Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

Neuroimaging studies of cannabidiol and potential neurobiological mechanisms relevant for alcohol use disorders: a systematic review.

The underlying neurobiological mechanisms of cannabidiol's (CBD) management of alcohol use disorder (AUD) remains elusive.Aim We conducted a systematic review of neuroimaging literature investigating the effects of CBD on the brain in healthy participants. We then theorise the potential neurobiological mechanisms by which CBD may ameliorate various symptoms of AUD.Methods This review was conducted according to the PRISMA guidelines. Terms relating to CBD and neuroimaging were used to search original clinical research published in peer-reviewed journals.Results Of 767 studies identified by our search strategy, 16 studies satisfied our eligibility criteria. The results suggest that CBD modulates γ-Aminobutyric acid and glutamate signaling in the basal ganglia and dorso-medial prefrontal cortex. Furthermore, CBD regulates activity in regions associated with mesocorticolimbic reward pathways; salience, limbic and fronto-striatal networks which are implicated in reward anticipation; emotion regulation; salience processing; and executive functioning.Conclusion CBD appears to modulate neurotransmitter systems and functional connections in brain regions implicated in AUD, suggesting CBD may be used to manage AUD symptomatology.

Parameter Space and Potential for Biomarker Development in 25 Years of fMRI Drug Cue Reactivity: A Systematic Review.

Importance: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. Objective: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. Evidence Review: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. Findings: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. Conclusions and Relevance: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Economic evaluations of alcohol pharmacotherapy: Systematic review of economic evaluations of pharmacotherapy for the treatment of alcohol use disorder.

OBJECTIVE: Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies. METHODS: A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality. RESULTS: A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%. CONCLUSION: Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.

N acetylcysteine in the treatment of alcohol use disorder: a randomized, double-blind, placebo-controlled trial.

N-acetyl cysteine (NAC) is a potent antioxidant that modulates glutamatergic signalling which is thought to play a role in alcohol use disorder (AUD). There have been no clinical trials investigating NAC for AUD. We aimed to conduct a 28 day double-blind, placebo-controlled (PL) randomized trial of NAC in the treatment of AUD (NCT03879759). A total of 42 participants with AUD (56% alcohol-related liver disease) were randomized to receive placebo or NAC 2400 mg/day. Feasibility outcomes included treatment retention and adverse events. Primary clinical outcomes included alcohol consumption (heavy drinking days, standard drinks per drinking day). Secondary clinical outcome measures included craving, liver tests, and psychological outcomes. There were no significant differences in overall retention between treatment groups (χ2(1) = 0.14, P = 0.71: 86% vs 76% for placebo and NAC, respectively). The most commonly reported adverse event in NAC-treated individuals included headache (14%). For standard drinks per drinking day, there was a significant overall effect of time (F = 9.18, P < 0.001), no significant effect of treatment (F = 0.75, P = 0.79), and a significant time x treatment (NAC vs PL) effect (F = 2.73, P < 0.05). For number of heavy drinks per day, there was a significant overall effect of time (F = 3.16, P < 0.05) but no significant effect of treatment or time x treatment (P = 0.17). There were no significant NAC vs PL effects on secondary clinical outcome measures. In the first trial of NAC for the management of AUD, NAC appears to be feasible and safe. Although there was a significant effect of NAC vs placebo on some alcohol measures such as drinks per drinking day, there does appear to be a variable pattern of effect across time suggesting that a larger trial incorporating a longer treatment duration is now required to determine efficacy.

High Risk or Risky Highs: Understanding the Links Between Alcohol and Cannabis Use on the Transition From Suicidal Ideation to Attempts in Australian Men.

Alcohol and cannabis use are consistently associated with greater risk of suicide, particularly among men and in higher-income countries (e.g., Australia). Adult data (n = 7,464) from waves 1 and 2 of Ten to Men: The Australian Longitudinal Study on Male Health were used to explore whether alcohol and/or cannabis use increased the longitudinal risk of a suicide attempt among suicidal ideators. Cannabis use was associated with increased risk of transitioning from suicidal ideation to making a suicide attempt; no association was found for alcohol. Broadly, these findings indicate that greater cannabis but not alcohol use may increase risk of transitioning to making a suicide attempt among those who are thinking about suicide.

Hypothalamic-pituitary-adrenocortical response in alcohol-dependent patients during baclofen treatment and association with clinical outcome: Preliminary results.

Baclofen has been shown to reduce alcohol consumption in some individuals with alcohol use disorder. This preliminary study aimed to evaluate i) the effect of baclofen versus placebo on hypothalamic-pituitary-adrenocortical activity (HPA axis), as measured by cortisol, and ii) the relationship between clinical outcomes such as alcohol consumption on a randomized controlled trial of baclofen (BAC) versus placebo (PL) (Kirsten C. Morley et al., 2018; K. C. Morley, Leung, Baillie, & Haber, 2013). We hypothesized that baclofen will reduce HPA-axis activity following a mild stressor in patients with alcohol dependence. Plasma cortisol levels were taken from N = 25 alcohol-dependent patients at two time points, approximately 60 (pre-MRI scan: PreCortisol) and 180 min (post MRI scan: PostCortisol) following administration of PL, BAC 10 mg, or BAC 25 mg. Participants were followed up for the remaining 10 weeks as part of the trial for clinical outcome (percentage days abstinent). Mixed models revealed a significant main effect of medication on cortisol levels (F = 3.88, p = 0.037), no significant effect of time (F = 0.04, p = 0.84), and a significant time × medication interaction (F = 3.54, p = 0.049). Linear regression (F = 6.98, p = 0.01, R2 = 0.66) revealed that abstinence at follow-up, weighted by gender, was predicted by blunted cortisol response (ß = -0.48 p = 0.023), in addition to medication (ß = 0.73 p = 0.003). In conclusion, our preliminary data suggest that baclofen moderates HPA-axis activity, as measured by blood cortisol, and that these alterations may play a role in long-term treatment response.

Central markers of neuroinflammation in alcohol use disorder: A meta-analysis of neuroimaging, cerebral spinal fluid, and postmortem studies.

INTRODUCTION AND AIMS: There is emerging evidence that heavy long-term alcohol consumption may alter the neuroimmune profile. We conducted a meta-analysis of the association between alcohol use disorder (AUD) and the extent of neuroinflammation using cerebrospinal (CSF), PET (Positron Emission Tomography), and postmortem studies. DESIGN AND METHODS: A comprehensive search of electronic databases was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) for AUD-related terms in combination with neuroinflammatory markers and cytokine- and chemokine-related terms for CSF, PET, and postmortem studies. Participants had to meet established criteria for AUD and/or heavy alcohol consumption with dependence features and be compared with healthy controls. Papers retrieved were assessed for inclusion criteria and a critical appraisal was completed using the Newcastle-Ottawa Scale. A meta-analysis was conducted on postmortem and PET studies. RESULTS: Eleven papers met the inclusion criteria with CSF, PET, and postmortem studies included in the final analysis. Postmortem studies demonstrate significant heterogeneity (𝑄 (14) = 62.02, 𝑝 < 0.001), with the alcohol group showing higher levels of neuroimmune markers than controls (𝑑 = 1.50 [95% CI 0.56, 2.45]). PET studies demonstrated a lower [11 C] PBR28 total volume of distribution (V T ) for translocator protein in the hippocampus (g = -1.95 [95% CI -2.72, -1.18], p < 0.001) of the alcohol group compared to controls. CONCLUSION: There is emerging evidence across multiple diagnostic modalities that alcohol impacts neuroimmune signaling in the human brain.

Impaired Decision-Making and Skin Conductance Responses Are Associated with Reward and Punishment Sensitivity in Individuals with Severe Alcohol Use Disorder.

INTRODUCTION: Individuals with alcohol use disorder (AUD) have difficulties regulating alcohol consumption, despite adverse drinking-related consequences. This may be due to incapacity incorporating previous negative feedback from drinking, resulting in impaired decision-making. METHODS: We assessed whether decision-making is impaired in participants with AUD related to severity of AUD, indexed by severe negative drinking consequences using the Drinkers Inventory of Consequences (DrInC) and reward and punishment sensitivity with the Behavioural Inhibition System Behavioural Activation System (BIS BAS) scales. 36 treatment-seeking alcohol-dependent participants completed the Iowa gambling task (IGT) with skin conductance responses (SCRs) measured continuously as an index of somatic autonomic arousal to evaluate impaired expectancy of negative outcomes. RESULTS: Two-thirds of the sample showed behavioural impairment during the IGT, with greater AUD severity related to worse performance. BIS moderated IGT performance according to severity of AUD, with increased anticipatory SCRs for those with fewer reported DrInC severe consequences. Participants with more DrInC severe consequences showed IGT deficits and reduced SCRs regardless of BIS scores. BAS-Reward was associated with increased anticipatory SCRs to disadvantageous deck choices among those with lower AUD severity, while SCRs did not differ related to AUD severity for reward outcomes. DISCUSSION: Effective decision-making in the IGT and adaptive somatic responses were moderated by punishment sensitivity contingent on severity of AUD in these drinkers, with impairments in expectancy to negative outcomes from risky choices, including reduced somatic responses, resulting in poor decision-making processes that may help explain impaired drinking and worse drinking-related consequences.

Assessing the validity of the Wechsler Adult Intelligence Scale (WAIS-IV) in predicting completion in a long-term residential rehabilitation for substance use problems.

BACKGROUND: We aimed to examine the predictive validity of the Weschler Adult Intelligence Scale (WAIS-IV) in predicting treatment completion, over and above educational status. METHODS: One hundred and ninety-six (N = 196) individuals from the Odyssey House Residential Rehabilitation Program, NSW, Australia between 2010 and 2016 were administered a structured interview including substance use disorders and the Verbal Comprehension (VCI), Perceptual Reasoning (PRI), Working Memory (WMI), and Processing Speed (PSI) domains of the WAIS-IV. RESULTS: There were significant differences between our clinical sample and the population norm with respect to the proportion below the mean for PSI (z = 12.27, p < .001), VCI (z = 2.33, p < .02) but not for WMI (z = 1.67, p < .10) or PRI (z = -1.76, p < .08). The WAIS-IV subscales did not significantly predict treatment completion (p's > .16) over and above educational status (p < .01). CONCLUSIONS: Our findings suggest that in clients in drug and alcohol rehabilitation settings a combination of skills may be impacted including Verbal Comprehension and Processing Speed. Moreover, our findings also suggest that WAIS-IV subscales do not predict treatment completion in a drug and alcohol residential setting, over and above a brief assessment of educational status.

Geographical variation in implementation of the Pathways to Comorbidity Care program in Australian drug and alcohol services.

AIM: Comorbid drug and alcohol and mental health disorders are highly prevalent. Significant gaps in service provision make this problem particularly difficult to address in regional Australia. The Pathways to Comorbidity Care (PCC) program was designed to improve management of comorbidity by outpatient drug and alcohol clinicians in New South Wales, Australia. This paper uses the Consolidated Framework for Implementation Research (CFIR) to evaluate variations in implementation outcomes across geographically diverse services. METHODS: Twenty clinicians across three drug and alcohol services from metropolitan, outer metropolitan and regional geographic locations were engaged at multiple levels of influence (directors, managers, clinicians) during the implementation of the multimodal PCC training package. The CFIR guided the development of self-report measures and semi-structured interviews evaluating implementation of the PCC training, and disparities in implementation barriers and facilitators were determined. RESULTS: Metropolitan clinicians identified less barriers than regional clinicians on several intervention characteristics (adaptability, complexity, design quality and packaging), as well as outer setting (peer pressure), inner setting (implementation climate, staff incentives, leadership engagement, available resources) and process (planning, opinion leaders, executing) domains. Regional clinicians evaluated the networks and communications construct more favourably. CONCLUSIONS: Specific barriers identified more strongly by regional clinicians included the importance of communication with local clinicians and leadership about the practicalities of incorporating the approach into routine practice (allocation of time, increased accessibility of implementation team). Metropolitan clinicians provided more favourable evaluations of the package design, implementation climate and specific implementation processes such as a clear and informative implementation plan.

Sex differences in the interrelations between stress, craving and alcohol consumption across individuals and time during baclofen treatment for alcohol dependence.

AIMS: Recent studies have suggested that females respond more favourably to baclofen treatment for alcohol use disorder. Females are generally more likely to drink to regulate stress reactivity and negative affect. This study thus aimed to evaluate the role of sex on the effect of baclofen on the relationship between daily alcohol consumption, stress and craving. METHODS: A network analysis of fluctuations using vectorized autoregressive modelling was used to explore the relationship between daily surveys of alcohol consumption, stress and craving from daily diary data over 84 days from a randomised controlled trial of baclofen (30 mg or 75 mg per day) versus placebo in 104 participants with alcohol dependence (1, 2). Symptom interrelations across patients and across time were examined including temporal networks (time lagged), contemporaneous and between-subjects networks, and were examined for placebo and baclofen stratified by sex. RESULTS: Overall, between persons, there was a significant relationship between stress and drinking in placebo treated individuals in females (r = -0.70, p < 0.001) but not males (r = 0.32, p = 0.054) that was not observed in baclofen treated individuals. No relationship was observed between stress and drinking in the baclofen group for either sex (p's < 0.45). DISCUSSION: There appears to be some sex-specific differences whereby baclofen abolishes an overall association between stress and drinking in females, but this is not observed in males. Network analyses may assist in elucidating the mechanism of action of alcohol pharmacotherapies such as baclofen and understanding which symptoms and mechanisms are key for effective interventions.

The Association Between Problematic Use of Alcohol and Drugs and Repeat Self-Harm and Suicidal Ideation.

Aims: We investigated the association between problematic use of alcohol and/or drugs (PUAD) and the incidence, urgency, and mode of discharge for a subsequent episode of self-harm (SH) or suicidal ideation (SI). Methods: This was a retrospective population-based cohort study of individuals admitted to hospital for an index episode of SH/SI (2010-2014) using linked data from hospital admissions and emergency department (ED) presentations. The outcome variables were (1) subsequent presentation to the ED for SH/SI, (2) triage category, and (3) mode of departure. Key predictors were PUAD. Results: In total, 23,007 individuals were admitted to hospital for an index SH/SI, of whom 8% had a subsequent presentation to an ED for SH/SI within a year. The odds of subsequent presentation was increased in those with problematic alcohol use (AOR 1.62, 95% CI 1.36, 1.92), drug use (AOR 1.28, 95% CI 1.07, 1.53), and mental health diagnoses (AOR 1.63, 95% CI 1.44, 1.85). Those with problematic alcohol use were more likely to be assigned to the most urgent triage categories (AOR 1.84, 95% CI 1.32, 2.56). Limitations: Defining SH and PUAD using administrative data is challenging, and the true prevalence is likely to be underestimated. Conclusion: The findings underscore the importance of drug health intervention as a key component of self-harm prevention.

The role of impulsivity in the relationship between affect and alcohol consumption in young adults.

BACKGROUND: Theoretical models of alcohol use posit that individuals consume alcohol to ameliorate negative affect or to heighten positive affect. It is important, however, to consider the influence of factors that may determine an individual's tendency to consume excessive amounts of alcohol under positive and negative circumstances. Thus, the current study examined a large sample of young adults to clarify whether positive and negative affect predict total alcohol consumption on drinking days and whether facets of impulsivity moderate these relationships. METHODS: Six-hundred ninety-three young adults (Mage = 19.71 years, SD = 2.04; female = 62.9%) completed the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales at baseline followed by daily measures of positive and negative affect and self-reported alcohol use for 13 days. Generalized linear mixed models were specified to assess the role of pre-consumption affect on total drinks consumed across drinking days and to determine the moderating effect of each BIS/BAS subscale. RESULTS: Participants were significantly more likely to drink in greater quantities on occasions preceded by higher positive affect but not negative affect. While fun-seeking positively predicted total drinks consumed, there were no significant interaction effects between the BIS/BAS subscales and affect on total drinks consumed. CONCLUSIONS: These findings challenge existing affect regulation models and have implications for ecological momentary interventions aimed at addressing hazardous drinking behaviors.

Can we enhance the clinical efficacy of cognitive and psychological approaches to treat substance use disorders through understanding their neurobiological mechanisms?

Despite decades of research in the field of addiction, relapse rates for substance use disorders remain high. Consequently, there has been growing focus on providing evidence-based treatments for substance use disorders, resulting in the increased development and use of cognitive and psychological interventions. Such treatment approaches, including contingency management, community-reinforcement approach, and cognitive bias modification, have shown promising clinical efficacy in reducing substance use and promoting abstinence during treatment. However, these interventions are still somewhat limited in achieving sustained periods of abstinence post-treatment. The neurobiological mechanisms underpinning these treatment approaches remain largely unknown and under-studied, in part, due to a lack of translational animal models. The adoption of a reverse translational approach may assist in development of more representative models that can facilitate elucidation of the mechanisms behind these clinically relevant interventions. This review examines our current understanding of addiction neurobiology from clinical, preclinical research and existing animal models, and considers how the efficacy of such behavioral-oriented interventions alone, or in combination with pharmacotherapy, may be enhanced to improve treatment outcomes.

Relationship between clinician-level attributes and implementation outcomes from the Pathways to Comorbidity Care training program.

BACKGROUND: The process of determining the best strategy for increasing the uptake of evidence-based practice might be improved through an understanding of relevant clinician-level factors. The Pathways to Comorbidity Care (PCC) training program (Louie E, et al., J Dual Diagnosis 17:304-12, 2021) aimed to facilitate integrated management of comorbid drug and alcohol and mental disorders amongst drug and alcohol clinicians. We hypothesised that uptake of integrated management of comorbidity following the implementation of the PCC program would be associated with clinician-level: (i) demographics (gender, education, experience), (ii) attitudes (evidence-based practice, therapist manuals, counselling self-efficacy), and (iii) organisational readiness to change. METHODS: Twenty clinicians participated in the 9-month PCC training program. Attitudes towards evidence-based practices and psychotherapist manuals, self-efficacy, and organisational readiness to change, along with demographics, were measured at baseline. At follow-up, change in Comorbidity Practice (CoP) scores related to integrated comorbidity management were obtained using a file audit checklist and categorised into high (at least 60% increase in CoP), medium or low (a decrease of - 20% or less in CoP). Clinician-level characteristics were examined across the implementation categories. RESULTS: There were no significant differences found between implementation groups on sociodemographic variables (p's > 0.30), attitudes to evidence-based practices, attitudes to therapist manuals, and self-efficacy (p's > 0.52). The high implementation group demonstrated significantly higher scores on leadership practices aspect of organisational readiness to change relative to the low and medium implementation group ((F(2, 16) = 3.63, p = 0.05; Cohen's d = .31) but not on the other subscales (p's > 0.07). CONCLUSIONS: Confidence that leadership will play a positive role in the implementation process may improve effectiveness of comorbidity training programs for drug and alcohol clinicians. On the other hand, contrary to our hypothesis, counselling self-efficacy, evidence-based practice attitudes, attitudes towards therapist manuals, gender, education and experience were not distinguishing factors.

A systematic review of the perceptions and attitudes of mental health nurses towards alcohol and other drug use in mental health clients.

Mental and substance use disorders are leading contributing factors for the Australian non-fatal burden of disease. These disorders frequently co-occur in the mental health population, and mental health nurses are the largest group of professionals treating dual diagnosis. A comprehensive understanding of mental health nurses' attitudes and perceptions is required to inform future implementation of dual diagnosis training programs. A systematic literature review of sources derived from electronic databases including Medline, CINAHL, SCOPUS review, and PsychINFO, along with Connected Papers. Selection criteria included a focus on mental health nurses' attitudes towards dual diagnosis of mental illness and substance use. Extracted data was qualitatively synthesized. Of the 5232 articles retrieved initially, 12 were included in the review. Four themes emerged from the synthesis: drug and alcohol use among mental health consumers (seven studies), caring for dual diagnosis consumers (eight studies), role perception (six studies), and treatment optimism (five studies). Salient beliefs included substance use as a self-inflicted choice (71%) or a form of 'self-medication' (29%); a lack of willingness to provide care (75%), or a strong commitment to care (25%); greater comfort with screening and acute medical management rather than ongoing management (83%); and pessimism about treatment effectiveness (100%). Mental health nurses' beliefs and attitudes towards dual diagnosis were often negative, which is likely to result in poor quality care and treatment outcomes. However, the lack of recent studies in this research area indicates the need for up-to-date knowledge that can inform the development of training programs.

The evaluation of the role of technology in the pathways to comorbidity care implementation project to improve management of comorbid substance use and mental disorders.

In substance use treatment settings, comorbid mental health problems can occur in up to 70% of people. An integrated approach for managing comorbidity, implementing evidence-based intervention in drug and alcohol settings, remains problematic. Technology can help in adopting evidence-based practice to implement effective treatment healthcare pathways. This study sought to examine aspects of tailored portal utilization (barriers and facilitators) by participants taking part in a program aimed at improving the implementation of evidence-based practice for comorbidity management Pathways to Comorbidity Care (PCC). Method: A self-report questionnaire and a semi-structured interview were designed to measure clinician satisfaction with the PCC portal and e-resources throughout a 9-month intervention. An adapted version of the "Non-adoption, Abandonment, Scale-up, Spread and, Sustainability" (NASSS) framework facilitated discussion of the findings. Results: Twenty participants from drug and alcohol services responded to all measures. Facilitators included: (i). clinician acceptance of the portal; (ii). guidance from the clinical supervisor or champion to encourage e-resource use. Barriers included: (i). complexity of the illness (condition); (ii). participants' preference (adopter system) for face-to-face resources and training modes; and, (iii). lack of face-to-face training on how to use the portal (technology and organization). Conclusion: Based on the NASSS framework, we identified several barriers and facilitators of the use of the portal including the complexity of illness, lack of face-to-face training, and clinician preference for training mediums. Recommendations include ongoing organizational support, in-house clinical supervision, and consultation with clinical providers to assist in the development of tailored e-health resources and open training opportunities on how to operate and effectively utilize these resources.

Sex as a Potential Moderator for Baclofen Response in the Treatment of Alcohol Dependence.

Background and Aims: Recent studies indicate that sex may moderate the response to baclofen in the treatment of alcohol use disorder (AUD). We conducted a secondary analysis of a double-blind randomized controlled trial, Baclofen in the treatment of Alcohol Liver Disease (BacALD), to examine the moderating role of sex on treatment response to baclofen in reducing alcohol consumption. Methods: Alcohol-dependent patients (n = 104 including 74 men and 30 women) were treated for 12 weeks with baclofen (30 mg/day or 75 mg) or placebo. Predefined primary outcomes included time to lapse (any drinking) and relapse (≥ 5 drinks per day in men and ≥ 4drinks per day in women). Other outcomes included drinks per drinking day, the number of heavy drinking days, and percentage of days abstinent. We also examined the frequency of adverse events with an exploratory dose-response analysis. Results: There was a main effect of baclofen for days to first lapse for women (Log Rank: χ2 = 6.23, p = 0.01, d = 0.49) but not for men (Log Rank: χ2 = 2.48, p = 0.12, d = 0.22) and a marginal effect of baclofen for days to first relapse for women (Log Rank: χ2 = 3.15, p = 0.08, d = 0.27) but not for men (Log Rank: χ2 = 2.03, p = 0.16, d = 0.17). There were no significant effects of sex on the frequency of adverse events reported for the combined-dose or between-dose analysis (all p > 0.44). Conclusion: Baclofen significantly delayed the time to lapse for women but not male participants. These findings provide some support for the hypothesis that sex may be a potential moderator of baclofen response in the treatment of AUD. Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01711125, identifier: NCT01711125.