marijuana. We found previous alcohol use was associated with the subsequent abuse of prescription opioids in young men but not young women. Among both men and women, previous marijuana use was 2.5 times more likely than no previous marijuana to be associated with subsequent abuse of prescription opioids. We found that among young boys, all previous substance use (alcohol, cigarettes, and marijuana), but only previous marijuana use in young girls, was associated with an increased likelihood of subsequent abuse of prescription opioids during young adulthood. CONCLUSIONS Previous alcohol, cigarette, and marijuana use were each associated with current abuse of prescription opioids in 18-25-year-old men, but only marijuana use was associated with subsequent abuse of prescription opioids in young women. Prevention efforts targeting early substance abuse may help to curb the abuse of prescription opioids.

Substance Abuse and Withdrawal in the Critical Care Setting

Substance use is common among individuals admitted to the critical care setting and may complicate treatment of underlying disorders. It is imperative for the critical care team to have a high index of suspicion for substance intoxication and withdrawal. This article reviews the epidemiology of substance use in this population and the treatment of common withdrawal syndromes. General principles regarding the management of substance withdrawal syndromes include general resuscitative measures, use of a symptom-triggered approach, and substitution of a long-acting replacement for the abused drug in gradual tapering dose. The authors stress the importance of long-term planning as part of the overall treatment protocol beyond the acute presentation.

Developing and Implementing a Multispecialty Graduate Medical Education Curriculum on Screening, Brief Intervention, and Referral to Treatment (SBIRT)

The authors sought to evaluate the feasibility and acceptability of initiating a Screening, Brief Intervention, and Referral to Treatment (SBIRT) for alcohol and other drug use curriculum across multiple residency programs. SBIRT project faculty in the internal medicine (traditional, primary care internal medicine, medicine/pediatrics), psychiatry, obstetrics and gynecology, emergency medicine, and pediatrics programs were trained in performing and teaching SBIRT. The SBIRT project faculty trained the residents in their respective disciplines, accommodating discipline-specific implementation issues and developed a SBIRT training Web site. Post-training, residents were observed performing SBIRT with a standardized patient. Measurements included number of residents trained, performance of SBIRT in clinical practice, and training satisfaction. One hundred and ninety-nine residents were trained in SBIRT: 98 internal medicine, 35 psychiatry, 18 obstetrics and gynecology, 21 emergency medicine, and 27 pediatrics residents. To date, 338 self-reported SBIRT clinical encounters have occurred. Of the 196 satisfaction surveys completed, the mean satisfaction score for the training was 1.60 (1 = very satisfied to 5 = very dissatisfied). Standardized patient sessions with SBIRT project faculty supervision were the most positive aspect of the training and length of training was a noted weakness. Implementation of a graduate medical education SBIRT curriculum in a multispecialty format is feasible and acceptable. Future efforts focusing on evaluation of resident SBIRT performance and sustainability of SBIRT are needed.

Hepatic Safety and Antiretroviral Effectiveness in HIV-Infected Patients Receiving Naltrexone

BACKGROUND We sought to determine the impact of naltrexone on hepatic enzymes and HIV biomarkers in HIV-infected patients. METHODS We used data from the Veterans Aging Cohort Study-Virtual Cohort, an electronic database of administrative, pharmacy, and laboratory data. We restricted our sample to HIV-infected patients who received an initial oral naltrexone prescription of at least 7 days duration. We examined aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and HIV biomarker (CD4 and HIV RNA) values for the 365 days prior to, during, and for the 365 days post-naltrexone prescription. We also examined cases of liver enzyme elevation (LEE; defined as >5 times baseline ALT or AST or >3.5 times baseline if baseline ALT or AST was >40 IU/l). RESULTS Of 114 HIV-infected individuals, 97% were men, 45% white, 57% Hepatitis C co-infected; median age was 49 years; 89% of the sample had a history of alcohol dependence and 32% had opioid dependence. Median duration of naltrexone prescription was 49 (interquartile range 30 to 83) days, representing 9,525 person-days of naltrexone use. Mean ALT and AST levels remained below the upper limit of normal. Two cases of LEE occurred. Mean CD4 count remained stable and mean HIV RNA decreased after naltrexone prescription. CONCLUSIONS In HIV-infected patients, oral naltrexone is rarely associated with clinically significant ALT or AST changes and does not have a negative impact on biologic parameters. Therefore, HIV-infected patients with alcohol or opioid dependence can be treated with naltrexone.

Brief versus extended counseling along with buprenorphine/naloxone for HIV-infected opioid dependent patients

Untreated opioid dependence adversely affects HIV outcomes. Integrating buprenorphine/naloxone into HIV treatment settings is feasible; however, the optimal level of counseling has not been established. We conducted a 12-week randomized clinical trial of physician management (PM) versus PM plus enhanced medical management (EMM) in 47 subjects. At 12 weeks, there were no differences between the two groups in percentage of opioid negative urines (63.6% PM vs. 69.0% PM+EMM, p=.5), maximum duration of continuous abstinence (4.9 weeks PM vs. 5.2 weeks PM+EMM, p=.8) or retention (80% PM vs. 59% PM+EMM, p=.1). The percentage of subjects with detectable HIV viral loads decreased from 58% at baseline to 40% at 12 weeks across both groups (p=.02 for time) with no between group differences (p=.84 and p=.27 for the interaction). Providing more extensive counseling beyond PM is feasible in an HIV clinic, but we are unable to detect an improvement in outcomes associated with these services.