Sleep as an Important Target or Modifier in Alcohol Use Disorder Clinical Treatment: Example From a Recent Gabapentin Randomized Clinical Trial.

OBJECTIVES: Alcohol consumption affects sleep both in healthy populations and in patients with alcohol use disorder (AUD). However, sleep has typically not been considered within AUD pharmacotherapy trials. We used data from a completed gabapentin clinical treatment trial to explore the medication's effect on patient-rated insomnia measured by a standard insomnia rating (Insomnia Severity Index [ISI]) and whether this influenced gabapentin's effects on alcohol consumption. METHODS: This study included 90 individuals with current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition AUD criteria reporting current or past alcohol withdrawal. Participants were assigned to placebo or gabapentin (up to 1200 mg/day) for a 16-week randomized controlled trial with percent heavy drinking days (PHDD) and percent abstinent days (PDA) as outcomes. Utilizing mixed-effects models, this study assessed medication effects on ISI over the trial. We then examined the interaction of baseline ISI and medication on drinking. Finally, given our previous finding of alcohol withdrawal influencing gabapentin efficacy, we added change in ISI as a potential "moderator" of the interaction of medication effects and alcohol withdrawal on drinking. RESULTS: Sleep (ISI) improved more in those treated with gabapentin (60.6% reduction) compared with placebo (37.8% reduction; P = 0.013). Higher baseline ISI predicted drinking in gabapentin-treated individuals (lower PHDD [P = 0.026] and higher (PDA [P = 0.047]). ISI was an independent predictor of PHDD decrease and PDA increase (P < 0.001; P = 0.002), but this did not significantly moderate gabapentin's effectiveness. CONCLUSIONS: Although gabapentin positively impacts both alcohol use and sleep, its effect on drinking is not fully dependent on sleep improvement, implying a direct biological mechanism on alcohol use.

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study.

Background: Alcohol use disorder (AUD) is associated with elevated brain response to cues. Recent studies have suggested that theta burst stimulation (TBS) to the medial prefrontal cortex (MPFC) can decrease reactivity to cues in a transdiagnostic manner. The goal of this clinical trial was to evaluate the effect of continuous TBS as a tool to decrease drinking behavior and brain reactivity to alcohol cues among individuals with AUD. Methods: A total of 50 individuals with AUD were recruited from an intensive outpatient treatment program. Using a randomized, double-blind, sham-controlled design, participants received 10 sessions of continuous TBS (left frontal pole, 1 session/10 days, 110% resting motor threshold, 3600 pulse/session, cue provocation before and during session). Brain reactivity to alcohol cues was acquired at four time points: at baseline and after all TBS sessions (1 month, 2 months, and 3 months). Results: Overall, 80% of the participants completed all TBS sessions. Individuals who received real TBS were 2.71 times more likely to remain enrolled in the study after 3 months and 3.09 times more likely to remain sober 3 months after treatment initiation. Real TBS also led to a significantly greater reduction in brain reactivity to alcohol cues, specifically a reduction in MPFC-striatum and MPFC-insula connectivity 2 and 3 months after TBS treatment. Conclusions: Ten days of MPFC TBS is well tolerated, reduces drinking, and decreases brain reactivity to alcohol cues for up to 3 months after treatment initiation. These results pave a critical next step in the path toward developing transcranial magnetic stimulation as an intervention for AUD and disorders associated with elevated cue reactivity.

Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone.

Alcohol Use Disorder (AUD) is characterized by loss of control over drinking. Behavioral control is mediated, in part, by cortical dopamine signaling. Inhibition of catechol-O-methyltransferase (COMT), the enzyme primarily responsible for cortical dopamine inactivation, may increase cortical dopamine, especially among individuals with genetically mediated lower dopaminergic tone, such as COMT rs4680 (val158met) val-allele homozygotes. This study was a randomized, placebo-controlled, pharmacogenetic trial of the COMT inhibitor tolcapone. Ninety non-treatment-seeking AUD individuals were prospectively genotyped for rs4680 and randomized to tolcapone (200 mg t.i.d.) or placebo for 8 days. At baseline and on day 7, peripheral COMT activity was assayed, and participants completed an fMRI alcohol cue-reactivity task; on day 8, they completed a bar-lab paradigm. Primary outcomes were: (1) natural drinking during the medication period; (2) alcohol self-administration in the bar lab; and (3) alcohol cue-elicited cortical (right inferior frontal gyrus [rIFG]) and ventral striatal activation. At baseline, the rs4680 val-allele had an additive effect on COMT activity. Tolcapone, relative to placebo, reduced COMT activity in all genotype groups. COMT genotype moderated tolcapone's effect on drinking during the medication period and in the bar lab, such that tolcapone, relative to placebo, reduced drinking only among val-allele homozygotes. Tolcapone did not affect cue-elicited ventral striatal activation but reduced rIFG activation; less rIFG activation on day 7 was associated with less drinking during the medication period. Taken together, these data suggest that COMT inhibition may reduce drinking specifically among individuals genetically predisposed to excessive COMT activity and potentially low cortical dopamine tone.ClinicalTrials.gov identifier: NCT02949934 https://clinicaltrials.gov/ct2/show/NCT02949934.

A preliminary investigation of the role of intraindividual sleep variability in substance use treatment outcomes.

INTRODUCTION: Poor sleep health is common among individuals in early treatment for substance use disorders (SUDs) and may serve an important role in predicting SUD outcomes. However, sleep parameters have been inconsistently linked with risk of relapse, perhaps because previous research has focused on mean values of sleep parameters (e.g., total sleep time [TST], sleep efficiency [SE], and sleep midpoint [SM]) across multiple nights rather than night-to-night fluctuations (i.e., intraindividual variability [IIV]). The current study assessed sleep across the first week of SUD treatment, with the aim of prospectively examining the relationship between mean and IIV of TST, SE, and SM and treatment completion and relapse within one-month post-treatment. METHODS: Treatment-seeking adults (N = 23, Mage = 40.1, 39% female) wore an actigraph to assess sleep for one week at the beginning of an intensive outpatient program treatment. Electronic medical record and follow-up interviews were utilized to determine treatment outcomes. RESULTS: Greater IIV in TST was associated with higher odds of relapse (OR = 3.55, p =.028). Greater IIV in SM was associated with lower odds of treatment completion, but only when removing mean SM from the model (OR = 0.75, p =.046). DISCUSSION: Night-to-night variability in actigraphy-measured TST is more strongly associated with SUD treatment outcomes than average sleep patterns across the week. Integrating circadian regulation into treatment efforts to improve SUD treatment outcomes may be warranted. Given the small sample size utilized in the present study, replication of these analyses with a larger sample is warranted.

The Drug Abuse Research Training (DART) Program for Psychiatry Residents and Summer Fellows: 15-Year Outcomes.

OBJECTIVE: To increase the number of physician-scientists in research, the Drug Abuse Research Training (DART) program at the Medical University of South Carolina offers a 2-year research track for psychiatry residents and a 10-week summer fellowship for students. The goal of this study was to examine program outcomes and alumni diversity levels over DART's 15-year history. METHODS: To date, 215 trainees (44 residents, 171 summer fellows) have completed the program. An anonymous online survey was sent to the 143 program alumni with valid contact information. Survey data included demographic characteristics, post-program research involvement, and self-reported barriers to continued research engagement. RESULTS: Overall survey completion response was 83.5% (N = 122). The alumni included 59.0% women, and 36.1% of respondents identified as a member of a minority racial/ethnic group. Following program completion, 77.0% of the alumni reported continued research involvement. More than half of the alumni reported scientific publications (57.4%) and conference presentations (63.1%) since completing DART. Among respondents who did not subsequently engage in research, the most common modifiable barriers included difficulty finding a mentor, self-perceived deficits in statistical skills and research methodology, and overall lack of confidence in research ability. CONCLUSIONS: Over the past 15 years, the DART program has established a diverse research training program that now spans the educational spectrum from undergraduate to residency training. Future program goals include additional training to address self-reported modifiable research barriers. This program provides a model for other training programs designed to cultivate research interests and promote the diversity of clinical researchers.

Sleep and substance use disorder treatment: A preliminary study of subjective and objective assessment of sleep during an intensive outpatient program.

BACKGROUND AND OBJECTIVES: Characteristics of sleep concerns and their relationship to mental health in heterogeneous substance use disorder (SUD) treatment settings are not well understood. The purpose of this preliminary study was to assess sleep using subjective and objective measures at two time points during SUD treatment and compare sleep changes to changes in mental health measures. METHODS: Treatment-seeking participants completed an assessment battery at the beginning of treatment (Time 1, N = 30) and again upon treatment completion (Time 2, approximately 4 weeks later, N = 22). The majority of participants were White (80%), male (63%), and presenting for alcohol use disorder (60.0%), though almost half reported polysubstance abuse (43%). Comorbidity was common (53%). Sleep and mental health questionnaires with 1 week of actigraphy and sleep diaries were completed at both time points. RESULTS: Most participants met the criteria for a sleep disorder and mean scores on questionnaires showed poor sleep quality, insomnia symptoms, and frequent nightmares, with sleep quality and insomnia improving over time but remaining clinically significant. Nightmares did not improve. Actigraphy indicated poor sleep at both time points. Improvement in insomnia was related to improvement in measures of mental health while changes in actigraphy variables were not related to these measures. DISCUSSION AND CONCLUSIONS: Multiple types of sleep disturbance are prevalent in this population, with nightmares persisting throughout treatment and insomnia symptoms showing a relationship with mental health symptoms. SCIENTIFIC SIGNIFICANCE: This was the first study to longitudinally assess mental health with subjective and objective measures of sleep across multiple types of SUDs in a community SUD treatment setting.

Opioid and Dopamine Genes Interact to Predict Naltrexone Response in a Randomized Alcohol Use Disorder Clinical Trial.

BACKGROUND: While the opiate antagonist, naltrexone, is approved for treating alcohol use disorder (AUD), not everyone who receives the medication benefits from it. This study evaluated whether the OPRM1 SNP rs1799971 interacts with the dopamine transporter gene DAT1/SLC6A3 VNTR rs28363170 or the catechol-O-methyltransferase (COMT) gene SNP rs4680 in predicting naltrexone response. METHODS: Individuals who met DSM-IV alcohol dependence were randomly assigned to naltrexone (50 mg/d) or placebo based on their OPRM1 genotype (75 G-allele carriers and 77 A-allele homozygotes) and also genotyped for DAT1 VNTR (9 vs. 10 repeats) or COMT SNP (val/val vs. met carriers). Heavy drinking days (%HDD) were evaluated over 16 weeks and at the end of treatment. Effect sizes (d) for naltrexone response were calculated based on genotypes. RESULTS: Naltrexone, relative to placebo, significantly reduced %HDD among OPRM1 G carriers who also had DAT1 10/10 (p = 0.021, d = 0.72) or COMT val/val genotypes (p = 0.05, d = 0.80), and to a lesser degree in those OPRM1 A homozygotes who were also DAT1 9-repeat carriers (p = 0.09, d = 0.70) or COMT met carriers (p = 0.03, d = 0.63). All other genotype combinations showed no differential response to naltrexone. Diarrhea/abdominal pain was more prominent in OPRM1 A homozygotes who were also DAT 9 or COMT met carriers. CONCLUSIONS: These results suggest that individuals with AUD with a more opioid-responsive genotype (OPRM1 G carriers) respond better to naltrexone if they have genotypes indicating normal/less dopamine tone (DAT1 10,10 or COMT val,val), while those with a less responsive opioid-responsive genotype (OPRM1 A homozygotes) respond better to naltrexone if they have genotypes indicating greater dopamine tone (DAT1 9-repeat or COMT met carriers). These results could lead to more personalized AUD treatments.

Insomnia severity during early abstinence is related to substance use treatment completion in adults enrolled in an intensive outpatient program.

BACKGROUND: Insomnia and other types of sleep disturbance are highly prevalent during withdrawal across many different types of substance use disorders (SUDs). It is largely unknown how sleep impacts SUD treatment outcomes, including treatment completion. METHODS: A retrospective chart review was conducted to obtain information about sleep disturbance and treatment completion in individuals beginning an intensive outpatient (IOP) SUD treatment program. Demographic data were collected along with number of sessions completed, treatment completion, comorbid psychiatric diagnosis, pertinent lab results, and scores on three self-reported measures of sleep: the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). RESULTS: Pertinent information was available for 110 individuals. The majority had clinically significant scores on the ISI and PSQI but not the ESS. ISI, but not PSQI or ESS, was associated with treatment completion, such that those with more insomnia were less likely to complete treatment. CONCLUSION: The high prevalence of insomnia symptoms and poor sleep quality coupled with the relationship between insomnia severity and treatment completion may indicate that more severe symptoms of insomnia are a risk factor for treatment completion and subsequent relapse across many substance types. Applying evidence-based insomnia interventions in SUD treatment programs may have meaningful implications for outcomes.

Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence.

BACKGROUND: The opioid antagonist naltrexone is not efficacious for every alcohol treatment seeker. However, various individual factors, such as genetic differences and nicotine-use/smoking status, have been suggested as predictors of naltrexone response. In a randomized clinical trial, we previously reported that nicotine-use/smoking status might be a stronger predictor of naltrexone efficacy than OPRM1 A118G single nucleotide polymorphism (SNP) genotype. In this report, we further characterize the nicotine-users in that trial, examine other drinking outcomes, examine the influence of smoking change on naltrexone effects on drinking, and validate the result in smokers with disialo carbohydrate-deficient transferrin (%dCDT) change as an independent biomarker of response. METHODS: Individuals (n = 146) meeting DSM-IV criteria for alcohol dependence who were genotyped for the OPRM1 A118G SNP and who did, or did not, use nicotine/cigarettes were randomized, in a balanced fashion, to naltrexone (50 mg/d) or placebo and provided medical management (MM) over a 16-week clinical trial. Alcohol use and smoking during the trial were assessed and analyzed. RESULTS: Nicotine-use/smoking status significantly interacted with medication in reducing percent heavy drinking days (PHDD) during the trial (p = 0.003), such that nicotine-users/smokers showed significantly lower PHDD on naltrexone versus placebo (p = 0.0001, Cohen's d = 0.89), while nonusers showed no significant difference between naltrexone and placebo (p = 0.95, Cohen's d = 0.02). Similar effects were shown for drinks per day and percent days drinking. The superiority of naltrexone over placebo on PHDD reduction in nicotine-users/smokers was confirmed with %dCDT (Cohen's d range 0.3 to 0.9 over the study). Naltrexone did not significantly change cigarette use in smokers, and change in use did not influence naltrexone's effect on PHDD. CONCLUSIONS: These data confirm past findings that naltrexone is more efficacious in those who use nicotine/cigarettes. Compared to previous work on the OPRM1 A118G SNP, it appears that nicotine-use might be a more salient predictor of naltrexone treatment response. While naltrexone did not change cigarette use during the study, and smoking change was not related to alcohol reduction, it should be noted that participants were not seeking smoking cessation and MM did not address this issue.

Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain Activation, OPRM1 Genotype, and Smoking Status.

This corrects the article DOI: 10.1038/npp.2017.74.

Predictors of Naltrexone Response in a Randomized Trial: Reward-Related Brain Activation, OPRM1 Genotype, and Smoking Status.

Naltrexone reduces drinking among individuals with alcohol use disorders (AUDs), but it is not effective for everyone. Variability in its effects on reward-related brain activation, genetic variation, and/or cigarette smoking may account for this mixed response profile. This randomized clinical trial tested the effects of naltrexone on drinking and alcohol cue-elicited brain activation, evaluated whether OPRM1 A118G genotype or smoking moderated these effects, and explored whether the effects of medication on cue-elicited activation predicted subsequent drinking. One hundred and fifty-two treatment-seeking individuals with alcohol dependence, half preselected to carry at least one A118G G (Asp) allele, were randomized to naltrexone (50 mg) or placebo for 16 weeks and administered an fMRI alcohol cue reactivity task at baseline and after 2 weeks of treatment. Naltrexone, relative to placebo, significantly reduced alcohol cue-elicited activation of the right ventral striatum (VS) between baseline and week 2 and reduced heavy drinking over 16 weeks. OPRM1 genotype did not significantly moderate these effects, but G-allele carriers who received naltrexone had an accelerated return to heavy drinking after medication was stopped. Smoking moderated the effects of medication on drinking, such that naltrexone was superior to placebo only among smokers. The degree of reduction in right VS activation between scans interacted with medication in predicting subsequent drinking, such that individuals with greater reduction in activation who received naltrexone, but not placebo, experienced the least heavy drinking during the following 14 weeks. These data replicate previous findings that naltrexone reduces heavy drinking and reward-related brain activation among treatment-seeking individuals with AUDs, and indicate that smoking and the magnitude of reduction in cue-elicited brain activation may predict treatment response.

Patient Perspectives Associated with Intended Duration of Buprenorphine Maintenance Therapy.

Patients with opioid use disorders frequently discontinue opioid maintenance therapy (OMT) prematurely, reducing retention and possibly limiting the efficacy of OMT. The current study is a cross-sectional survey of patients (N=69) enrolled in buprenorphine maintenance therapy (BMT). We examined patient demographics, BMT characteristics (e.g., dose, time in BMT), and patient perspectives regarding intended duration of BMT. In addition, patients' reasons for continuing or discontinuing BMT were investigated. Results revealed that the majority (82%) of participants reported wanting to continue BMT for at least 12months. Age at first drug use, time in BMT, concern about pain, and concern about relapse were all positively associated with intended duration of BMT. The following were negatively associated with intended duration of BMT: recent discussion with a treatment provider about BMT discontinuation, prior attempt to discontinue BMT, concern about withdrawal symptoms, experiencing pleasurable effects from taking buprenorphine, and perceived conflicts of BMT with life, work, or school obligations. The most common reasons for wanting to continue BMT included concerns about withdrawal symptoms, relapse, and pain. Although preliminary, the findings highlight key issues with regard to patients' perspectives of BMT. The results of this study provide information that may be useful in improving OMT programs and treatment outcomes.

Discontinuation of buprenorphine maintenance therapy: perspectives and outcomes.

Buprenorphine maintenance therapy (BMT) is increasingly the preferred opioid maintenance agent due to its reduced toxicity and availability in an office-based setting in the United States. Although BMT has been shown to be highly efficacious, it is often discontinued soon after initiation. No current systematic review has yet investigated providers' or patients' reasons for BMT discontinuation or the outcomes that follow. Hence, provider and patient perspectives associated with BMT discontinuation after a period of stable buprenorphine maintenance and the resultant outcomes were systematically reviewed with specific emphasis on pre-buprenorphine-taper parameters predictive of relapse following BMT discontinuation. Few identified studies address provider or patient perspectives associated with buprenorphine discontinuation. Within the studies reviewed providers with residency training in BMT were more likely to favor long term BMT instead of detoxification, and providers were likely to consider BMT discontinuation in the face of medication misuse. Patients often desired to remain on BMT because of fear of relapse to illicit opioid use if they were to discontinue BMT. The majority of patients who discontinued BMT did so involuntarily, often due to failure to follow strict program requirements, and 1 month following discontinuation, rates of relapse to illicit opioid use exceeded 50% in every study reviewed. Only lower buprenorphine maintenance dose, which may be a marker for attenuated addiction severity, predicted better outcomes across studies. Relaxed BMT program requirements and frequent counsel on the high probability of relapse if BMT is discontinued may improve retention in treatment and prevent the relapse to illicit opioid use that is likely to follow BMT discontinuation.

Pharmacologic treatment of alcoholism.

Progress in understanding the neuroscience of addiction has significantly advanced the development of more efficacious medications for the treatment of alcohol use disorders (AUD). While several medications have been approved by regulatory bodies around the world for the treatment of AUD, they are not universally efficacious. Recent research has yielded improved understanding of the genetics and brain circuits that underlie alcohol reward and its habitual use. This research has contributed to pharmacogenetic studies of medication response, and will ultimately lead to a more "personalized medicine" approach to AUD pharmacotherapy. This chapter summarizes work on clinically available medications (both approved by regulatory bodies and investigational) for the treatment of alcohol dependence, as well as the psychiatric disorders that are commonly comorbid with AUD. Studies that have evaluated genetic influences on medication response and those that have employed neuroimaging to probe mechanisms of medication action or response are highlighted. Finally, new targets discovered in animal models for possible pharmacologic intervention in humans are overviewed and future directions in medications development provided.

The potential utility of drinking motive questions to screen at-risk drinking in socially anxious patients.

BACKGROUND: Drinking motives are thought to be important mediators of the relationship between social anxiety and alcohol use. This project evaluates whether specific drinking motives accurately reflect alcohol dependence. If so, brief questions about drinking motives could serve as valuable alcohol screening tools with socially anxious patients. METHODS: This investigation was a secondary analysis of an existing data set of 83 subjects with social anxiety disorder and at-risk alcohol use. The relationship between Drinking Motives Questionnaire (DMQ-R-5) subscales and alcohol dependence was evaluated. RESULTS: Coping-Depression was the only subscale that contributed to the unique prediction of a diagnosis of alcohol dependence. Additionally, two items (i.e. "to cheer up when you're in a bad mood" and "to forget painful memories") predicted a diagnosis of alcohol dependence above and beyond their association with each other. CONCLUSIONS: Among patients with social anxiety, two specific questions on the DMQ-R-5 could provide a useful screen for health professionals to predict alcohol dependence. It may be fruitful to specifically target the motives of "to cheer up when you're in a bad mood" and "to forget painful memories" when providing advice during brief interventions.

Treating individuals with social anxiety disorder and at-risk drinking: phasing in a brief alcohol intervention following paroxetine.

Paroxetine alone is not sufficient to decrease alcohol use in socially anxious alcoholics seeking anxiety treatment. We tested the hypothesis that adding a brief-alcohol-intervention (BI) to paroxetine would decrease alcohol use. All subjects (N=83) had a diagnosis of social anxiety disorder, endorsed drinking to cope with anxiety, were NIAAA-defined at-risk drinkers, and were randomized to either paroxetine alone, or paroxetine plus BI. Both groups showed significant improvement in both social anxiety severity (F(5,83)=61.5, p<0.0001) and drinking to cope (e.g. F(4,79)=23, p<0.0001) and these two constructs correlated with each other (B=3.39, SE=0.696, t(71)=4.88, p<0.001). BI was not effective at decreasing alcohol use (e.g. no main effect of group, all p values >0.3). Paroxetine decreased social anxiety severity in the face of heavy drinking and decreasing the anxiety was related to a concurrent decrease in coping related drinking. BI was not effective at decreasing drinking or drinking to cope.

Severity of anxiety in mental health versus addiction treatment settings when social anxiety and substance abuse are comorbid.

There is increasing interest in the co-occurrence of social anxiety and addiction. Each investigation has a specific vantage point, e.g., the effect social anxiety has in a population with addiction or that of addiction in a population with social anxiety, which could create unique findings. Among comorbid individuals, is social anxiety more severe in people seeking treatment for anxiety, as compared to those seeking treatment for addiction? This report compares social anxiety severity between subjects in two studies--one involving socially anxious individuals (n=38) seeking treatment for addictions; the other (n=41) subjects with social anxiety and an alcohol use disorder, seeking treatment for social anxiety. Baseline severity scores on the Liebowitz Social Anxiety Scale for social anxiety were compared between the groups. No significant differences were found. For both groups, social anxiety was largely in the severe range. The results suggest that clinicians should attend to social anxiety symptom severity in patients with co-occurring social anxiety and addiction, regardless of the condition for which treatment is sought.

Client attitudes toward alcohol use self-report.

Because psychiatric illnesses and problematic alcohol use frequently co-occur and heavy alcohol use can exacerbate depression and anxiety, mental health clinicians should perform alcohol-use screenings. The aim of this study was to determine if psychiatric patients would be accepting of their mental health clinician screening them for heavy alcohol use. Using a written survey, patients rated their levels of agreement with 9 statements regarding opinions about alcohol screening by their mental-health providers. They also completed the Alcohol Use Disorders Identification Test-C (AUDIT-C), a screening instrument for heavy alcohol use. One hundred fifty-four patients were surveyed in 2 psychiatric outpatient clinics. Nearly 40% screened positively for heavy alcohol use on the AUDIT-C. Nearly 8 out of 10 psychiatric patients were in favor of being screened for alcohol use by either self-report or biomarkers, independent of AUDIT-C status and gender. Thus, mental health clinicians should not be deterred from alcohol screening by perceived negative attitudes from patients.

Training physician-scientists: a model for integrating research into psychiatric residency.

OBJECTIVE: the number of physicians engaged in research careers has declined significantly over the past two decades. Physicians with in-depth experience and formal training in research design, development, implementation, statistical analysis, and interpretation of scientific information are rare. METHODS: in response to this shortage, the Medical University of South Carolina (MUSC) launched an NIH-funded research track in 2006 to address the institutional, financial, and regulatory barriers to research training during residency. The primary aim was to incorporate a research track within a 4-year psychiatric residency program for physicians. A secondary goal was to extend recruitment into earlier phases of medical training by offering summer research fellowships to medical and undergraduate students. RESULTS: this article describes the program including core mechanisms of training, recruitment, and outcomes to date. CONCLUSIONS: the program provides a model to effectively integrate research training during residency without increasing the number of years of residency training. The training components described herein should be exportable to other psychiatric residency training programs and potentially other specialties of medicine.

Medical treatment of alcohol dependence: a systematic review.

OBJECTIVE: To summarize published data on pharmacologic treatments for alcohol dependence alone and in combination with brief psychosocial therapies that may be feasible for primary care and specialty medical settings. METHODS: We conducted electronic searches of published original research articles and reviews in MEDLINE, SCOPUS, CINAHL, Embase, and PsychINFO. In addition, hand searches of reference lists of review articles, supplemental searches of internet references and contacts with experts in the field were conducted. Randomized controlled studies published between January 1960 and August 2010 that met our inclusion/exclusion criteria were included. RESULTS: A total of 85 studies, representing 18,937 subjects, met our criteria for inclusion. The evidence base for oral naltrexone (6% more days abstinent than placebo in the largest study) and topiramate (prescribed off-label) (e.g., 26.2% more days abstinent than placebo in a recent study) is positive but modest. Acamprosate shows modest efficacy with recently abstinent patients, with European studies showing better results than U.S. ones. The evidence-base for disulfiram is equivocal. Depot naltrexone shows efficacy (25% greater reduction in rate of heavy drinking vs. placebo, in one of the largest studies) in a limited number of studies. Some studies suggest that patients do better with extensive psychosocial treatments added to medications while others show that brief support can be equally effective. CONCLUSIONS: Although treatment effects are modest, medications for alcohol dependence, in conjunction with either brief support or more extensive psychosocial therapy, can be effective in primary and specialty care medical settings.