Opioid stewardship training during the transition to residency to prepare medical students to recognize and treat opioid use disorder.

Background: With a drastic shortage of addiction medicine specialists-and an ever-growing number of patients with opioid use disorder (OUD)-there is a dire need for more clinicians to feel confident in prevention and management of OUD and obtain a DEA-X waiver to prescribe medications to treat OUD. Here we determine if it is feasible to certify 4th year medical students with DEA-X waiver training as a component of the PROUD (Prevent and Reduce Opioid Use Disorder) curriculum, and if PROUD enhanced preparedness for medical students to manage OUD as interns. Methods: We implemented a sequential mixed-methods IRB approved study to assess feasibility (completing all required components of DEA-X waiver training) and impact of PROUD (measured by knowledge growth, enhancement for residency, and utilization of training during internship). Students completed 11 hours of required OUD training. Quantitative data included pre-/post- knowledge and curriculum satisfaction assessments as well as long-term impact with follow up survey as interns. Qualitative data was collected by survey and semi-structured focus groups. Results: All 120 graduating medical students completed the required components of the curriculum. Knowledge improved on the Provider Clinical Support Services (12.9-17.3, p < 0.0001) and Brief Opioid Overdose Knowledge assessments (10.15-10.81, p < 0.0001). Course satisfaction was high: 90% recommended online modules; 85% recommended training overall. Six qualitative themes emerged: (1) curriculum content was practical, (2) online modules allowed flexibility, (3) in-person seminars ensured authenticity, (4) timing at the transition to residency was optimal, (5) curriculum enhanced awareness and confidence, and (6) training was applicable to future careers. At 3 months, 60% reported using their training during internship; 64% felt more prepared to treat OUD than peers. Conclusions: PROUD trained 4th year medical students in opioid stewardship. As interns, students felt ready to serve as change agents to prevent, diagnose, and treat OUD.

Changes in fruit and vegetable consumption in relation to changes in sleep characteristics over a 3-month period among young adults.

OBJECTIVE: To evaluate whether increases in fruit and vegetable (FV) consumption were associated with concomitant changes in insomnia symptoms, sleep duration, and quality. DESIGN: Secondary longitudinal analysis of a randomized trial, baseline to 3 months. SETTING: Integrated health care systems in Detroit, Michigan and Danville, Pennsylvania. PARTICIPANTS: About 1165 young adults who were low consumers of FV (<3 servings/day) at baseline. INTERVENTION: Online 3-arm program designed to increase FV consumption. MEASUREMENTS: We categorized FV changes into 4 categories: no change or decrease, 1 serving increase, 2 serving increase, and 3 or more serving increase. We then compared the changes in chronic insomnia classification (yes or no), sleep duration, quality, and time to fall asleep (all self-reported) across the FV change categories. Analyses were both overall and stratified by gender, adjusting for potential confounders (depression, physical activity, education, children, and study site). RESULTS: Average age ± SD was 26 ± 2.8 years (71% women). At 3-month follow-up, participants on average increased FV intake by 1.2 ± 1.4 servings. Women who increased FV intake by 3+ servings showed improvements in insomnia symptoms (2-fold higher odds of improvement; 95% CI 1.1 to 3.6), sleep quality (0.2-point higher sleep quality score; 95% CI -0.01, 0.3), and time to fall asleep (4.2 minutes; 95% CI -8, 0) compared to women who did not change or decreased their FV intake. Associations were not as apparent among men. CONCLUSION: Young women with low consumption of FV may experience improvements in insomnia-related sleep difficulties by increasing their consumption of FV.

Sleep Duration and Quality in Relation to Fruit and Vegetable Intake of US Young Adults: a Secondary Analysis.

BACKGROUND: Sleep is gaining recognition as a determinant of diet, yet this relationship remains understudied among young adults. We sought to examine how sleep duration and quality were related to fruit and vegetable (FV) intake within a diverse sample of young adults. METHODS: Participants (n = 1444) ages 21-30 (69% women, 15% African American, 35% full or part time in college) consuming < 5 servings/day of FV (eligibility criteria) completed a baseline survey to enroll in a randomized online FV intervention. Sleep questions included duration, perceived sleep quality, time to fall asleep, and insomnia symptoms. Overall and gender-stratified linear regression models compared average daily FV intake and sleep characteristics, adjusting for confounders. RESULTS: One-third (32%) of the participants reported < 7 h of sleep per night, and 36% noted insomnia symptoms ≥ 3 times per week. Women, a BMI > 30, African American race/ethnicity, less education, unemployment, higher depression, and stress were related to suboptimal sleep. Bivariate analyses showed that better sleep was associated with higher FV intake. After accounting for confounders, men with better sleep quality and shorter time to fall asleep had higher intakes of FV (1.12 serving/day difference in highest versus lowest quality [95% CI 0.48, 1.75] and a 0.52 serving/day higher intake difference for shortest versus longest fall asleep time [95% CI 0.90, 0.15], respectively). CONCLUSION: Sleep was highly prevalent in a diverse sample of community-based young adults and may contribute to lower FV intake among men. These associations highlight young adulthood as an important period for promoting healthy sleep habits.

Opioid Stewardship in Urology: Quality Improvement Summit 2018.

INTRODUCTION: We summarize the 2018 AUA (American Urological Association) Quality Improvement Summit, Opioid Stewardship in Urology, highlighting appropriate urological opioid use as well as reviewing programs that have been successful in reducing opioid prescribing. The AUA brought together nearly 100 attendees from across the United States, including clinicians who specialize in urology and other specialties, as well as researchers, government officials and others. METHODS: The 2018 AUA Quality Improvement Summit was a 1-day meeting held at AUA headquarters in Linthicum, Maryland. Talks and panels highlighted opioid stewardship programs and emphasized research on the nature and management of postoperative pain. RESULTS: The impact of the opioid epidemic is profound and the contribution of postoperative prescribing is noteworthy (eg 6% of opioid naïve patients demonstrate new persistent use habits after surgery and up to 70% of opioid pills prescribed after surgery go unused). Speakers raised awareness of these facts and detailed opportunities to improve, including prudent prescribing, opioid reclamation, use of nonopioid alternatives, and outreach and education. CONCLUSIONS: The 2018 AUA Quality Improvement Summit provided a platform for urologists to discuss the opioid epidemic and to learn strategies for combatting this issue from multidisciplinary experts. Physician led opioid stewardship and research, facilitated by this Summit, may enhance the quality and safety of medical care and improve the lives of patients, their families and their communities.

5-2-1-0 Lifestyle risk factors predict obesity in Millennials.

The Making Effective Nutritional Choices Generation Y (MENU GenY) study is a web-based intervention trial aimed at improving food choices in those aged 21-30 years. We report baseline levels of the 5-2-1-0 healthy lifestyle patterns to predict a body mass index (BMI) ≥30 vs <30 kg m-2 . Overall, 1674 young adults (69% female) from two large health systems enroled and completed an online survey asking questions about lifestyle habits. A multivariable binary logistic regression model was utilized to predict a BMI ≥30 while controlling for known predictors of obesity. Consuming >3 daily servings of fruits/vegetables (odds ratio, OR = 0.90, 95% confidence interval, CI = 0.81, 0.99), and reporting >2.5 hours/week of vigorous physical activity (OR = 0.93, 95% CI = 0.89-0.96, P < 0.001) was associated with a BMI <30. Conversely, time sitting (OR = 1.07, 95% CI = 1.04, 1.11) and consuming sugar-sweetened beverages (OR = 1.08, 95% CI = 1.00, 1.15) were related to a BMI ≥30. In this cohort of 20-30-year-olds, we observed a consistent relationship between obesity and the 5-2-1-0 healthy lifestyle patterns previously reported among children and adolescents.

Motivations of Young Adults for Improving Dietary Choices: Focus Group Findings Prior to the MENU GenY Dietary Change Trial.

BACKGROUND: Young adulthood is often associated with poor dietary habits that may increase risk of obesity and chronic diseases. As independence grows, little is known about strategies to help balance social, work, and education commitments that may override desires to incorporate healthful food choices. OBJECTIVE: In advance of a randomized trial to test an online intervention targeting young adults, we sought to identify views and experiences with healthy eating, and specifically, eating more fruits and vegetables. METHODS: We conducted 13 focus groups with 68 young adults in metropolitan Detroit (Henry Ford Health System) and rural Pennsylvania (Geisinger Health System). Randomly selected adults aged 21 to 30 years, using health system automated data, were sent recruitment letters. Questions were grounded in social cognitive theory and self-determination theory. Audiotapes were transcribed, content themes identified, coded, verified for reliability, and analyzed qualitatively. RESULTS: Young adults' efforts to eat healthfully included three major themes of (1) motivations to create a healthy lifestyle, teach by example, feel better, and manage weight and future health problems; (2) learning to eat well from childhood, independent living, and peers; and (3) strategies to eat better through planning, tracking, and commitment. DISCUSSION: We uncovered theory-based factors that facilitate healthy dietary behavior change among young adults, including managing their behavior through self-monitoring, goal-setting, small steps, meaningful reinforcements, and social opportunities. CONCLUSIONS: Targeted interventions encouraging reflection on personal values related to meaningful contemporary health benefits are likely to resonate with young adults, as will opportunities to receive and share new information.

Antipsychotic medications and extreme weight gain in two health systems.

OBJECTIVE: We conducted this study to investigate the rate of clinically important, extreme weight gain (EWG; ≥7% body weight gain) among all second generation antipsychotic (SGA) users in two large health care systems in the United States. STUDY DESIGN: Retrospective observational cohort study. METHODS: We used electronic medical record databases of two health systems to identify adults aged 18-79 years who from 1 January 2004 to 31 December 2011 had initiated a SGA medication. All patients had to have a minimum of two weight measures in the medical record: (1) one or more weights in the 180-day pre-treatment (baseline) period; and (2) one or more weights in the first year after initiating SGA treatment. RESULTS: We found that EWG occurred in 7.7-17.0% of SGA users. At one year, the average weight gain was nearly 10kg among SGA users who experienced EWG. Olanzapine was the SGA most commonly associated with EWG with a rate of 17.0 per 100 users [95% confidence interval (CI): 14.2-20.5], while ziprasidone was least commonly associated with EWG (7.7 per 100 users; 95% CI: 4.6-13.0). CONCLUSIONS: We found that clinically-important weight gain was common after the initiation of SGA treatment, and the EWG phenotype was easily identifiable within electronic medical records. There was significant heterogeneity in the rate of EWG across SGA medications. Weight gains of this magnitude are likely to have adverse health consequences and there is a significant unmet opportunity for physicians to identify these events and mitigate the harms of SGA use.

Naltrexone vs Placebo for the Treatment of Alcohol Dependence: A Randomized Clinical Trial.

IMPORTANCE: Alcohol use disorder is one of the leading causes of disability worldwide. While effective pharmacological treatments exist, they are efficacious only in certain individuals, contributing to their limited use. Secondary analysis of clinical trial data suggests that a functional polymorphism (rs1799971, Asn40Asp) of the µ-opioid receptor gene (OPRM1) is associated with the risk of relapse to heavy drinking following treatment with the opioid antagonist naltrexone. OBJECTIVE: To prospectively examine whether rs1799971 is predictive of naltrexone treatment response. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 12-week, double-blind, randomized clinical trial of naltrexone vs placebo in individuals with alcohol dependence (intent-to-treat analysis). Participants were randomly assigned to study treatment based on the presence of 1 or 2 copies of the Asp40 allele compared with those homozygous for the Asn40 allele (2 × 2 cell design). Recruitment occurred between January 2009 and September 2013. All participants were seen in an outpatient clinical setting. A convenience sample of participants (n = 221) was recruited from 5 sites. All participants met DSM-IV criteria for alcohol dependence, with no concurrent psychotic or manic symptoms, no use of concurrent psychotropic medications, and no current dependence on illicit substances. INTERVENTIONS: The study drug was naltrexone (50 mg) given once daily or corresponding placebo. MAIN OUTCOMES AND MEASURES: The primary study outcome measure was relapse to heavy drinking measured using the timeline follow-back method. RESULTS: There was no evidence of a genotype × treatment interaction on the primary outcome of heavy drinking (P = .32). In the Asn40 group, the observed effect of naltrexone was similar to that in previous trials (odds ratio, 0.69; 95% CI, 0.41-1.18; P = .17), with a very small naltrexone effect in the Asp40 group (odds ratio, 1.10; 95% CI, 0.52-2.31; P = .80), contrary to the pattern expected a priori. A significant reduction in heavy drinking occurred across all groups (P = .001). Other drinking outcomes, and all secondary outcomes, demonstrated similar time effects, with no genotype × treatment interaction. CONCLUSIONS AND RELEVANCE: The results of this study do not support the hypothesis that the Asp40 allele moderates the response to naltrexone treatment. It is premature to use the Asn40Asp polymorphism as a biomarker to predict the response to naltrexone treatment of alcohol dependence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00831272.

Treatment of adolescent obesity comparing self-guided and group lifestyle modification programs: a potential model for primary care.

Lifestyle modification programs (LMP) for weight loss in adolescents with obesity are effective but not available. Primary care may be a setting for reaching more adolescents. Two models of LMP for use in primary care were examined. Adolescents and caregivers enrolled in a 1-year randomized trial comparing Group LMP with Self-Guided LMP. All participants (N = 169) received the same treatment recommendations and met with a health coach six times in clinic. Group LMP participants had an additional 17 group sessions; those in Self-Guided LMP followed the remainder of the program at home with parental support. The primary outcome was percentage change in initial body mass index. The mean (SE) 1.31% (0.95%) reduction in Group LMP did not differ significantly from the 1.17% (0.99%) decrease in the Self-Guided LMP (p = 0.92). Both treatments were significantly effective in reducing body mass index. Given its brevity, the Self-Guided LMP offers an innovative approach for primary care.

Prevalence of prescription opioid-use disorder among chronic pain patients: comparison of the DSM-5 vs. DSM-4 diagnostic criteria.

The authors estimated the prevalence of lifetime prescription opioid-use disorder among outpatients on opioid therapy using criteria from both versions 4 and 5 of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Using electronic records from a large health care system, a random sample of outpatients undergoing long-term opioid therapy for non-cancer pain was identified and 705 participants completed diagnostic interviews. The prevalence of lifetime DSM-5 opioid-use disorder among these patients was 34.9% (95% confidence interval [CI] = 30.5?39.5), similar to the prevalence of DSM-4 opioid dependence (35.5%, 95% CI = 31.1?40.2). The Kappa value between DSM-5 and DSM-4 criteria was high (Kappa = 0.873, p < 0.0001). Logistic regressions suggested DSM-5 opioid-use disorder was associated with age younger than 65 (odds ratio [OR] = 2.25, p = 0.009), history of opioid abuse (OR = 4.94, p < 0.001), higher opioid withdrawal symptoms (OR = 3.01, p = 0.008), and history of substance abuse treatment (OR = 1.62, p = 0.015), similar to DSM-4. Based on DSM-5, 21.7% of patients met criteria for moderate and 13.2% for severe opioid-use disorder, respectively. Given the changes proposed, the finding that the prevalence of and risk factors for DSM-5 opioid-use disorders were similar to DSM-4 were unexpected. Further research is advised.

Body mass index measurement and obesity prevalence in ten U.S. health plans.

OBJECTIVE: The objective of this study was to examine the frequency of body mass index (BMI) measurement before the implementation of two new Healthcare Effectiveness Data and Information Set (HEDIS) performance measures for obesity that require U.S. health plans to annually report the frequency of BMI and BMI percentile measurement among all adults and children who had at least one outpatient visit during the past two years. DESIGN: Cross-sectional study. SETTING: A consortium of ten U.S. health plans and care delivery systems from the Health Maintenance Organization Research Network, which together provide care to more than 6.5 million adults and children. PARTICIPANTS: Children and adults, age 2 years and older, who were continuously enrolled in one of ten U.S. health plans for at least one full year from 2005 to 2006. METHODS: We extracted available anthropometric data for 3.7 million adults and 1.2 million children with at least one visit captured from ten electronic medical record databases from 2005 to 2006. RESULTS: We found that the availability of BMI measurements for adults ranged widely across health plans from 28% to 88%, and availability of BMI percentiles for children ranged from 21% to 81%. Among adults and children with BMI measures in these ten health plans, the overall prevalence of overweight and obesity were very similar to those reported in the 2005 to 2006 U.S. national surveys that used measured heights and weights. CONCLUSION: The newly approved HEDIS performance measures likely represent an important step in addressing the quality of obesity care in the United States. The current study demonstrates that these HEDIS measures are achievable, especially among health plans that have implemented electronic medical records. Future research should assess the relationship between BMI assessment, provider counseling and treatment practices, and long-term changes in obesity rates among different population groups.

Nicotinic acetylcholine receptor genes on chromosome 15q25.1 are associated with nicotine and opioid dependence severity.

A locus on chromosome 15q25.1 previously implicated in nicotine, alcohol, and cocaine dependence, smoking, and lung cancer encodes subunits of the nicotinic acetylcholine receptor (nAChR) expressed in the mesolimbic system and thought to mediate substance dependence. Opioid dependence severity (ODS), nicotine dependence severity (NDS), smoking status and quantity, and the number of attempts to quit were assessed using questionnaire instruments in 505 subjects who were prescribed opioid medications for chronic pain in outpatient practice sites. Multivariate regression was used to test for genetic association of these phenotypes with 5 SNPs in the nAChR gene cluster on chromosome 15q25.1, adjusting for background variables. A coding variant in CHRNA5 (rs16969968[A]) was significantly associated with 1.4-unit higher ODS (p < 0.00017). A variant in the 3' untranslated region of CHRNA3 (rs660652[G]) was significantly associated with 1.7-fold higher odds of lifetime smoking (p < 0.0092), 1.1-unit higher NDS (p < 0.0007), 0.7 more pack-years of cigarette smoking (p < 0.0038), and 0.8 more lifetime attempts to quit (p < 0.0084). Our data suggest an association of DNA variants in the nAChR gene cluster on chromosome 15q25.1 with ODS, as well as NDS and related smoking phenotypes. While the association of this locus with NDS and smoking phenotypes is well known, the association with ODS, a dimension of opioid substance dependence, is novel and requires verification in independent studies.

Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system.

AIMS: Our study sought to assess the prevalence of and risk factors for opioid drug dependence among out-patients on long-term opioid therapy in a large health-care system. METHODS: Using electronic health records, we identified out-patients receiving 4+ physician orders for opioid therapy in the past 12 months for non-cancer pain within a large US health-care system. We completed diagnostic interviews with 705 of these patients to identify opioid use disorders and assess risk factors. RESULTS: Preliminary analyses suggested that current opioid dependence might be as high as 26% [95% confidence interval (CI) = 22.0-29.9] among the patients studied. Logistic regressions indicated that current dependence was associated with variables often in the medical record, including age <65 [odds ratio (OR) = 2.33, P = 0.001], opioid abuse history (OR = 3.81, P < 0.001), high dependence severity (OR = 1.85, P = 0.001), major depression (OR = 1.29, P = 0.022) and psychotropic medication use (OR = 1.73, P = 0.006). Four variables combined (age, depression, psychotropic medications and pain impairment) predicted increased risk for current dependence, compared to those without these factors (OR = 8.01, P < 0.001). Knowing that the patient also had a history of severe dependence and opioid abuse increased this risk substantially (OR = 56.36, P < 0.001). CONCLUSION: Opioid misuse and dependence among prescription opioid patients in the United States may be higher than expected. A small number of factors, many documented in the medical record, predicted opioid dependence among the out-patients studied. These preliminary findings should be useful in future research efforts.

Maintenance of weight loss in adolescents: current status and future directions.

There is a dearth of research on the long-term efficacy and safety of treatments for adolescent obesity. This narrative review examined several approaches to treatment, focusing on long-term effectiveness data in adolescents, as well as relevant findings from studies of adults. The available research suggests that lifestyle modification has promise in obese adolescents, although it is not clear that any particular dietary or physical activity approach is more effective than another. Meal replacements are quite effective in adults and deserve further research in adolescents. Extending the length of treatment to teach weight loss maintenance skills is likely to improve long-term outcomes in adolescents, and delivering treatment via the Internet or telephone is a novel way of doing so. Treatment that combines lifestyle modification with the medication orlistat generally appears to be safe but only marginally superior to lifestyle modification alone. More research is needed on the management of adolescent obesity, which has been overlooked when compared with research on the treatment of obesity in children and adults.

Cost-effectiveness of pharmacogenetic testing to tailor smoking-cessation treatment.

We evaluated the cost-effectiveness of a range of smoking cessation drug treatments, including varenicline, transdermal nicotine (TN), bupropion and the use of a genetic test to choose between TN and bupropion. We performed Monte Carlo simulation with sensitivity analysis, informing analyses with published estimates of model parameters and current prices for genetic testing and smoking-cessation therapy. The primary outcomes were discounted life-years (LY) and lifetime tobacco-cessation treatment costs. In the base case, varenicline treatment was optimal with an ICER, compared to bupropion, of $2985/LY saved. In sensitivity analyses, varenicline was in all cases (and bupropion in most cases) admissible; only under favorable assumptions was the genetically tailored approach competitive. Our data suggest that an untailored approach of treatment with either bupropion or varenicline is a cost-effective form of tobacco dependence treatment, but a tailored approach for selecting between TN and bupropion can be cost-effective under plausible assumptions.

Genetic variation in mu-opioid-receptor-interacting proteins and smoking cessation in a nicotine replacement therapy trial.

Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy, we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins, namely ARRB2 and HINT1. Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label randomized trial. In a logistic regression model controlling for OPRM1 genotype, treatment type, and other covariates, we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up. Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up, but this may not be a pharmacogenetic effect, given that the participants were drug free during this time. Haplotype analysis did not reveal any significant associations for either gene. We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance; however, interpretation of this finding is limited by the small number of participants with the minor alleles for both genes. Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation, further exploration of opioid pathway genes in larger prospective pharmacogenetic trials may be warranted.

Translating basic science to improve pharmacotherapy for nicotine dependence.

Nicotine dependence has a complex multifactorial etiology, underscoring the value of applying a transdisciplinary research model. The important goal of treating nicotine dependence can be realized by transdisciplinary research that translates discoveries in basic neuroscience, pharmacology, genetics, and behavioral science to develop new treatment models that can be translated readily into the clinic and community. As part of this special issue highlighting work at the Transdisciplinary Tobacco Use Research Centers (TTURCs), we describe transdisciplinary research at the University of Pennsylvania TTURC aimed at elucidating the neurobiological and genetic basis of nicotine dependence, the development of novel medications, and the translation of this research to practice.

Smoking cessation treatment by primary care physicians: An update and call for training.

BACKGROUND: Public health and government organizations have invested considerably to increase physician adherence to smoking-cessation practice guidelines. METHODS: A random sample of 2000 U.S. primary care physicians was ascertained from the American Medical Association (AMA) in 2002. Respondents (n = 1120, 62.3%) provided self-reported data about individual and practice characteristics and smoking-cessation practices. Data were analyzed in 2005. RESULTS: Most primary care physicians (75%) advised cessation, 64% recommended nicotine patches, 67% recommended bupropion, 32% recommended nicotine gum, 10% referred to cessation experts, and 26% referred to cessation programs "often or always." Advising cessation was related to being older, having a faculty appointment, having trained staff for smoking counseling, and having confidence to counsel patients about smoking. Physicians who were internists, younger, and those with greater confidence to counsel patients about smoking recommended nicotine replacement more often. Prescribing bupropion was less common among older physicians, in the Northeast, with trained staff available for counseling, and with a greater proportion of minority or Medicaid patients. Prescribing bupropion was more common among AMA-member physicians and physicians with greater confidence to counsel patients about smoking. Providing a referral to an outside expert or program was more common among female physicians, and physicians in the Northeast or West, with larger clinical practices, and with trained staff for cessation counseling. CONCLUSIONS: Current physician self-reported practices for smoking cessation suggest opportunity for improvement. Targeted efforts to educate and support subsets of primary care physicians may improve physician adherence and smoking outcomes.

Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials.

Although bupropion and nicotine replacement therapy (NRT) are efficacious tobacco dependence treatments, there is substantial interindividual variability in therapeutic response and most smokers relapse. Pharmacogenetics research may improve treatment outcomes by identifying genetic variants predictive of therapeutic response. We investigated the roles of two functional genetic variants in the dopamine D2 receptor (DRD2) gene in response to pharmacotherapy for tobacco dependence among participants in two randomized clinical trials with a 6-month follow-up period: a double-blind placebo-controlled trial of bupropion (n=414) and an open label trial of transdermal nicotine vs nicotine nasal spray (n=368). At the end of the treatment phase, a statistically significant (p=0.01) interaction between the DRD2 - 141C Ins/Del genotype and treatment indicated a more favorable response to bupropion among smokers homozygous for the Ins C allele compared to those carrying a Del C allele. By contrast, smokers carrying the Del C allele had statistically significantly (p=0.006) higher quit rates on NRT compared to those homozygous for the Ins C allele, independent of NRT type. The C957T variant was also associated (p=0.03) with abstinence following NRT. These results suggest that bupropion may be the preferred pharmacologic treatment for smokers homozygous for the DRD2 - 141 Ins C allele, while NRT may be more beneficial for those who carry the Del C allele. Study findings require confirmation in additional larger samples before they are applied in practice.