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Over 16 million Americans meet diagnostic criteria for alcohol use disorder (AUD), but only 7.8% of them receive formal treatment each year. Safe and effective pharmacological treatments for AUD exist; however, they are rarely prescribed. Therefore, we developed and pilot tested a multifaceted implementation intervention to improve consideration and receipt of effective pharmacologic treatments for AUD, focusing on primary care settings where patients have the most frequent contact with healthcare systems. The intervention included training of local providers to serve as champions and a website for primary care providers that included educational materials, a case-finding dashboard, and contact information for local and national clinical experts. We also mailed patients educational material about treatment options. The intervention was implemented at three large facilities of the Veterans Health Administration (VHA). An interrupted time series design, analyzed with segmented logistic regression, was used to evaluate the intervention's effects. The odds of a patient with AUD receiving one of the AUD medications was increasing throughout the pre-implementation period, and the rate of change (slope) increased significantly in the implementation period. Translating these numbers into percentages, at baseline 2.9% of patients filled a prescription for an AUD medication within 30days of a primary care visit. This increased to 3.8% by the end of the pre-implementation period (increasing 0.037% per month), and increased to 5.2% by the end of the implementation period (increasing 0.142% per month). However, the intervention effect was not significant when control sites were added, suggesting that improvement may have been driven by secular trends rather than solely by this intervention. Although the intervention was feasible, it was not effective. Continued analysis of process and implementation data including qualitative interviews with key stakeholders, may elucidate the reasons this intervention was not successful and ways to strengthen its effects.

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.

The mental health needs of military service members, Veterans, and their families are a designated national priority; however, there has been little emphasis on the inclusion of Veteran-centric domains in competency-based nursing education for psychiatric–mental health nurse practitioners (PMHNPs). The current article describes the identification and application of Veteran-centric domains in an innovative pilot residency program for PMHNPs, funded by the Veterans Health Administration Office of Academic Affiliations. Fourteen Veteran-centric competency domains were developed from literature review, including knowledge, attitudes, and skill behaviors. Adoption and application of these domains in curricular components included the resident competency evaluation, baseline assessment of military experience, and evidence-based practice seminars and training. Methods of competency domain evaluation are presented, along with gaps related to the evaluation of competency skills. The delivery of mental health services reflecting these domains is consistent with the VA core values and goal of developing a positive service culture. [ Journal of Psychosocial Nursing and Mental Health Services, 54 (11), 31–36.]

Background Despite the high prevalence of alcohol use disorders (AUDs), in 2016, only 7.8% of individuals meeting diagnostic criteria received any type of AUD treatment. Developing options for treatment within primary care settings is imperative to increase treatment access. As part of a trial to implement AUD pharmacotherapy in primary care settings, this qualitative study analyzed pre-implementation provider interviews using the Consolidated Framework for Implementation Research (CFIR) to identify implementation barriers. Methods Three large Veterans Health Administration facilities participated in the implementation intervention. Local providers were trained to serve as implementation/clinical champions and received external facilitation from the project team. Primary care providers received a dashboard of patients with AUD for case identification, educational materials, and access to consultation from clinical champions. Veterans with AUD diagnoses received educational information in the mail. Prior to the start of implementation activities, 24 primary care providers (5–10 per site) participated in semi-structured interviews. Transcripts were analyzed using common coding techniques for qualitative data using the CFIR codebook Innovation/Intervention Characteristics, Outer Setting, Inner Setting, and Characteristics of Individuals domains. Number and type of barriers identified were compared to quantitative changes in AUD pharmacotherapy prescribing rates. Results Four major barriers emerged across all three sites: complexity of providing AUD pharmacotherapy in primary care, the limited compatibility of AUD treatment with existing primary care processes, providers’ limited knowledge and negative beliefs about AUD pharmacotherapy and providers’ negative attitudes toward patients with AUD. Site specific barriers included lack of relative advantage of providing AUD pharmacotherapy in primary care over current practice, complaints about the design quality and packaging of implementation intervention materials, limited priority of addressing AUD in primary care and limited available resources to implement AUD pharmacotherapy in primary care. Conclusions CFIR constructs were useful for identifying pre-implementation barriers that informed refinements to the implementation intervention. The number and type of pre-implementation barriers identified did not demonstrate a clear relationship to the degree to which sites were able to improve AUD pharmacotherapy prescribing rate. Site-level implementation process factors such as leadership support and provider turn-over likely also interacted with pre-implementation barriers to drive implementation outcomes.

In total, 75% of suicides reported to the Joint Commission as sentinel events since 1995, have occurred in psychiatric settings. Ensuring patient safety is one of the primary tasks of inpatient psychiatric units. A review of inpatient suicide-specific safety components, inclusive of incidence and risk; guidelines for evidence-based care; environmental safety; suicide risk assessment; milieu observation and monitoring; psychotherapeutic interventions; and documentation is provided. The Veterans Health Administration (VA) has been recognized as an exemplar system in suicide prevention. A VA inpatient psychiatric unit is used to illustrate the operationalization of a culture of suicide-specific safety. We conclude by describing preliminary unit outcomes and acknowledging limitations of suicide-specific inpatient care and gaps in the current inpatient practices and research on psychotherapeutic interventions, observation, and monitoring.

Candidate gene studies have yet to investigate the glutamate system, the primary excitatory neurotransmitter of the HPA-axis related to PTSD risk. We investigated 13 SNPs in the glutamate transporter gene ( SLC1A1 ) in relation to PTSD among combat-exposed veterans. Participants ( n = 418) completed a diagnostic interview and provided a blood sample for DNA isolation and genotyping. A subset of participants ( n = 391) had severity and combat exposure data available. In the primary logistic regression gender and rs10739062 were significant predictors of PTSD diagnosis (OR = 0.50; OR = 1.43). In the linear regression analysis, combat exposure was the only significant predictor ( β = 0.16) of severity. A computed genetic risk sum score was significant in relation to PTSD diagnosis (OR = 1.15) and severity scores ( β = 0.14) above and beyond the effects of combat exposure. This study provides preliminary support for the relationship of glutamate transporter polymorphisms to PTSD risk and the need for further genetic studies within this system.

Aims Functional magnetic resonance imaging research has attempted to elucidate the neurobehavioral underpinnings of cocaine dependence by evaluating differences in brain activation to cocaine and response inhibition cues between cocaine-dependent individuals and controls. This study investigated associations between task-related brain activation and cocaine use characteristics. Design Cross-sectional. Setting The Center for Biomedical Imaging at the Medical University of South Carolina, USA. Participants Fifty-one cocaine users (41 dependent). Measurements Brain activation to cocaine-cue exposure and Go No-Go tasks in six a priori selected brain regions of interest and cocaine use characteristics (i.e. cocaine dependence status, years of cocaine use, cocaine use in the past 90 days) assessed via standardized interviews. Findings Participants demonstrated elevated activation to cocaine (bilateral ventral striatum, dorsal caudate, amygdala) and response inhibition (bilateral anterior cingulate, insula, inferior frontal gyrus) cues in all hypothesized brain regions. Years of cocaine use was associated with task-related brain activation, with more years of cocaine use associated with greater activation to cocaine cues in right (F = 7.97, P = 0.01) and left (F = 5.47, P = 0.02) ventral striatum and greater activation to response inhibition cues in left insula (F = 5.10, P = 0.03) and inferior frontal gyrus (F = 4.12, P = 0.05) controlling for age, cocaine dependence status and cocaine use in the past 90 days. Conclusions Years of cocaine use may be more centrally related to cocaine cue and response inhibition brain activation than cocaine dependence diagnosis or amount of recent use.

The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas.This pilot study tested varenicline's effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals.Thirty-five such individuals (mean age = 30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC).Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas.These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption.

There has been increasing interest in using video telehealth to deliver evidence-based psychotherapies (EBPs). Telehealth may have numerous advantages over standard in-person care, including decreasing patients’ and providers’ costs and increasing system coverage area. However, little is known regarding the effectiveness of EBPs via video telehealth. This review had two goals, including a review of the existing literature and ongoing research on using video telehealth technologies to deliver EBPs as well as an informal survey of telehealth experts to discuss the special considerations and challenges present in adapting practices to video telehealth. Together, findings suggest that telehealth practices could represent an important component of the future of psychotherapy and clinical practice, especially in dissemination and implementation of EBPs in traditionally underserved areas and populations.

Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism.This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy.Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task.There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking.These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.

Posttraumatic stress disorder (PTSD) is associated with functional impairment, co-occurring diagnoses, and increased health care utilization. Associated high demand for health care services is an important contributor to the large public-health cost of PTSD. Treatments incorporating exposure therapy are efficacious in ameliorating or eliminating PTSD symptoms. Accordingly, the Veterans Health Administration has made significant investments toward nationwide dissemination of a manualized exposure therapy protocol, prolonged exposure (PE). PE is effective with veterans; however, the relationship between PE and mental health service utilization is unknown. The current study investigates PE as it relates to actual tracked mental health service utilization in an urban VA medical center. A sample of 60 veterans with a diagnosis of PTSD was used to examine mental health service utilization in the 12-months prior to and 12-months after being offered PE. Hierarchical Linear Models and traditional repeated-measures ANOVA were used to estimate R²- and d-type effect sizes for service utilization. Associated estimated cost saving are reported. PE was associated with large reductions in symptoms and diagnosis remission. Treatment was also associated with statistically significant, large reductions in mental health service utilization for veterans who completed treatment. Findings suggest that expanding access to PE can increase access to mental health services in general by decreasing ongoing demand for specialty care clinical services.

Background: Neuroimaging of drug-associated cue presentations has aided in understanding the neurobiological substrates of craving and relapse for cocaine, alcohol, and nicotine. However, imaging of cue-reactivity in methamphetamine addiction has been much less studied. Method: Nine caucasian male methamphetamine-dependent subjects and nine healthy controls were scanned in a Phillips 3.0T MRI scan when they viewed a randomized presentation of visual cues of methamphetamine, neutral objects, and rest conditions. Functional Imaging data were analyzed with Statistical Parametric Mapping software 5 (SPM 5) Results: Methamphetamine subjects had significant brain activation in the ventral striatum and medial frontal cortex in comparison to meth pictures and neutral pictures in healthy controls (p

Variation at a single nucleotide polymorphism in the μ-opioid receptor gene (OPRM1), A118G (Asn40Asp), may moderate naltrexone (NTX) effects in alcohol dependence. Both NTX and A118G variation have also been reported to affect alcohol cue-elicited brain activation. This study investigated whether sub-acute NTX treatment and A118G genotype interacted in their effects on cue-elicited activation of the ventral striatum (VS), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Secondarily, variation at a variable number tandem repeat polymorphism in the dopamine transporter gene (DAT1/SLC6A3), which has been associated with increased reward-related activation in VS, was analyzed as a moderator of medication and A118G effects. Seventy-four non-treatment-seeking alcohol-dependent individuals, half preselected to carry at least one copy of the A118G G (Asp) allele, were randomized to NTX (50 mg) or placebo for 7 days, and performed an fMRI alcohol cue reactivity task on day 6. Region-of-interest analyses indicated no main effects of medication or A118G genotype. However, these factors interacted in their effects on OFC activation, such that, among NTX-treated individuals, G-allele carriers had less activation than A-allele homozygotes. DAT1 variation also moderated medication/A118G effects. There was a three-way interaction between medication and A118G and DAT1 genotypes on VS activation, such that, among G-allele carriers who received NTX, DAT1 10-repeat-allele (10R) homozygotes had less activation than 9-repeat-allele (9R) carriers. Further, 10R homozygotes who received NTX had less mPFC activation than 9R carriers. Polymorphic variation in OPRM1 and DAT1 should be considered in future studies of NTX, particularly regarding its effects on reward processing.

Divalproex, a GABA agonist, may be a useful agent in the treatment of tobacco dependence. Cue reactivity assessment paradigms are ideally suited to explore basic mechanisms underlying the pharmacological effects of medications that purport to have efficacy for smoking cessation. Our primary goal in the current study was to examine the effects of divalproex on in-treatment reactivity to smoking-relevant and affective cues, and to determine if these reactions were predictive of posttreatment smoking behavior. There were 120 nicotine dependent smokers enrolled in an 8-week double-blind clinical trial and randomly assigned to either divalproex or placebo conditions. Of these, 72 smokers (60% female) who achieved a minimal level of abstinence underwent an in-treatment cue reactivity assessment. Contrary to expectations, divalproex was associated with greater craving and arousal during smoking cue presentation. Divalproex also inhibited cardiovascular response to pleasant cues. Although no significant differences in cessation-related outcomes between divalproex- and placebo-treated participants were observed, cue-elicited craving to smoke predicted end-of-treatment and posttreatment smoking rates. These findings suggest that in-treatment cue reactivity assessment may proactively and dynamically inform ongoing treatment as well as provide a tool for screening potential medications for smoking cessation.

A comprehensive understanding of the neurobiology of alcohol cue reactivity is critical in identifying the neuropathology of alcohol use disorders (AUD) and developing treatments that may attenuate alcohol craving and reduce relapse risk. Functional neuroimaging studies have identified many brain areas in which alcohol cues elicit activation. However, extant studies have included relatively small numbers of cases, with AUD of varying severity, and have employed many different cue paradigms. We used activation likelihood estimation, a quantitative, coordinate-based meta-analytic method, to analyze the brain areas activated by alcohol-related cues across studies, and to examine whether these areas were differentially activated between cases and controls. Secondarily, we reviewed correlations between behavioral measures and cue-elicited activation, as well as treatment effects on such activation. Data analyzed were from 28 studies of 679 cases and 174 controls. Among cases, alcohol cues elicited robust activation of limbic and prefrontal regions, including ventral striatum, anterior cingulate and ventromedial prefrontal cortex. As compared to controls, cases demonstrated greater activation of parietal and temporal regions, including posterior cingulate, precuneus and superior temporal gyrus. Cue-elicited activation of ventral striatum was most frequently correlated with behavioral measures and most frequently reduced by treatment, but these results were often derived from region-of-interest analyses that interrogated only limbic regions. These findings support long-standing theories of mesolimbic involvement in alcohol cue processing, but suggest that cue-elicited activation of other brain areas may more clearly differentiate cases from controls. Prevention and treatment for AUD should consider interventions that may reduce cue-elicited activation of these areas.

Background Naltrexone is moderately effective for the treatment of alcohol dependence, but there is great individual variability. The opioid receptor (OPRM1) single nucleotide polymorphism (SNP) asn40asp has been shown to alter alcohol and naltrexone response in animals and humans. In addition, the brain opioid and dopamine systems interact and might underlie drinking and craving. This study investigated the effects of the OPRM1 SNP and dopamine transporter (DAT) variable number of tandem repeat (VNTR) genetic differences on drinking, alcohol effects, and naltrexone response under controlled conditions in nontreatment-seeking alcoholics. Methods Two hundred and sixty-five nontreatment-seeking individuals with alcohol dependence were genotyped a priori for the OPRM1 asn40asp SNP and post hoc for DAT (SLC6A3) 9 and 10 VNTRs. Asp40 carriers (n = 43) and matched asn40 homozygotes (n = 40) were randomized to naltrexone or placebo for 7 days before receiving a priming drink and limited-access alcohol consumption in a bar-lab setting. Effects of genotypes on natural drinking as well as drinking, alcohol effects, and response to naltrexone in the bar-lab setting were examined by genotype. Results There were no significant main effects of naltrexone or OPRM1 genotype, or any medication by OPRM1 interaction, on drinking variables. However, in individuals who had at least one DAT 9 VNTR, and who were also OPRM1 asn40 homozygotes, naltrexone reduced drinks/d consumed under natural conditions (p = 0.006), but not in the bar-lab. OPRM1 asn40 homozygotes (p = 0.028) and DAT 9 VNTR carriers (p = 0.032) had more stimulation to alcohol after the priming drink. Conclusions This study does not support a salient role for the OPRM1 asp40 alone in predicting drinking or naltrexone effects. However, although exploratory and in need of replication, it introduces the possibility that epistasis between the OPRM1 gene and DAT gene might need to be taken into account when examining differential genetic response to alcohol or medication treatment, especially in early-stage alcoholics.

Motivation to change is believed to be a key factor in therapeutic success in substance use disorders; however, the neurobiological mechanisms through which motivation to change impacts decreased substance use remain unclear. Existing research is conflicting, with some investigations supporting decreased and others reporting increased frontal activation to drug cues in individuals seeking treatment for substance use disorders. The present study investigated the relationship between motivation to change cocaine use and cue-elicited brain activity in cocaine-dependent individuals using two conceptualizations of 'motivation to change': (1) current treatment status (i.e. currently receiving versus not receiving outpatient treatment for cocaine dependence) and (2) self-reported motivation to change substance use, using the Stages of Change Readiness and Treatment Eagerness Scale. Thirty-eight cocaine-dependent individuals (14 currently in treatment) completed a diagnostic assessment and an fMRI cocaine cue-reactivity task. Whole-brain analyses demonstrated that both treatment-seeking and motivated participants had lower activation to cocaine cues in a wide variety of brain regions in the frontal, occipital, temporal and cingulate cortices relative to non-treatment-seeking and less motivated participants. Future research is needed to explain the mechanism by which treatment and/or motivation impacts neural cue reactivity, as such work could potentially aid in the development of more effective therapeutic techniques for substance-dependent patients.

OBJECTIVE To evaluate exercise as a treatment for stimulant use disorders. METHODS The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks. The primary outcome of percent stimulant abstinent days during study weeks 4 to 12 was estimated using a novel algorithm adjustment incorporating self-reported Timeline Followback (TLFB) stimulant use and urine drug screen (UDS) data. RESULTS Mean percent of abstinent days based on TLFB was 90.8% (SD = 16.4%) for Exercise and 91.6% (SD = 14.7%) for Health Education participants. Percent of abstinent days using the eliminate contradiction (ELCON) algorithm was 75.6% (SD = 27.4%) for Exercise and 77.3% (SD = 25.1%) for Health Education. The primary intent-to-treat analysis, using a mixed model controlling for site and the ELCON algorithm, produced no treatment effect (P = .60). In post hoc analyses controlling for treatment adherence and baseline stimulant use, Exercise participants had a 4.8% higher abstinence rate (78.7%) compared to Health Education participants (73.9%) (P = .03, number needed to treat = 7.2). CONCLUSIONS The primary analysis indicated no significant difference between exercise and health education. Adjustment for intervention adherence showed modestly but significantly higher percent of abstinent days in the exercise group, suggesting that exercise may improve outcomes for stimulant users who have better adherence to an exercise dose. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01141608.

Background Only 7.8 % of individuals meeting diagnostic criteria for alcohol use disorder (AUD) receive treatment in a given year. Most individuals with AUDs are identified in primary care (PC) settings and referred to substance use disorders (SUD) clinics; however, only a minority of those referred attend treatment services. Safe and effective pharmacological treatments for AUD exist, but they are rarely prescribed by PC providers. The objective of this study is to refine, implement, and evaluate an intervention to integrate pharmacological AUD treatment options into PC settings. This paper provides a detailed description of the intervention design and the evaluation components. Methods/design Three large Veterans Health Administration (VHA) facilities are participating in the intervention. The intervention targets stakeholder groups with tailored strategies based on implementation theory and prior research identifying barriers to implementation of AUD pharmacotherapy. Local SUD providers and primary care mental health integration (PCMHI) providers are trained to serve as local implementation/clinical champions and receive external facilitation. PC providers receive access to consultation from local and national clinical champions, educational materials, and a dashboard of patients with AUD on their caseloads for case identification. Veterans with AUD diagnoses receive educational information in the mail just prior to a scheduled PC visit. Effectiveness of the intervention will be evaluated through an interrupted time series with matched controls to monitor change in facility level AUD pharmacotherapy prescribing rates. Following Stetler’s four-phase formative evaluation (FE) strategy, FE methods include (1) developmental FE (pre-implementation interviews with champions, PC providers, and Veterans), (2) implementation-focused FE (tracking attendance at facilitation meetings, academic detailing efforts by local champions, and patient dashboard utilization), (3) progress-focused FE (tracking rates of AUD pharmacotherapy prescribing and rates of referral to PCMHI and SUD specialty care), and (4) interpretive FE (post-implementation interviews with champions and PC providers). Analysis of FE data will be guided by the Consolidated Framework for Implementation Research (CFIR). Discussion If demonstrated to be successful, this implementation strategy will provide a replicable, feasible, and relative low-cost method for integrating AUD treatment services into PC settings, thereby increasing access to AUD treatment.

Craving is a significant factor which can lead to relapse during smoking quit attempts. Attempts to resist urges to smoke during cue-elicited craving have been shown to activate regions in the brain associated with decision-making, anxiety regulation and visual processing. In this study, 32 treatment-seeking, nicotine-dependent smokers viewed blocks of smoking and neutral cues alternating with rest periods during magnetic resonance imaging scanning in a 3T Siemens scanner (Siemens AG, Erlangen, Bavaria, Germany). While viewing cues or control images, participants were instructed either to ‘allow yourself to crave’ or ‘resist craving.’ Data were analyzed with FSL 4.1.5, focused on the smoking cues versus neutral cues contrast, using cluster thresholding (Z > 2.3 and corrected cluster threshold of P = 0.05) at the individual and group levels. During the Crave condition, activation was seen on the left anterior cingulated cortex (LACC), medial prefrontal cortex, left middle cingulate gyrus, bilateral posterior cingulated gyrus and bilateral precuneus, areas associated with attention, decision-making and episodic memory. The LACC and areas of the prefrontal cortex associated with higher executive functioning were activated during the Resist condition. No clear distinctions between group crave and resist analyses as a whole were seen without taking into account specific strategies used to resist the urge to smoke, supporting the idea that craving is associated with some degree of resisting the urge to smoke, and trying to resist is almost always accompanied by some degree of craving. Different strategies for resisting, such as distraction, activated different regions. Understanding the underlying neurobiology of resisting craving to smoke may identify new foci for treatments.

Background: Among some alcohol-dependent individuals, early alcohol abstinence is marked by alcohol withdrawal (AW), a phenomenon mediated by GABA and glutamate signaling. We previously reported that a combination of 2 medications that affect GABA and glutamate tone, gabapentin and flumazenil, more effectively reduced drinking among individuals with higher pretreatment AW (Anton et al., 2009). This study evaluated whether this finding is related to changes in neurocognitive performance, which is also affected by cortical GABA and glutamate tone. Methods: Neurocognitive performance was assessed at baseline and twice during the first week of treatment among 60 alcohol-dependent participants in the previously published clinical trial. Results: AW was associated with poorer baseline performance on 4 of 8 measures, and individuals with higher baseline AW who received the gabapentin and flumazenil combination demonstrated greater improvement on a measure of response inhibition than those with lower AW or those who received a combination of placebos. Improvement in response inhibition during the first week and medication group interacted in their effect on subsequent drinking, such that improvement predicted greater abstinence only among individuals who received gabapentin and flumazenil. Improvement on other neurocognitive measures was neither differentially impacted by medication or baseline AW nor related to subsequent drinking. Conclusions: Taken together, these data suggest that acute AW accounts for a small proportion of variance in neurocognitive performance, that gabapentin and flumazenil slightly improve response inhibition during early abstinence, and that such improvement may somewhat reduce later drinking. However, these medications may not affect other neurocognitive domains.

In functional magnetic resonance imaging (fMRI) studies of alcohol-dependent individuals, alcohol cues elicit activation of the ventral and dorsal aspects of the striatum (VS and DS), which are believed to underlie aspects of reward learning critical to the initiation and maintenance of alcohol dependence. Cue-elicited striatal activation may represent a biological substrate through which treatment efficacy may be measured. However, to be useful for this purpose, VS or DS activation must first demonstrate stability across time. Using hierarchical linear modeling (HLM), this study tested the stability of cue-elicited activation in anatomically and functionally defined regions of interest in bilateral VS and DS. Nine non-treatment-seeking alcohol-dependent participants twice completed an alcohol cue reactivity task during two fMRI scans separated by 14 days. HLM analyses demonstrated that, across all participants, alcohol cues elicited significant activation in each of the regions of interest. At the group level, these activations attenuated slightly between scans, but session-wise differences were not significant. Within-participants stability was best in the anatomically defined right VS and DS and in a functionally defined region that encompassed right caudate and putamen (intraclass correlation coefficients of .75, .81, and .76, respectively). Thus, within this small sample, alcohol cue-elicited fMRI activation had good reliability in the right striatum, though a larger sample is necessary to ensure generalizability and further evaluate stability. This study also demonstrates the utility of HLM analytic techniques for serial fMRI studies, in which separating within-participants variance (individual changes in activation) from between-participants factors (time or treatment) is critical.

The Veteran's Health Administration (VHA) has launched a large-scale initiative to promote prolonged exposure (PE) therapy, an evidence-based treatment for PTSD. While existing randomized controlled trials (RCTs) unambiguously support the efficacy of PE in civilian and some military populations, there is a need to better understand the course of treatment for combat Veterans of the current wars receiving PE in normative mental healthcare settings. The current study investigates 65 Veterans receiving care at an urban VA medical center. All Veterans were diagnosed with PTSD via a structured interview and treated with PE. Measures of PTSD and depression were collected pre- and post-treatment and every two sessions during treatment. Dependent means t-tests were used to estimate pre- and post-treatment d-type effect sizes. Additionally, hierarchical linear models (HLM) were used to investigate treatment effects over time, relationships between patient characteristics and outcomes, and to provide estimates of R(2)-type effect sizes. Results indicate that PE in regular VA mental healthcare contexts can be as effective as when implemented in carefully conducted RCTs.

Co-morbid bipolar and alcohol use disorders are common, difficult to properly diagnose, and associated with poor outcome. The present article concisely reviews the diagnosis, epidemiology, consequences, and neurobiological similarities among individuals with dual diagnoses and reviews the pharmacological and psychosocial treatment of bipolar and alcohol use disorders both alone and in combination. Evidence for the efficacy of treatments for individuals with dual diagnoses (i.e., divalproex, atypical antipsychotics, naltrexone, cognitive-behavioral therapy, and integrated group therapy) is discussed, and areas for future treatment development and evaluation are identified.

Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial.One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) ratingsor =10 were randomized to double-blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels.CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin-treated participants (p = 0.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam-treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam.Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.

Previous work has shown that multiple medication-treated alcohol detoxifications are associated with poorer treatment outcomes during subsequent detoxifications. Little is known about the impact of nonmedicated attempts to stop drinking outside the realm of these medically supervised detoxifications on acute detoxification outcomes. This study included 58 subjects enrolled in an outpatient detoxification study. Subjects were asked why and how often they quit alcohol for 3 days or longer during their drinking lifetime using concepts derived from the Cognitive Lifetime Drinking History. The effect of previous attempts at abstinence (both medicated and nonmedicated) on time to relapse during an index detoxification was examined. After the index detoxification, older individuals relapsed later than younger individuals and the number of previous medicated detoxifications rather than total lifetime quit attempts per se was related to quicker relapse. Contrary to expectation, those who reported fewer previous nonmedicated quit attempts tended to relapse sooner than those who reported more past quit attempts. This study supports and extends previous work that suggests that the number of previous medicated detoxifications, rather than the total number of past attempts at abstinence, predicts higher and sooner risk for early relapse drinking during outpatient alcohol detoxification.

Aims: Pregabalin has been shown to possess anticonvulsant, analgesic, and anxiolytic properties in a variety of testing situations. This study was designed to evaluate the ability of pregabalin to exert its anticonvulsant effects against behavioral and electrographic measures of CNS hyperexcitability associated with alcohol withdrawal in a mouse model of ethanol dependence. Methods: Adult mice were chronically exposed to ethanol and, upon withdrawal, were tested for behavioral signs of seizure activity (handling-induced convulsions) or abnormalities in spontaneous EEG activity recorded from cortical and subcortical sites. Results: Pregabalin (50-200 mg/kg) administered 1 and 4 h into withdrawal dose dependently reduced severity of handling-induced convulsions in comparison to vehicle-treated mice. Similarly, pregabalin reduced the frequency in which EEG activity was interrupted by trains of high-voltage synchronous activity in a dose-related fashion. Finally, pregabalin treatment of repeated withdrawals was effective in blocking the development of withdrawal sensitization observed in vehicle-treated mice.Conclusions: Collectively, these results suggest that pregabalin may be an effective therapeutic agent for medical management of alcohol detoxification.

Acamprosate, a medication that has been used in Europe for years, is the newest drug to be approved by the US Federal Drug Administration for the treatment of alcohol dependence. It has been shown to assist in the maintenance of abstinence in recently detoxified alcohol-dependent individuals. The following review delineates the proposed mechanism of action and pharmacokinetics of the drug. Findings of clinical trials are outlined and topics such as cost effectiveness, comparison with other medications used for the treatment of alcohol dependences as well as combination pharmacotherapy are discussed. In combination with psychosocial treatment, acamprosate is a promising tool for the maintenance of abstinence in alcohol-dependent patients after alcohol withdrawal. This review also illustrates the continued need to search for more effective treatments, as the overall effectiveness of our currently available pharmacotherapies remains limited in the long-term maintenance of recovery from alcohol dependence.

Substance abuse comorbidity is common in anxiety disorders. This article reviews the co-occurrence and etiopathological significance of comorbid substance abuse in anxiety disorders.

The aim of the current study was to evaluate the role of beliefs about alcohol use and craving on predicting relapse as stated in Beck's cognitive theory of alcoholism in detoxified alcohol-dependent patients.Seventy male participants who were alcohol dependent according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), and who were admitted to an inpatient unit for alcohol detoxification were studied at baseline and at 6 months follow-up. Participants were administered the Structured Clinical Interviews for DSM-IV axis I and DSM-III-R axis II Disorders (SCID-I and SCID-II, respectively), the Beck Anxiety Inventory and the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). Beliefs about alcohol use were assessed with the Beliefs About Substance Use Inventory and the Craving Beliefs Questionnaire (CBQ).The relapse rate of the study group was 84.1% (58 patients). The age of onset of alcohol dependence and age at first hospitalization were lower in patients who relapsed. The severity of physical dependence and presence of comorbid antisocial personality disorder were higher in the relapse group. In addition, patients who relapsed had higher scores in the CBQ. According to logistic regression analysis, craving beliefs and the degree of physical dependence were predictors of relapse in alcoholic patients.Our findings suggest that beliefs about craving and the severity of physical dependence may play an important role in relapse of male alcoholic patients. These factors could have a direct clinical application for predicting relapse to drinking in male alcohol-dependent patients.

Videoconferencing at a bandwidth of 384 kbit/s was used in open sessions for subjects with alcohol use disorders (AUD). Study participants received eight sessions of group therapy over a four-week period from an accredited addictions counsellor. Outcome assessment included self-report measures, a qualitative interview and a chart review. Of the 18 subjects who started the study, 14 attended at least four sessions of therapy, completed self-report assessments and the thematic interview. The participants reported high levels of satisfaction with telepsychiatry, found the intervention to be highly credible, had good session attendance and attrition comparable to that expected with conventional same-room treatment. In all, 82% of subjects reported that they would recommend the service to a friend or family member. The results demonstrate the feasibility of using videoconferencing for service delivery to adults with AUD, and encourage the future performance of randomized controlled trials.

Although naltrexone has been shown to be effective in the treatment of alcohol dependence, less is known about its efficacy when combined with different behavioral therapies. Previous work has suggested that naltrexone works best when combined with weekly cognitive behavioral therapy (CBT). This study examined the efficacy of naltrexone when combined with CBT or a motivational enhancement therapy involving less patient contact. Outpatient alcoholics (N = 160) were randomly assigned to either naltrexone (50 mg/d) or placebo and either CBT (12 sessions) or motivational enhancement therapy (4 sessions), in a 4-cell design, and treated over a 12-week period. Subjects were evaluated periodically for alcohol consumption, craving, and biologic markers of drinking (carbohydrate-deficient transferrin and gamma-glutamyltransferase). There was high retention and adherence to therapy and medication in the trial with no significant difference across the treatment groups. Naltrexone, independent of therapy assignment, increased the time to first relapse. However, the CBT-naltrexone group did better than the other groups on a variety of outcome measures. Fewer CBT-naltrexone-treated subjects relapsed, and those that did had both fewer, and more time between, subsequent relapses. This randomized controlled trial is consistent with previous reports about the utility of combining naltrexone with CBT. Despite being more efficient to administer, the combination of motivational enhancement therapy and naltrexone is less effective than CBT and naltrexone. Because CBT and naltrexone share common mechanisms of action, such as craving reduction and relapse prevention, these therapies are likely to be well suited to use in combination.

This study tested the hypothesis that patients with comorbid bipolar and substance use disorders use health services to a greater extent than patients with either bipolar or substance use disorder alone.A retrospective chart review was conducted among patients who used health services at the Ralph H. Johnson Department of Veterans Affairs medical center in Charleston, South Carolina, and had bipolar disorder alone, substance use disorder alone, and comorbid bipolar and substance use disorders. Patients with a psychiatric admission between 1999 and 2003 were included in the study. Information was collected on the use of health services one year before and including the index admission.The records of 106 eligible patients were examined for this study: 18 had bipolar disorder alone, 39 had substance use disorder alone, and 49 had both bipolar and substance use disorders. Compared with the other two groups, the group with comorbid bipolar and substance use disorders was significantly more likely to be suicidal. Compared with the group with bipolar disorder alone, the group with comorbid disorders had significantly fewer outpatient psychiatric visits and tended to have shorter psychiatric hospitalizations. Among patients with an alcohol use disorder, those who also had bipolar disorder were significantly less likely than those with an alcohol use disorder alone to have had an alcohol-related seizure. Patients with comorbid bipolar and substance use disorders were significantly less likely than those with substance use disorder alone to be referred for intensive substance abuse treatment, even though both groups were equally likely to enter and complete treatment when they were referred.Despite significant functional impairment among patients with comorbid bipolar and substance use disorders, they had significantly fewer psychiatric outpatient visits than those with bipolar disorder alone and were referred for intensive substance abuse treatment significantly less often than those with substance use disorder alone.

There have been many recent developments in the pharmacological management of alcohol withdrawal and alcohol dependence. Although previous treatments had included benzodiazepines as their mainstay, the use of these agents in the alcoholic population is problematic. Benzodiazepines are themselves addictive and they may increase the risk of alcohol relapse. Non-benzodiazepine anticonvulsants such as carbamazepine, valproic acid, gabapentin, vigabatrin and topiramate have been shown to be excellent treatments of both alcohol withdrawal and the prevention of alcohol relapse. Although none of these agents have yet been approved by the FDA, there is growing evidence in the literature to support their use.

This article highlights the proceedings of a symposium presented at the 27th Annual Scientific Meeting of the Research Society on Alcoholism in Vancouver, British Columbia, Canada, June 29, 2004. The organizers and co-chairs were Bankole A. Johnson, MD, PhD, and Robert M. Swift, MD, PhD. The presentations included (1) Introduction, by Bankole A. Johnson; (2) Safety, Tolerability, and Efficacy of γ-Hydroxybutyric Acid and Baclofen in the Treatment of Alcohol Addiction, by Giovanni Addolorato; (3) Safety of Gabapentin in Treating Alcoholism, by Hugh Myrick; (4) New Data on the Safety and Effectiveness of Topiramate in the Treatment of Alcohol Dependence, by Bankole A. Johnson; (5) Evaluating the Risk of Benzodiazepine Prescription to Alcohol-Dependent Individuals, by Domenic A. Ciraulo; and (6) Safety and Efficacy of GABAergic Agents in Treating Alcoholics: Discussion, by Robert M. Swift.

There is growing interest in the co-occurrence of mood and substance use disorders. It is clear that co-occurrence of these disorders is common and has an impact on prognosis and course of both disorders. The diagnostic issues at the interface of substance or alcohol use disorders and affective illnesses are particularly difficult because of the substantial symptom overlap between substance intoxication and withdrawal and symptoms of affective disorders. Over the past few years, advances have been made in the treatment of co-occurring disorders. Further investigation of specifically tailored treatments for patients with co-occurring substance use and other mood disorders is underway. Because many advances have been made in pharmacotherapy of mood disorders in the past 10 years, this progress will impact individuals with co-occurring disorders, because newer agents with less toxicity and fewer adverse effects and interactions with substances of abuse will be evaluated for treating the comorbid condition. Specific considerations in choosing a pharmacologic agent for use in patients with substance use disorders include safety, toxicity, and abuse liability. Although there are few studies specifically targeting pharmacotherapy for co-occurring disorders, those that have been conducted indicate that similar pharmacotherapeutic agents work for mood disorders with or without substance use disorders. In conclusion, although the co-occurrence of substance abuse and mood disorders is an important area in which recent developments provide cause for considerable optimism, much work remains to be done.

BACKGROUND The resting motor threshold (rMT) is the basic unit of transcranial magnetic stimulation (TMS) dosing. Traditional methods of determining rMT involve finding a threshold of either visible movement or electromyography (EMG) motor-evoked potentials, commonly approached from above and below and then averaged. This time-consuming method typically uses many TMS pulses. Mathematical programs can efficiently determine a threshold by calculating the next intensity needed based on the prior results. Within our group of experienced TMS researchers, we sought to perform an illustrative study to compare one of these programs, the Maximum-Likelihood Strategy using Parameter Estimation by Sequential Testing (MLS-PEST) approach, to a modification of the traditional International Federation of Clinical Neurophysiology (IFCN) method for determining rMT in terms of the time and pulses required and the rMT value. METHODS One subject participated in the study. Five researchers determined the same subject's rMT on 4 separate days-twice using EMG and twice using visible movement. On each visit, researchers used both the MLS-PEST and the IFCN methods, in alternating order. RESULTS The MLS-PEST approach was significantly faster and used fewer pulses to estimate rMT. For EMG-determined rMT, MLS-PEST and IFCN derived similar rMT, whereas for visible movement MLS-PEST rMT was higher than for IFCN. CONCLUSIONS The MLS-PEST algorithm is a promising alternative to traditional, time-consuming methods for determining rMT. Because the EMG-PEST method is totally automated, it may prove useful in studies using rMT as a quickly changing variable, as well as in large-scale clinical trials. Further work with PEST is warranted.

Modafinil is an agent that is frequently used in the treatment of narcolepsy. More recently it has been used in the treatment of a variety of psychiatric, neurological, and medical illnesses. Due to its ability to improve wakefulness, modafinil has been viewed as a stimulant. Based on the potential for modafinil to become widely used in a variety of syndromes and settings, evidence from preclinical in vitro and in vivo studies, human laboratory studies, and post-marketing experiences examining the potential abuse liability of modafinil were reviewed. Initial evidence suggests that modafinil has limited potential for large-scale abuse.

Using fMRI, our group previously found that after a sip of alcohol and exposure to alcohol beverage pictures, alcoholics compared to social drinkers had increased differential brain activity in the prefrontal cortex and anterior thalamus. This study extends this earlier work with several improvements including imaging the entire brain (rather than the anterior half previously) and recording craving, while the subjects viewed images within the scanner. In a Philips 1.5 T MRI scanner, 10 nontreatment-seeking alcoholics and 10 age-matched healthy social drinkers were given a sip of alcohol before viewing a 12 min randomized presentation of pictures of alcoholic beverages, nonalcoholic beverages, and two different visual control tasks. During picture presentation, changes in regional brain activity were measured in 15 transverse T2(*)-weighted blood oxygen level dependent slices. Subjects rated their urge to drink after each picture sequence. After a sip of alcohol, while viewing alcohol cues compared to viewing other beverage cues, the alcoholics, but not social drinkers, reported higher craving ratings and had increased activity in the prefrontal cortex and anterior limbic regions. Brain activity in the left nucleus accumbens, anterior cingulate, and left orbitofrontal cortex significantly correlated with subjective craving ratings in alcohol subjects but not in control subjects. This study suggests, as did our earlier study, that alcoholics and not social drinkers, when exposed to alcohol cues, have increased brain activity in areas that reportedly subserve craving for other addictive substances.

Background: An understanding of the neurophysiological mechanisms underlying alcohol craving is important in the effective treatment of alcohol dependence. The aim of this study was to examine the utility of the electroencephalogram (EEG) to measure the changes in electrical brain activity of alcoholics when exposed to alcohol-specific cues. Methods: Fifteen adult alcoholic subjects (four women) with a mean age of 35 (SD = 4.5) and 10 healthy social drinking controls (three women) with a mean age of 34 (SD = 5.6) were recruited. Subjects were serially rated for alcohol craving after presentations of pictures of control nonalcoholic and alcohol beverages. After the picture presentation, the EEG was recorded (16,384 data points for each epoch) with eyes closed. The dimensional complexity (D 2 ) was estimated as a measure of complexity of the EEG. Results: Alcoholic subjects exhibited a significant increase in the D 2 values of the EEG in frontal (F 3 , F 4 ), right posterior temporal (T 6 ), and occipital (O 1 , O 2 ) regions after viewing alcohol cues compared with viewing other beverage cues. These results indicate that more complex (or higher) cortical activity is induced over specific brain regions of alcoholic subjects by alcohol-specific cues. Changes in subscale of alcohol craving between nonalcoholic and alcohol pictures were correlated with changes in D 2 values in the left frontal (F 3 ) region in alcoholic subjects. Conclusions: These findings suggest that, when subjects are exposed to alcohol cues, changes in the EEG complexity are induced in frontal, right posterior temporal, and occipital areas, which may be key brain structures for alcohol craving. In addition, nonlinear measures like the D 2 are useful in evaluating alcohol cue-induced brain activity from the EEG.

The co-occurrence of substance abuse and mood and anxiety disorders is common and has important treatment implications. Recent investigations of pharmacotherapeutic and psychotherapeutic strategies specifically targeting individuals with comorbidity provide cause for optimism, but much work remains to be done. Purpose of review This review will provide an update on the diagnoses treatment of co-occurring mood/anxiety and substance use disorders. Interest in co-occurring disorders is growing because of the prevalence and negative impact of comorbidity on course, treatment outcomes and prognoses of both disorders. Recent findings There have been a number of recent studies exploring psychotherapeutic and pharmacotherapeutic treatment of co-occurring disorders. In particular, serotonin reuptake inhibitors and/or buspirone have demonstrated efficacy in decreasing consumption and improving psychiatric symptons in individuals with depression, social phobia and generalized anxiety disorder. There have been promising pilot studies exploring manualguided psychotherapeutic interventions specifically targeting individuals with co-occurring substance use and post-traumatic stress disorder, depression and bipolar disorder.

Anticonvulsant agents show promise in the treatment of the acute symptoms of alcohol withdrawal and may also treat some symptoms associated with the protracted abstinence syndrome. Impulsivity, hostility and irritability are common characteristics of alcohol-dependent individuals, and there is some evidence that anticonvulsant agents decrease these traits in individuals with a number of different psychiatric disorders. This pilot study is a 12-week, double-blind, placebo-controlled trial of an anticonvulsant agent, divalproex (DVPX), in alcohol-dependent individuals. Alcohol use (Timeline Follow Back), impulsivity (Barratt Impulsivity Scale), irritability and aggression (Buss-Durkee Hostility Index; and Anger, Irritability, Aggression Scale) were measured at baseline and throughout the 12-week treatment period. Drinking decreased significantly in both the placebo and the DVPX-treated groups. In the DVPX group, a significantly smaller percentage of individuals relapsed to heavy drinking, but there were no significant differences in other alcohol-related outcomes. There were significantly greater decreases in irritability in the DVPX-treated group and a trend towards greater decreases on measures of lability and verbal assault. There were no significant between-group differences on measures of impulsivity. While DVPX did not have a robust effect on alcohol-related outcomes, it did have modest impact on a measure of irritability. This is consistent with the findings of other investigators exploring the use of DVPX in schizophrenia, personality disorder and a number of other psychiatric disorders.

A double-blind, randomized controlled trial of patients (n = 136) meeting DSM-IV criteria for alcohol withdrawal and stratified based on detoxification history were treated with carbamazepine or lorazepam for 5 days on a fixed dose tapering schedule. Mood symptoms improved for all subjects regardless of medication or detoxification history. There was a significant main effect favoring carbamazepine in reducing anxiety (p = 0.0007). Anxiety was highest in those individuals who had multiple previous detoxifications (p = 0.02). Visual analog measures of sleep quality indicated a statistically significant main effect of medication on sleep that again favored carbamazepine (p = 0.0186). Visual analog rating of perceived ability to return to work was decreased in individuals who had multiple previous detoxifications (p = 0.025). In this study of outpatients with mild to moderate alcohol withdrawal, carbamazepine was superior to lorazepam in reducing anxiety and improving sleep.