Gait ataxia in alcohol use disorder: A systematic review.

OBJECTIVE: A severe and long-term alcohol use can have adverse effects on lower limb function. Over time, some individuals may develop gait ataxia, which refers to the impairment of controlled lower body movements that are important for walking and maintaining proper gait. Gait ataxia is well-documented in patients who have been diagnosed with alcohol-related Wernicke-Korsakoff syndrome (WKS); however, less is known on how common ataxia is among patients with alcohol use disorder (AUD) without WKS. To date, no study has systematically reviewed the evidence focusing on patients suffering only from AUD. Our aim was to perform a qualitative synthesis of the existing literature examining behavioral signs of gait ataxia among abstinent patients with AUD. METHOD: Two facets were created encompassing keywords for "alcohol use disorder" and "measures of gait ataxia." Databases, including EMBASE, APA PsycInfo, Medline, and Cochrane Library, were searched for studies, and a quality assessment was performed. RESULTS: Ten studies were identified (37 ≥ ns ≤ 247), which were all rated as being of moderate (N = 7) to good quality (N = 3). The age range was 31.4-53.4 years (weighted mean age: 53.6 years), and 78.3% of the participants were male. Eight studies found that patients with AUD and without WKS exhibited behavioral signs of gait ataxia. CONCLUSIONS: Although there is evidence of gait ataxia among patients with AUD, heterogeneous results and methodological shortcomings such as lack of screening for neurocognitive deficits deem these findings preliminary and highlight the need for more research in the future. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Transferring the approach avoidance task into virtual reality: a study in patients with alcohol use disorder versus healthy controls.

Study aims were to (I) transfer the measurement of the approach bias (Apb) related to alcoholic stimuli via the Approach Avoidance Task (AAT) into Virtual Reality (VR), (II) check whether measuring Apb in VR leads to similar or different results compared to the classical PC-based version, (III) check the validity of VR versus PC-based bias scores in terms of relatedness to clinical variables. Different 'grasping-conditions' were tested and contrasted in VR concerning (Ia) feasibility (performance): (1) never grasp, (2) always grasp, (3) grasp when PULLing stimuli towards oneself. (Ib) Differences in the bias scores between patients with alcohol use disorder (AUD) and healthy controls (HC) were examined for each grasping-condition. (II) PC-based bias scores were computed and contrasted for AUD versus HC. (III) Correlations of the different VR- versus PC-based bias scores with AUD symptom severity and impulsivity were checked to evaluate validity. (Ia) Grasping-condition 1, followed by 3, showed acceptable (> 50%) and good (> 80%) rates of correct performances allowing for robust median estimation. (Ib) Significant differences in the resulting bias scores emerged between AUD and HC only for grasping-condition 1 (p = 0.034) and 3 at trend-level (p = 0.093). For grasping-condition 1 the Apb Median for AUD was different from zero at a non-significant trend-level (p = 0.064). (II) The PC-based bias scores did not discriminate between AUD versus HC groups. (III) Grasping-condition 1 and 3 VR-based bias scores correlated significantly with impulsivity. In sum, transferring the AAT into VR is feasible, valid, and best implemented without an additional grasping-component when using the VR-controller. This way of Apb assessment represents a viable, perhaps even superior, alternative to PC-based assessments. Trial registration The trial was pre-registered at AsPredicted #76854: 'Transferring the approach avoidance task into virtual reality', 10/13/2021; prior to any analyses being undertaken.

The effectiveness of oxytocin for treating substance use disorders:A systematic review of randomized placebo-controlled trials.

Oxytocin is gaining traction in the treatment of various substance use disorders (SUD). We performed a systematic review assessing the efficacy of oxytocin for treating different SUD. The electronic databases MEDLINE, EMBASE, CENTRAL, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials examining the effects of oxytocin vs. placebo in SUD samples. Quality assessment was conducted using a Cochrane validated checklist. A total of 17 trials with unique samples were identified. These were conducted on participants with SUD involving alcohol (n = 5), opioids (n = 3), opioids and/or cocaine/other stimulants (n = 3), cannabis (n = 2), or nicotine (n = 4). Across the SUD-groups, oxytocin reduced withdrawal symptoms (3/5 trials), negative emotional states (4/11 trials), cravings (4/11 trials), cue-induced cravings (4/7 trials), and consumption (4/8 trials). Sixteen trials had an overall considerable risk of bias. In conclusion, although oxytocin showed some promising therapeutic effects, the findings are too inconsistent and the trials too heterogeneous to derive any firm conclusions. Sounder methodological and well-powered trials are warranted.

Mentalization-oriented psychodynamic group therapy for patients with personality disorders: a naturalistic prospective cohort study.

OBJECTIVES: Patients with personality disorders (PDs) are often treated with non-manualized psychodynamic group therapy (PDT) lasting for several years. Non-manualized PDT often combines a variety of therapeutic approaches from different PDT traditions, including mentalization-based therapy. Currently, little is known about the effect of this long-term, costly treatment. This study investigated the extent to which patients with different PDs benefit from mentalization-oriented PDT as it is implemented in clinical practice in terms of symptom severity, interpersonal problems, and general functioning. METHODS: The design was a naturalistic, prospective cohort study. Seventy-five consecutive PD patients were assessed before treatment with the Symptom Checklist-90 Revised (SCL-90-R) as the primary outcome measure and the Inventory of Interpersonal Problems (IIP) and Global Assessment of Functioning (GAF) as secondary outcome measures. The sample was repeatedly assessed every 12 months for up to 36 months. Paired t-tests were applied to examine the effectiveness of the intervention. RESULTS: Among completers (n = 42; 56%), improvement was observed on the SCL-90-R: Global Severity Index (mean change = -0.45 [95% CI = -0.72, -0.19]; Cohen's d = -0.55), Positive Symptom Distress Index (-0.40 [-0.63, -0.17]; -0.56); Positive Symptoms Total (-10.70 [-17.31, -4.09]; -0.52). Secondary outcomes also improved: IIP-total (mean change = -0.50 [95%CI = -0.74, -0.25]; Cohen's d = -0.66); GAF-Functioning (8.79 [6.32, 11.27]; 1.15); and GAF-Symptoms (10.67 [8.09, 13.25]; 1.34). CONCLUSIONS: Completers improved on symptom severity, interpersonal problems, and general functioning, with within-group effect sizes ranging from medium to large. Approximately half the sample dropped out, suggesting that mentalization-oriented PDT spanning several years may be unrealistic for many patients with PD. Significant outcomesThere are no clear guidelines for psychological interventions targeting personality disorders (PDs), and currently eclectic and non-manualized psychodynamic approaches lasting for up to 3 years are prevailing in some clinical practices.Although this treatment approach may have an effect on compliant patients, the high drop-out rate indicates that it may not be suitable for a large proportion of PD patients since it requires long-term commitment. Furthermore, it is difficult to identify the content of the non-manualized psychodynamic therapy and what helps the patients.More specific clinical guidelines emphasizing the application of evidence-based treatments or at least manualized treatments are warranted for the treatment of emotionally unstable PDs and other PDs. LimitationsThe naturalistic study design, without any control group, limits conclusions about mechanisms of action of the intervention.Since the intervention was not manualized, it is unknown exactly which treatment was actually administered, which reduces external validity.The outcomes are based on completer data of a relatively small sample size with high drop-out rate.

Pharmacological treatment of alcohol use disorder in patients with psychotic disorders: A systematic review.

BACKGROUND: Patients with psychotic disorders (PD) often have comorbid alcohol use dis- order (AUD), which is typically treated pharmacologically. Up till now, no systematic review has ex- amined the effectiveness and safety of AUD treatment in PD patients.

Objectives: This study aimed to systematically review the literature on (1) the effects of pharmacolog- ical treatments for AUD on drinking outcomes, (2) the side effects of the drugs, and (3) the effects of polypharmacy in patients with comorbid AUD and PD.

Methods: Bibliographic searches were conducted in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsycINFO. At least two reviewers extracted the data, assessed the risk of bi- as, and performed the qualitative synthesis of the collected evidence.

Results: Twelve eligible studies were identified, half being randomized controlled trials (RCTs). Three studies examined disulfiram, nine naltrexone, two acamprosate, and one nalmefene by comparing the effects of treatment to placebo, baseline, or other pharmacological agents. Disulfiram and naltrexone were shown to reduce alcohol intake. Regarding acamprosate, the findings were mixed. Nalmefene decreased alcohol intake. All pharmacological agents appeared safe to use as AUD mono- therapy, but cardiac events were reported when combining naltrexone and disulfiram. Nine studies had a high risk of bias, and three had some other concerns.

Conclusion: The studies provide tentative support for the use of naltrexone and disulfiram in this population, although combinations of pharmacological AUD treatments and other polypharmacy remain unexplored. The studies had high adherence rates that are hardly replicable in real-world settings.

Comparison of self-reported alcohol consumption and ethyl glucuronide in hair in a sample of 60+ year -olds treated for DSM-5 alcohol use disorder.

There is a lack of evidence for the consistency between self-reported alcohol consumption (SRAC) and concentrations of ethyl glucuronide in hair (hEtG) among elderly patients treated exclusively for alcohol use disorder (AUD). Hence, this study assessed the consistency between these two measures in these patients. A total of 190 patients with AUD were assessed for SRAC using Form 90 and hEtG, 14 or 22 weeks after treatment conclusion. Patients were grouped according to SRAC (g/day) and corresponding hEtG concentrations (pg/mg): 0 and <5 (abstinence), 0.1-14.3 and 5.0-9.9 (low consumption), 14.4-21.4 and 10.0-15.9 (moderate consumption), 21.5-59.9 and 16.0-30 (high consumption) and ≥60 and >30 (excessive consumption). The extent of underreporting and overreporting was examined by crosstabulations, and inter-rater reliability was reported by kappa correlations. Associations and effect modification were examined by conditional logistic regression. Due to multitesting, p-values ≤0.01 were considered significant. Underreporting was found in 96 patients (50.5%) and overreporting in 41 patients (21.6%). The kappa coefficients varied between 0.19 and 0.34. HEtG was more likely to detect low, moderate and high alcohol consumption compared with SRAC (ORs between 5.1 and 12.6, all p-values <0.01), but SRAC and hEtG did not differ significantly with respect to identification of abstinence (OR = 1.9, p = 0.05). Inconsistency between the outcome measures was found in a considerable number of the patients. More studies examining the consistency between SRAC and specific direct biomarkers of alcohol in this population seem warranted.

Personality-Related Factors and Depressive Symptomatology Predict Behavioral Control in Patients With Alcohol Use Disorders.

In the face of increasing social, economic, and health consequences of alcohol use disorders (AUDs) and limited effects of available treatment options, the search for novel prevention and management methods continues to remain a timely and valid endeavor. This, however, requires a better grasp of the theoretical framework underlying addiction mechanisms. With the goal to extend the existing body of evidence on AUDs, we set out to investigate the effect of personality-related factors and depressive symptomatology on (i) impulsivity, (ii) cognitive response inhibition, and (iii) the links between the two measures of behavioral control (different facets of impulsivity and response inhibition) in a treatment-seeking AUD sample. To this end, 53 male (n = 45) and female (n = 8) inpatients at an alcohol rehabilitation center completed three self-report questionnaires: the International Personality Item Pool (IPIP-50), the Beck Depression Inventory Second Edition (BDI-II) and the Barratt Impulsiveness Scale (BIS-11) and performed one behavioral task-an alcohol go/no go task. Regression analyses revealed conscientiousness, intellect, and depression level to be important potential predictors of self-report impulsivity and processing speed in recovering drinkers. No significant links were observed between the two measures of behavioral control, thus complementing evidence that while they both encompass behavioral under-regulation, they may indeed represent distinct psychological constructs.

Effect of Sleep Disturbance Symptoms on Treatment Outcome in Blended Cognitive Behavioral Therapy for Depression (E-COMPARED Study): Secondary Analysis.

BACKGROUND: Sleep disturbance symptoms are common in major depressive disorder (MDD) and have been found to hamper the treatment effect of conventional face-to-face psychological treatments such as cognitive behavioral therapy. To increase the dissemination of evidence-based treatment, blended cognitive behavioral therapy (bCBT) consisting of web-based and face-to-face treatment is on the rise for patients with MDD. To date, no study has examined whether sleep disturbance symptoms have an impact on bCBT treatment outcomes and whether it affects bCBT and treatment-as-usual (TAU) equally. OBJECTIVE: The objectives of this study are to investigate whether baseline sleep disturbance symptoms have an impact on treatment outcomes independent of treatment modality and whether sleep disturbance symptoms impact bCBT and TAU in routine care equally. METHODS: The study was based on data from the E-COMPARED (European Comparative Effectiveness Research on Blended Depression Treatment Versus Treatment-as-Usual) study, a 2-arm, multisite, parallel randomized controlled, noninferiority trial. A total of 943 outpatients with MDD were randomized to either bCBT (476/943, 50.5%) or TAU consisting of routine clinical MDD treatment (467/943, 49.5%). The primary outcome of this study was the change in depression symptom severity at the 12-month follow-up. The secondary outcomes were the change in depression symptom severity at the 3- and 6-month follow-up and MDD diagnoses at the 12-month follow-up, assessed using the Patient Health Questionnaire-9 and Mini-International Neuropsychiatric Interview, respectively. Mixed effects models were used to examine the association of sleep disturbance symptoms with treatment outcome and treatment modality over time. RESULTS: Of the 943 patients recruited for the study, 558 (59.2%) completed the 12-month follow-up assessment. In the total sample, baseline sleep disturbance symptoms did not significantly affect change in depressive symptom severity at the 12-month follow-up (ß=.16, 95% CI -0.04 to 0.36). However, baseline sleep disturbance symptoms were negatively associated with treatment outcome for bCBT (ß=.49, 95% CI 0.22-0.76) but not for TAU (ß=-.23, 95% CI -0.50 to 0.05) at the 12-month follow-up, even when adjusting for baseline depression symptom severity. The same result was seen for the effect of sleep disturbance symptoms on the presence of depression measured with Mini-International Neuropsychiatric Interview at the 12-month follow-up. However, for both treatment formats, baseline sleep disturbance symptoms were not associated with depression symptom severity at either the 3- (ß=.06, 95% CI -0.11 to 0.23) or 6-month (ß=.09, 95% CI -0.10 to 0.28) follow-up. CONCLUSIONS: Baseline sleep disturbance symptoms may have a negative impact on long-term treatment outcomes in bCBT for MDD. This effect was not observed for TAU. These findings suggest that special attention to sleep disturbance symptoms might be warranted when MDD is treated with bCBT. Future studies should investigate the effect of implementing modules specifically targeting sleep disturbance symptoms in bCBT for MDD to improve long-term prognosis.

Pharmacological compounds targeting emotional cognition in alcohol use disorder: A systematic review.

Non-emotional (e.g., executive functions) and emotional cognitive (e.g., facial emotion recognition) impairments are a well-known aspect of alcohol use disorder (AUD). These deficits may impede on treatment outcomes, increase the risk of relapse, and lead to socio-occupational disabilities. Previous systematic reviews have examined the effectiveness of cognitive enhancing pharmacological agents (CEPAs) targeting non-emotional, but not emotional, cognition in AUD. Our aim was to systematically review the effectiveness of CEPAs targeting emotional cognition in subclinical and clinical AUD populations. A qualitative synthesis of controlled trials was conducted, and the studies were assessed for risk of bias. Eight studies were eligible (15 ≤ ns ≤ 143), and they all had a moderate risk of bias. Modafinil and nalmefene were the most examined agents, with the findings suggesting a potential beneficial effect of the agents on implicit emotional domains (i.e., reward processing). Methodological shortcomings and heterogeneous findings across the studies do not allow inferences about the effectiveness of these compounds in AUD. Future studies should examine CEPAs targeting emotional cognition in more detail.

Eating disorders and subsequent risk of substance use disorders involving illicit drugs: a Danish nationwide register-based cohort study.

PURPOSE: No study has investigated the ongoing risk of substance use disorders involving illicit drugs (ISUD) after first eating disorder (ED) and whether the pattern of risk differs according to types of ED and ISUD. Therefore, we aimed to longitudinally assess the risk of a subsequent diagnosis of any ISUD (pooled category) and specific ISUD after a first-time diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or unspecified ED (USED). METHODS: A retrospective cohort study using data from Danish nationwide registers identified 20,759 ED patients and 83,038 matched controls (1:4 ratio). Risk of any ISUD diagnosis after first ED diagnosis was estimated by generating hazard ratios (HR). Logistic regression was applied to assess associations between each ED and specific ISUD. RESULTS: Patients with AN, BN, and USED (without a prior ISUD diagnosis) exhibited an increased relative risk of a subsequent diagnosis of any ISUD compared with respective controls, and the elevated risk persisted over 10 years (AN, adjusted HRs ranging from 1.60 [99% CI 1.15-2.24] to 5.16 [3.14-8.47]; BN, 2.35 [1.46-3.79] to 14.24 [6.88-29.47]; USED, 2.86 [1.35-3.79] to 8.56 [3.31-29.47]). The highest estimates were observed during the first year of follow-up. Each ED type was associated with an increased likelihood of all types of ISUD. AN and USED were most strongly associated with sedatives/hypnotics, BN with other illegal substances (e.g., ecstasy and hallucinogens). CONCLUSIONS: ED patients have a considerable risk for subsequent ISUD. Prevention efforts and treatment targeting ISUD are likely required to improve ED treatment prognosis.

The Impact of Alcohol and Other Substance Use Disorders on Mortality in Patients With Eating Disorders: A Nationwide Register-Based Retrospective Cohort Study.

OBJECTIVE: Research is lacking on the contribution of different types of substance use disorders (SUDs) to excess mortality across the full spectrum of eating disorders. The authors assessed the association of alcohol use disorders and other SUDs with mortality in anorexia nervosa, bulimia nervosa, and unspecified eating disorder compared with matched control subjects. METHODS: A retrospective cohort study was conducted using Danish nationwide registers. The study included 20,759 patients with eating disorders and 83,036 matched control subjects. Hazard ratios were calculated to compare all-cause mortality risk between eating disorder patients and control subjects both with and without a lifetime SUD diagnosis (abuse or dependence of alcohol, cannabis, or hard drugs). RESULTS: For patients with each type of eating disorder, a higher risk of all-cause mortality was observed relative to control subjects without SUDs among those who abused alcohol and/or cannabis (adjusted hazard ratios for the anorexia nervosa, bulimia nervosa, and unspecified eating disorder patients, respectively, were 11.28 [95% CI=7.01, 18.16], 5.86 [95% CI=3.37, 10.1], and 10.86 [95% CI=6.74, 17.50]), or hard drugs alone or in combination with alcohol and/or cannabis (adjusted hazard ratios, respectively, were 22.34 [95% CI=15.13, 33.00], 11.43 [95% CI=7.14, 18.28], and 15.53 [95% CI=10.15, 23.78]), than in those without SUDs (adjusted hazard ratios, respectively, were 3.21 [95% CI=2.43, 4.23], 1.24 [95% CI=0.88, 1.77], and 4.75 [95% CI=3.57, 6.31]). Control subjects with SUDs also exhibited an elevated risk of all-cause mortality relative to control subjects without SUDs, although to a much lesser extent than eating disorder patients with SUDs. CONCLUSIONS: SUDs have an additive effect on excess mortality in patients with eating disorders. The prevention and treatment of SUDs in this patient group is thus imperative to reduce mortality.

Does receiving an eating disorder diagnosis increase the risk of a subsequent alcohol use disorder? A Danish nationwide register-based cohort study.

BACKGROUND AND AIM: No large-scale, longitudinal clinical study has examined whether patients with different types of eating disorders (ED) have an increased risk of a subsequent alcohol use disorder (AUD). This study aimed to assess the ongoing risk of receiving a diagnosis of AUD following a first-time diagnosis of anorexia nervosa (AN), bulimia nervosa (BN), or unspecified ED (USED). DESIGN: Retrospective cohort study. SETTING: Danish nationwide registries, January 1994 to December 2018. PARTICIPANTS: A total of 20 759 ED patients and 83 036 controls were followed from the date of first ED diagnosis (index date) until the date of first AUD diagnosis, death, emigration, or the end of the study. Controls were selected in a 1:4 ratio and matched on month and year of birth, gender and ethnicity. MEASUREMENTS: We obtained data on ED (AN, BN, USED; exposure) and AUD (abuse/dependence; outcome) diagnoses as well as sociodemographics and other psychiatric diagnoses. Time to AUD was generated from the index date. Risk of AUD after the index date was assessed among those without a prior AUD diagnosis while adjusting for sociodemographics and prior psychiatric diagnoses. FINDINGS: Compared with controls, an increased relative risk of AUD after the index date was observed in AN patients throughout the study lasting 15 + years (adjusted hazard ratios [HRs] ranging from 2.49 [99% CI = 1.46, 4.25] to 6.83 [2.84, 16.41]), in BN patients during the first year of follow-up and from 2 years onward (2.72 [1.66, 4.44] to 17.44 [6.01, 50.63]), and in USED patients during the first year and 2-15 years of follow-up (2.52 [1.54, 4.14] to 14.17 [5.86, 34.27]). In all three groups, estimates were highest during the first year, particularly among BN patients. CONCLUSIONS: Patients with anorexia nervosa, bulimia nervosa, or unspecified eating disorders appear to have an increased ongoing risk of receiving a diagnosis of alcohol use disorder following their first eating disorder diagnosis compared with controls.

Relapse prevention for alcohol use disorders: combined acamprosate and cue exposure therapy as aftercare.

AIMS: Many patients with alcohol use disorders are challenged by cravings leading to repeated relapses. Both cue exposure therapy (CET) and acamprosate target alcohol cravings and are often combined (CET + acamprosate). The main aim of this study was to investigate whether aftercare treatment consisting of CET combined with acamprosate is equivalent to (A) CET as monotherapy, (B) aftercare as usual (AAU) as monotherapy or (C) AAU combined with acamprosate. METHODS: Patients were randomized to receive either CET with urge-specific coping skills (USCS) as aftercare or AAU. Acamprosate prescription data were extracted from patient case records. Alcohol consumption, cravings, and USCS were assessed at pre-aftercare, post-aftercare, and 6-month follow-up. RESULTS: Overall, patients increased their alcohol consumption during and following aftercare treatment, thereby relapsing despite any treatment. However, CET + acamprosate achieved greater abstinence compared to AAU + acamprosate at follow-up (p=.047). CET + acamprosate also reduced number of drinking days (p=.020) and number of days with excessive drinking (p=.020) at post-aftercare, when compared to AAU monotherapy. CET monotherapy increased sensible drinking at post-aftercare compared to AAU monotherapy (p=.045) and AAU + acamprosate (p=.047). Only CET monotherapy showed improvement in cravings, when compared to AAU at follow-up (mean urge level: p=.032; peak urge level: p=.014). CONCLUSION: The study showed that CET both as monotherapy and combined with acamprosate was superior to AAU monotherapy and AAU + acamprosate in reducing alcohol consumption. Only CET + acamprosate was capable of reducing alcohol consumption in the longer term, indicating that anti-craving medication may not impede CET from exerting an effect on alcohol consumption. Trial registration: ClinicalTrials.gov ID: NCT02298751 (24/11-2014).

A Randomized Controlled Trial of Attentional Control Training for Treating Alcohol Use Disorder.

Background: There is consistent evidence that community and clinical samples of individuals with an alcohol use disorder (AUD) have attentional biases toward alcohol cues. The alcohol attentional control training program (AACTP) has shown promise for retraining these biases and decreasing alcohol consumption in community samples of excessive drinkers. However, there is a lack of evidence regarding the effectiveness of ACTP in clinical AUD samples. The main aim of the present study is to investigate whether primary pharmacological and psychological, evidence-based alcohol treatment can be enhanced by the addition of a gamified AACTP smartphone application for patients with an AUD. Design and Methods: The study will be implemented as a randomized controlled trial. A total of 317 consecutively enrolled patients with AUD will be recruited from alcohol outpatient clinics in Denmark. Patients will be randomized to one of three groups upon initiation of primary alcohol treatment: Group A: a gamified AACTP smartphone application + treatment as usual (TAU); Group B: a gamified AACTP sham-control application + TAU; or Group C: only TAU. Treatment outcomes will be assessed at baseline, post-treatment, and at 3- and 6-month follow-ups. Repeated measures MANOVA will be used to compare the trajectories of the groups over time on alcohol attentional bias, alcohol craving, and drinking reductions. It is hypothesized that Group A will achieve better treatment outcomes than either Group B or Group C. Perspectives: Because attentional bias for alcohol cues is proportional to the amount of alcohol consumed, and these biases are not addressed within current evidence-based treatment programs, this study is expected to provide new evidence regarding the effectiveness of the gamified AACTP in a clinical population. Furthermore, due to promising results found using AACTP in community samples of excessive drinkers, there is a high probability that the AACTP treatment in this study will also be effective, thereby allowing AACTP to be readily implemented in clinical settings. Finally, we expect that this study will increase the effectiveness of evidence-based AUD treatment and introduce a new, low-cost gamified treatment targeting patients with an AUD. Overall, this study is likely to have an impact at the scientific, clinical, and societal levels. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05102942?term=NCT05102942&draw=2&rank=1, identifier: NCT05102942.

Brain+ AlcoRecover: A Randomized Controlled Pilot-Study and Feasibility Study of Multiple-Domain Cognitive Training Using a Serious Gaming App for Treating Alcohol Use Disorders.

Background: Patients with alcohol use disorder (AUD) exhibit deficits in various cognitive domains, including executive functioning, working memory, and learning and memory, which impede the effectiveness of conventional AUD treatment and enhance relapse. Mobile health (mHealth) services are promising in terms of delivering cognitive training in gamified versions. So far, studies examining the effects of mHealth-based cognitive training in AUD patients have, however, focused on specific rather than multiple cognitive domains and overlooked the importance of clinical outcomes. Furthermore, research has yet to investigate the acceptability and feasibility of this type of cognitive training. Aims: The aims of this pilot study are to examine (1) whether using smartphone-based, multi-domain cognitive training with gamified elements as part of conventional treatment for AUD indicate effect, and (2) whether the intervention is acceptable and feasible as a part of conventional treatment for AUD. Methods: Patients from the alcohol outpatient clinic, Odense Municipality, Denmark will be invited to participate in the study on a consecutive basis until a total of 60 patients have been recruited. The study will be performed as a combined parallel randomized controlled trial (RCT) and qualitative feasibility study. The patients will be randomly assigned to one of two groups. The intervention group (n = 30) will receive smartphone-based, multi-domain cognitive training with gamified elements together with treatment as usual (TAU). The active control group (n = 30) will receive a sham version of the same cognitive training together with TAU. Cognitive outcomes will be assessed via the training application at baseline and post-treatment. Clinical outcomes will be assessed at baseline, post-treatment, and at 6-month follow-up using the Addiction Severity Index. Furthermore, the 30 patients randomized to the intervention group will be invited to participate in the second phase, that is the feasibility study, at post-treatment. A questionnaire inquiring about the use of mHealth treatment in general will be administered. Further, feedback regarding functionality and meaningfulness of the application in addition to other qualitative aspects relating to the use of the application will be collected. The patients will also be asked to provide suggestions about how to improve and potentially implement the tool. Implications: It is anticipated that this pilot study will provide tentative evidence for the effectiveness of smartphone-based, multi-domain cognitive training as well as information about the usability and feasibility of this type of training, including acceptability and compliance. The study will also contribute with feedback derived from the patients about how to improve and implement the tool. If promising, the findings will be used to plan a large-scale RCT. Since cognitive deficits are not addressed in current treatments for AUD, gamified cognitive training delivered through smartphones may increase the effectiveness of current treatment for AUD as well as introduce more mHealth-based treatment that is both accessible and cost-effective.

The Impact of Alcohol and Other Substance Use Disorders on Mortality in Patients With Eating Disorders: A Nationwide Register-Based Retrospective Cohort Study.

OBJECTIVE: Research is lacking on the contribution of different types of substance use disorders (SUDs) to excess mortality across the full spectrum of eating disorders. The authors assessed the association of alcohol use disorders and other SUDs with mortality in anorexia nervosa, bulimia nervosa, and unspecified eating disorder compared with matched control subjects. METHODS: A retrospective cohort study was conducted using Danish nationwide registers. The study included 20,759 patients with eating disorders and 83,036 matched control subjects. Hazard ratios were calculated to compare all-cause mortality risk between eating disorder patients and control subjects both with and without a lifetime SUD diagnosis (abuse or dependence of alcohol, cannabis, or hard drugs). RESULTS: For patients with each type of eating disorder, a higher risk of all-cause mortality was observed relative to control subjects without SUDs among those who abused alcohol and/or cannabis (adjusted hazard ratios for the anorexia nervosa, bulimia nervosa, and unspecified eating disorder patients, respectively, were 11.28 [95% CI=7.01, 18.16], 5.86 [95% CI=3.37, 10.1], and 10.86 [95% CI=6.74, 17.50]), or hard drugs alone or in combination with alcohol and/or cannabis (adjusted hazard ratios, respectively, were 22.34 [95% CI=15.13, 33.00], 11.43 [95% CI=7.14, 18.28], and 15.53 [95% CI=10.15, 23.78]), than in those without SUDs (adjusted hazard ratios, respectively, were 3.21 [95% CI=2.43, 4.23], 1.24 [95% CI=0.88, 1.77], and 4.75 [95% CI=3.57, 6.31]). Control subjects with SUDs also exhibited an elevated risk of all-cause mortality relative to control subjects without SUDs, although to a much lesser extent than eating disorder patients with SUDs. CONCLUSIONS: SUDs have an additive effect on excess mortality in patients with eating disorders. The prevention and treatment of SUDs in this patient group is thus imperative to reduce mortality.

Pharmacological enhancing agents targeting cognition in patients with alcohol-induced neurocognitive disorders: A systematic review.

Debilitating neurocognitive deficits are seen in alcohol use disorders (AUD) and Wernicke-Korsakoff's syndrome (WKS). These shared characteristics suggest a spectrum of alcohol-induced neurocognitive disorders (AIND). Cognitive pharmacological enhancing agents (CPEA) have been examined in the treatment of other psychiatric disorders, but little is known about the effects of these agents on AINDs. Our aim was to synthesize the evidence for the effectiveness of CPEAs on AINDs. Databases were searched for controlled trials examining CPEAs on AUD, WKS, and alcohol-related dementia (ARD). Eligible studies were included in a qualitative synthesis and a quality assessment was conducted. The search identified 23 studies (4 ≤ ns ≤ 98). Evidence suggests that modafinil may improve executive functions in AUD and ARD, but this effect may only be present in patients with severe deficits. The studies were rated as having a moderate risk of bias. Despite the promising effects of modafinil, small samples and inconsistent evidence deem the results preliminary. More research is warranted examining the effects of transdiagnostic CPEAs on deficits across AINDs.

BLEND-A: blending internet treatment into conventional face-to-face treatment for alcohol use disorder - a study protocol.

BACKGROUND: A major challenge to psychological treatment for alcohol use disorder (AUD) is patient non-compliance. A promising new treatment approach that is hypothesized to increase patient compliance is blended treatment, consisting of face-to-face contact with a therapist combined with modules delivered over the internet within the same protocol. While this treatment concept has been developed and proven effective for a variety of mental disorders, it has not yet been examined for AUD. AIMS: The study described in this protocol aims to examine and evaluate patient compliance with blended AUD treatment as well as the clinical and cost effectiveness of such treatment compared to face-to-face treatment only. METHODS: The study design is a pragmatic, stepped-wedge cluster randomized controlled trial. The included outpatient institutions (planned number of patients: n = 1800) will be randomized in clusters to implement either blended AUD treatment or face-to-face treatment only, i.e. treatment as usual (TAU). Both treatment approaches consist of motivational interviewing and cognitive behavioral therapy. Data on sociodemographics, treatment (e.g. intensity, duration), type of treatment conclusion (compliance vs. dropout), alcohol consumption, addiction severity, consequences of drinking, and quality of life, will be collected at treatment entry, at treatment conclusion, and 6 months after treatment conclusion. The primary outcome is compliance at treatment conclusion, and the secondary outcomes include alcohol consumption and quality of life at six-months follow-up. Data will be analyzed with an Intention-to-treat approach by means of generalized linear mixed models with a random effect for cluster and fixed effect for each step. Also, analyses evaluating cost-effectiveness will be conducted. DISCUSSION: Blended treatment may increase treatment compliance and thus improve treatment outcomes due to increased flexibility of the treatment course. Since this study is conducted within an implementation framework it can easily be scaled up, and when successful, blended treatment has the potential to become an alternative offer in many outpatient clinics nationwide and internationally. TRIAL REGISTRATION: Clinicaltrials.gov .: NCT04535258 , retrospectively registered 01.09.20.

A randomized controlled trial of a virtual reality based, approach-avoidance training program for alcohol use disorder: a study protocol.

BACKGROUND: The approach-avoidance training program (AATP) has shown preliminary promise as an add-on to standard treatment for alcohol dependence. However, knowledge is lacking as to whether the effectiveness of AATP can be enhanced further when performed in a typical drinking situation. The main aim of this study is to investigate whether approach-avoidance training implemented in a virtual reality bar environment is superior to the classical joystick PC-version of the AATP. METHODS: The study will be implemented as a randomized controlled trial. A total of 204consecutively enrolled alcohol use disorder (AUD) patients, recruited from alcohol inpatient clinics in Germany, Poland and Denmark, will be randomized into one of three groups at the start of standard alcohol treatment: group A) stimuli-relevant AATP + treatment as usual (TAU); group B) stimuli-relevant AATP in virtual reality + TAU, and group C) TAU only (control group). Treatment outcomes will be assessed at pre-treatment, post-treatment and 3-month follow-up. Repeated-measures ANOVA will be applied to compare the trajectories of the groups over time on drinking, craving and impulsiveness outcomes. It is hypothesized that the two experimental groups will achieve better treatment outcomes compared to group C and that group B will achieve better outcomes than group A. DISCUSSION: This study is the first trial examining the effectiveness of stimuli-relevant AATP delivered in a VR environment. The use of VR has shown promise in enhancing the effectiveness of other psychological treatments and since AATP has already been shown effective as add-on treatment, it is of interest to investigate whether these effects can be further enhanced by implementing the program in more ecologically valid environments. If proven effective, the AATP-VR can, like the AATP, be implemented easily and cheaply as add-on treatment or continued care to enhance the effectiveness of current evidence-based treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04283305 Registration date: 24.02.20.